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Non-alcoholic steatohepatitis (NASH) is a chronic metabolic syndrome and the CFLAR-JNK pathway can reverse the process of NASH. Although silibinin is used for the treatment of NASH in clinical, its effect on CFLAR-JNK pathway in NASH remains unclear. This study aimed to investigate the effect of silibinin on CFLAR-JNK pathway in NASH models both in vivo and in vitro . The in vivo study was performed using male C57BL/6 mice fed with methionine- choline-deficient diet and simultaneously treated with silibinin for 6 weeks. The in vitro study was performed by using mouse NCTC-1469 cells which were respectively pretreated with oleic acid plus palmitic acid, and adenovirus-down Cflar for 24 h, then treated with silibinin for 24 h. After the drug treatment, the key indicators involved in CFLAR-JNK pathway including hepatic injury, lipid metabolism and oxidative stress were determined. Silibinin significantly activated CFLAR and inhibited the phosphorylation of JNK, up-regulated the mRNA expression of Pparα, Fabp5, Cpt1α, Acox, Scd-1, Gpat and Mttp , reduced the activities of serum ALT and AST and the contents of hepatic TG, TC and MDA, increased the expression of NRF2 and the activities of CAT, GSH-Px and HO-1, and decreased the activities and expression of CYP2E1 and CYP4A in vivo . These effects were confirmed by the in vitro experiments. Silibinin prevented NASH by regulating CFLAR-JNK pathway, and thereby on one hand promoting the β -oxidation and efflux of fatty acids in liver to relieve lipid accumulation, and on the other hand inducing antioxidase activity (CAT, GSH-Px and HO-1) and inhibiting pro-oxidase activity (CYP2E1 and CYP4A) to relieve oxidative stress.

Introduction: In spite of the multiple benefits of combination antiretroviral therapy (cART) on HIV positive patients, prolonged usage has been reported to exacerbate oxidative stress, and induce neurological and cognitive dysfunction, thus, the need to search for an adjuvant therapy to ameliorate the oxidative and improve treatment adherence with better virological outcome. This study aimed at determining the potential therapeutic effects of Quercetin and Naringenin on cART-induced cyto-architectural, neuro-behavioral and immunohistochemical changes in the hippocampus of the adult Wister rats., Materials and Methods: The animals were grouped as follows: Control, DMSO, 24 mg/kg cART (Tenovovir 300 mg, Lamivudine 300 mg and Efavirenz 600 mg), 50 mg/kg Naringenin, 50 mg/kg Quercetin, cART + Naringenin, cART + Quercetin were administered orally for 8 weeks. At the end of administration, neurobehavioural test was conducted, animals were euthanized and hippocampus was processed for oxidative stress markers, histology, TNF-α, and Monoamine oxidase-B expression., Results: At the end of 8 weeks of administration, 24 mg/kg cART decreased superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and increased Malondialdehyde (MDA). Whereas, 50 mg/kg quercetin, and 50 mg/kg Naringenin decreased the oxidative stress (increased SOD, CAT, GSH, and reduced MDA) induced by cART (reduced SOD, CAT, GSH, and increased MDA). In addition, hematoxylin and eosin stained hippocampus showed that quercetin and naringenin prevented neurodegenerative changes (marked cytoplasmic shrinkage and several pyknotic nuclei in the dentate gyrus and cornus ammonis regions) in cART-treated rats. Furthermore, immunohistochemical studies revealed that quercetin and naringenin attenuates cART-induced upregulation of monoamine oxidase-B (MAO-B) expression. Likewise, from the Morris water maze neurobehavioral studies, naringenin and quercetin also ameliorated cART-induced memory impairments (initial spatial memory, reversal spatial memory and probe tests)., Conclusion: This study shows that Naringenin and Quercetin have a good potential in reversing cART-induced hippocampal disorders in Wistar rats.

Aluminum oxide nanoparticles (Al 2 O 3 NPs) and zinc oxide nanoparticles (ZnONPs) have been involved in many industries and they are extensively abundant in many aspects of human life. Consequently, concerns have been raised about their potentially harmful effects. However the toxicities of Al 2 O 3 NPs and ZnONPs are well documented, the effect of co-exposure to both nanoparticles remains strictly obscure. Therefore, the present study was undertaken to address this issue. Four groups of male Wistar rats (10 rats each) were used; control, Al 2 O 3 NPs treated, ZnONPs treated and Co-treated groups. Rats were orally administered their respective treatment daily for 75 days. The effects of each nanoparticle alone or in combination were assessed at different levels including; hepatic and renal function, structure, and redox status, nuclear DNA fragmentation, hepatic expression of mitochondrial transcription factor A (mtTFA) gene and peroxisome proliferator-activated receptor gamma-coactivator 1α (PGC-1α), systemic inflammation, and hematologic parameters. The results confirmed the hepatorenal toxicities of each nanoparticle used at the level of all parameters with suppression of the hepatic expression of mtTFA and PGC-1α. The co-exposure to both nanoparticles results in synergistic effects. From these results, we can conclude that co-exposure to aluminum oxide nanoparticles and zinc oxide nanoparticles results in more pronounced hepatorenal toxicities and systemic inflammation.

Objective: Anti-inflammatory activity of rhein in animal models with potential mechanism of actions., Methods: Rhein was isolated from Cassia fistula L. flowers collected in Chennai, Tamil Nadu, India. Its anti-inflammatory activity was then investigated in Wistar rats and mice using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, cotton pellet-induced granuloma and acetic acid-induced vascular permeability models., Results: Administration of rhein (10, 20, 40 mg/kg) significantly ( p  < 0.05) inhibited carrageenan-induced paw oedema in rats and croton oil-induced ear oedema in mice in dose-dependent manners. Continual administration of rhein to rats using implanted cotton pellets significantly ( p  < 0.05) reduced granuloma formation (20 mg/kg: 17.24%; 40 mg/kg: 36.12%) compared to control group animals. Administration of rhein increased the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and decreased the levels of nitrite, interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA) and vascular endothelial growth factor (VEGF) compared to control animals. Western blotting results revealed that rhein diminished carrageenan-induced cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and increased heme oxygenase (HO)-1, nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR)-γ and heat shock protein (HSP)-72 expression after 6 h in the paw oedema model., Conclusion: The anti-inflammatory mechanisms of rhein might be related to decrease in the levels of MDA, iNOS and COX-2 and the stimulation of HO-1, PPAR-γ and Nrf2 expression via increases in the activities of CAT, SOD and GSH-px through the suppression of nitrite, TNF-α, IL-6 and IL-1β.

Question: Donor liver organs with moderate to high fat content (i.e. steatosis) suffer from an enhanced susceptibility to ischemia/reperfusion injury (IRI) during liver transplantation. Responsible for the cellular injury is an increased level of oxidative stress, however the underlying mechanistic network is still not fully understood., Method: We developed a phenomenological mathematical model of key processes of hepatic lipid metabolism linked to pathways of oxidative stress. The model allows the simulation of hypoxia (i.e. ischemia-like conditions) and reoxygenation (i.e. reperfusion-like conditions) for various degrees of steatosis and predicts the level of hepatic lipid peroxidation (LPO) as a marker of cell damage caused by oxidative stress., Results & Conclusions: Our modeling results show that the underlying feedback loop between the formation of reactive oxygen species (ROS) and LPO leads to bistable systems behavior. Here, the first stable state corresponds to a low basal level of ROS production. The system is directed to this state for healthy, non-steatotic livers. The second stable state corresponds to a high level of oxidative stress with an enhanced formation of ROS and LPO. This state is reached, if steatotic livers with a high fat content undergo a hypoxic phase. Theoretically, our proposed mechanistic network would support the prediction of the maximal tolerable ischemia time for steatotic livers: Exceeding this limit during the transplantation process would lead to severe IRI and a considerable increased risk for liver failure.

Mitochondrial targeting is a promising approach for solving current issues in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Other moieties, including short peptides, dequalinium, guanidine, rhodamine, and F16, are also known to be promising mitochondrial targeting agents. Direct conjugation of mitochondrial targeting moieties to anticancer drugs, antioxidants and sensors results in increased cytotoxicity, anti-oxidizing activity and sensing activity, respectively, compared with their non-targeting counterparts, especially in drug-resistant cells. Although many mitochondria-targeted anticancer drug conjugates have been investigated in vitro and in vivo , further clinical studies are still needed. On the other hand, several mitochondria-targeting antioxidants have been analyzed in clinical phases I, II and III trials, and one conjugate has been approved for treating eye disease in Russia. There are numerous ongoing studies of mitochondria-targeted sensors.

Momordica charantia ( M. charantia ) is known for its antioxidant and antidiabetic properties. The aim of this study is to investigate the renoprotective effects of M. charantia in rats following treatment with highly active antiretroviral therapy (HAART) regimen triplavar. Adult male Sprague-Dawley rats weighing 178.1-220.5 g (n = 36) were divided into six groups (A-F) with each group comprising of six (n = 6) rats. The drugs and extract were administered via oral gavage. The therapeutic dose of triplavar was adjusted using the human therapeutic dose equivalent for the rat model. Animals were euthanized on the tenth week with kidneys removed for examination and blood obtained via cardiac puncture. Levels of oxidative stress enzymes (superoxide dismutase-SOD, catalase-CAT, and reduced glutathione-GSH) were significantly lowered in all groups not receiving M. charantia . The levels of thiobarbituric acid reactive substances (TBARS) were increased resulting in free radical formation via auto-oxidation. Renal parameters showed no albuminuria, normal blood urea nitrogen (BUN), serum creatinine (SCr) and electrolytes in groups treated with M. charantia . HAART treated (Group B) showed severe albuminuria, a significantly ( p < 0.05 ) raised BUN and SCr and gross electrolyte disturbances. Blood glucose levels were significantly raised in groups not receiving the adjuvant M. charantia ( p < 0.05 ). Histopathology in HAART treated animals showed glomerular capillary abnormalities and cellular infiltrations while M. charantia treated animals showed an essentially normal glomerular appearance with capillary loops and normal cytoarchitecture. In conclusion M. charantia extract administration improved blood glucose levels, restored renal histology, reinstate renal function, reduce body weight loss and restores hyperglycemia.

The aim of the study is to levels of nicotine and cotinine were elevated the oxidative stress malondialdehyde (MDA) and inflammation as nitric oxide (NO 2 and NO 3 ) may possibly be associated with decreased antioxidant enzyme activities and can sensitively indicate the production of reactive oxygen species (ROS). To evaluate the quantitative analysis of nicotine and cotinine levels and the alterations in the selected parameters of antioxidant metabolisms during nitroxidative stress in the saliva of smokeless tobacco consumers. Saliva nicotine and cotinine was measured by HPLC method and nitric oxide, lipid peroxidation and activities of antioxidant enzymes were estimated by spectrophotometric methods. Significant increase in concentrations of nicotine and cotinine levels of saliva in smokeless tobacco users in comparison to controls. Saliva lipid peroxidation was increased in experimental subjects (gutkha group 39.28% and khaini group 25.00%) as compared to controls and nitric oxide in the form of nitrites and nitrates was significantly increased in the saliva of smokeless tobacco users compared to controls. The activity levels of antioxidant enzymes were decreased in the saliva of the smokeless tobacco users in comparison with normal controls. A strong positive correlation of nicotine and cotinine with nitroxidative stress markers in gutkha and khaini users. Increased expression of inducible nitric oxide synthase (iNOS) enzyme leads to intoxication in saliva and indirectly induces inflammation process. Increased production of reactive oxygen species (ROS) and decrease in the activity levels of antioxidant enzymes in the saliva of smokeless tobacco users indicate conspicuous cell and tissue damage.

Lambda-cyhalothrin (LCT) is a synthetic pyrethroid that is widely used to control insecticide. Ginger is a traditional plant that is widely used as a spice or folk medicine. This study evaluates the antioxidant effect of ginger extract on thyroid toxicity induced by LCT in albino rats. Adult Rats were divided into 4 experimental groups: Group 1: control, Group 2: oral ginger treatment (24 mg/ml, 3 days/week for 4 weeks), Group 3: oral LCT treatment (1/100 LD 50 , 3 days/week for 4 weeks), Group 4: oral LCT and ginger mixture treatment. The histological results of LCT group showed degenerated follicles with reduced colloids, congestion of blood vessels and hyperaemia between the follicles. Histochemically, depletion of glycogen and proteins was recorded in follicular cells and colloids. The biochemical results of LCT treated group revealed a decrease in T3, T4, SOD and CAT, while TSH and MDA were increased. The comet assay showed that LCT significantly induced DNA damage in the thyroid gland. However, treating rats with LCT plus ginger led to an improvement in the histological structure of the thyroid, with noticeable increases in glycogen and protein deposition. Also, LCT plus ginger increase in T3, T4 and the antioxidant enzymes SOD and COT were detected concomitantly with a decrease in TSH and MDA as well as a significant reduction in DNA damage. LCT affected the thyroid function and structure. On the other hand, ginger has a preventative effect against the histological damage and biochemical toxicity caused by the (LCT) insecticide.

The data existing in this article are associated to the antidiabetic activity of ethyl acetate extract of Putranjiva roxburghii Wall barks (EAPR) in streptozotocin (STZ) induced diabetic rats at a dose of 250 & 500 mg/kg by oral route for 21 days. The phytochemical screening of the extract was carried out by gas chromatography and mass spectrometry. Diabetes was induced by streptozotocin (50 mg/kg; i.p), EAPR (250 & 500 mg/kg; b.wt) and standard Insulin (6 IU/animal; subcutaneous; o.i.d) were administered to the diabetic rats. Body weight and blood glucose were estimated weekly. Cholesterol, SOD and CAT were estimated in the blood serum on 21 days of the investigation period. Oral administration of EAPR (500 mg/kg) significant rises in the body weight, decrease in the blood glucose and total cholesterol and restore function of SOD and CAT enzymes ( P  < 0.05). Current data were also supported by histological study, necrosis was observed in the diabetic rat pancreas; however, necrosis was less observable in treated groups. These findings reveal that an ethyl acetate extract of Putranjiva roxburghii Wall barks shows antihyperglycemic, anti-cholesterolemic, antioxidant and improved the cell density of β-cells of islets of Langerhans in diabetic rats.

Nephrotoxicity is a major limiting factor in cisplatin treatment. In the present study hydro-ethanolic leaf extract of Emblica officinalis was investigated for its protective role in cisplatin induced nephrotoxicity. The experiment was designed for 14 days and male Wistar rats were divided into 9 groups (n = 5). Group 1 served as control (with no treatment), group 2 served as a vehicle control and received 0.9% NaCl intraperitoneally (i.p.) on 11th day of the treatment, group 3 received a single dose of cisplatin on 11th day (12 mg/kg body weight, i.p.), group 4-6 received leaf extract only (100 mg/kg, 200 mg/kg and 400 mg/kg body weight, respectively) throughout the treatment, group 7-9 received leaf extract (100 mg/kg, 200 mg/kg and 400 mg/kg body weight, respectively) throughout the treatment and single dose of cisplatin on the 11th day of the leaf extract treatment. At the end of the experiment ( i.e. on 14th day) blood samples were collected from all the groups and were sacrificed to study renal functional parameters. Treatment with above doses of E. officinalis leaf extract significantly (p ≤ 0.05) attenuates renal damage by decreasing serum creatinine and blood urea nitrogen (BUN), enhanced the activities of Catalase, SOD, GPx, GR and decreased the renal MDA level compared with the cisplatin treatment group. Furthermore the oral administration of Amla leaf extract improves histological damage and morphological changes in RBCs. Our results suggest that, leaf extract of E. officinalis may ameliorate renal damage caused by cisplatin.

Background: Moringa oleifera extract (Lam) has many antioxidant and protective properties. Objective: to investigate the antioxidant activities of Lam in counteracting the high oxidative stress caused by acute sub-lethal aluminium phosphide (AlP) intoxication in rat heart. These activities will be detected by histopathological examination and some oxidative stress biomarkers., Methods: a single sub-lethal dose of Alp (2 mg/kg body weight) was administered orally, and Lam was given orally at a dose (100 mg/kg body weight) one hour after receiving AlP to rats., Results: aluminium phosphide caused significant cardiac histopathological changes with a significant increase in malondialdehyde (MDA); lipid peroxidation marker; and a significant depletion of antioxidant enzymes (catalase and glutathione reductase). However, treatment with Lam protected efficiently the cardiac tissue of intoxicated rats by increasing antioxidants levels with slight decreasing in MDA production compared to untreated group., Conclusions: This study suggested that Moringa oleifera extract could possibly restore the altered cardiac histopathology and some antioxidant power in AlP intoxicated rats, and it could even be used as adjuvant therapy against AlP-induced cardiotoxicity.

The present study was undertaken to determine the effects of malathion exposure on oxidative stress, functional and metabolic parameters in kidney and liver of prepubertal male mice. For this reason, two separated groups of prepubertal male mice were used in this experiment. Animals were divided into two groups, group 1 served as a control and received the corn oil and group 2 was treated with 200 mg/kg body weight (b.w.) of malathion for 30 days. In result, we found that the malathion administration led to the perturbation of biochemical markers and histopathological as well as molecular damages. These changes were accompanied by an oxidative alternation which was evaluated by lipoperoxidation process and MDA production, a diminution of sulfhydril groups (-SH) content and an antioxidant enzyme activities depletion such as total superoxide dismutase (SOD) and its isoforms, catalase (CAT) and glutathione peroxidase (GPx) in both kidney and liver tissues. These changes were related with many histopathological lesions in the liver and kidney tissues. More importantly, this insecticide clearly caused a decline in the GPx-4 expression in liver as well as GPx-3 in kidney. These data suggest that prepubertal male mice exposure to malathion showed a marked deregulation of liver and kidney functions.

The capacity of plants to accumulate cadmium (Cd) is significant for phytoremediation of Cd-polluted soils. Turnips cultivated in China include species featuring high Cd accumulation and some of these plants act as Cd hyperaccumulator landraces. These plants can accumulate over 100 mg Cd kg -1 dry weight in leaves without injury. Hence, studies that explore mechanisms underlying Cd detoxification and transport in turnip plants are essential. In the present study, we compared physiological and biochemical changes in turnip leaves treated with two Cd concentrations to controls. We discovered that Cd stress significantly increased the enzymatic activities or compound contents in the antioxidant system, including members of the glutathione-ascorbic acid cycle, whereas oxidation of reactive oxygen species (ROS) remained stable. Cd treatments also increased the contents of phytochelatins as well as a number of amino acids. Based on these results, we conclude that turnips initiate a series of response processes to manage Cd treatment. First, the antioxidant system maintaining ROS homeostasis and osmotic adjustment is excited to maintain stability of cell osmotic potential. Cd is chelated into its stable form to reduce its toxicity. Cd is possibly transported to vacuoles or non-protoplasts for isolation. Amino acid synthesis may directly and indirectly play an important role in these processes. This study partly revealed physiological and biochemical mechanisms underlying turnip response to Cd stress and provides information on artificially increasing or decreasing Cd accumulation in turnips and other plants.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is associated with oxidative stress. We surmised that pharmacologic activation of NF-E2 p45-related factor 2 (Nrf2) using the acetylenic tricyclic bis(cyano enone) TBE-31 would suppress NASH because Nrf2 is a transcriptional master regulator of intracellular redox homeostasis., Methods: Nrf2 +/+ and Nrf2 -/- C57BL/6 mice were fed a high-fat plus fructose (HFFr) or regular chow diet for 16 weeks or 30 weeks, and then treated for the final 6 weeks, while still being fed the same HFFr or regular chow diets, with either TBE-31 or dimethyl sulfoxide vehicle control. Measures of whole-body glucose homeostasis, histologic assessment of liver, and biochemical and molecular measurements of steatosis, endoplasmic reticulum (ER) stress, inflammation, apoptosis, fibrosis, and oxidative stress were performed in livers from these animals., Results: TBE-31 treatment reversed insulin resistance in HFFr-fed wild-type mice, but not in HFFr-fed Nrf2-null mice. TBE-31 treatment of HFFr-fed wild-type mice substantially decreased liver steatosis and expression of lipid synthesis genes, while increasing hepatic expression of fatty acid oxidation and lipoprotein assembly genes. Also, TBE-31 treatment decreased ER stress, expression of inflammation genes, and markers of apoptosis, fibrosis, and oxidative stress in the livers of HFFr-fed wild-type mice. By comparison, TBE-31 did not decrease steatosis, ER stress, lipogenesis, inflammation, fibrosis, or oxidative stress in livers of HFFr-fed Nrf2-null mice., Conclusions: Pharmacologic activation of Nrf2 in mice that had already been rendered obese and insulin resistant reversed insulin resistance, suppressed hepatic steatosis, and mitigated against NASH and liver fibrosis, effects that we principally attribute to inhibition of ER, inflammatory, and oxidative stress.

Objectives: To review the literature and provide an updated summary on the role of reactive oxygen species (ROS) in male infertility., Methods: A review of PubMed, Cochrane review, and Web of Science databases for full-text English-language articles published between 1943 and 2017 was performed, focusing on the aetiology of ROS, physiological role of ROS on spermatic function, pathological role of ROS in infertility, evaluation of ROS, and role of antioxidants in oxidative stress., Results: ROS play a role in spermatic function and fertilisation. The literature describes both a physiological and a pathological role of ROS in fertility. A delicate balance between ROS necessary for physiological activity and antioxidants to protect from cellular oxidative injury is essential for fertility., Conclusion: Although elevated levels of ROS are implicated as a cause of infertility, there is no consensus on selecting patients to test for ROS, which test to perform, or if treatment for ROS can have a positive impact on infertility rates and pregnancy.

Background: Red-skin root disease has seriously decreased the quality and production of Panax ginseng (ginseng)., Methods: To explore the disease's origin, comparative analysis was performed in different parts of the plant, particularly the epidermis, cortex, and/or fibrous roots of 5-yr-old healthy and diseased red-skin ginseng. The inorganic element composition, phenolic compound concentration, reactive oxidation system, antioxidant concentrations such as ascorbate and glutathione, activities of enzymes related to phenolic metabolism and oxidation, and antioxidative system particularly the ascorbate-glutathione cycle were examined using conventional methods., Results: Aluminum (Al), iron (Fe), magnesium, and phosphorus were increased, whereas manganese was unchanged and calcium was decreased in the epidermis and fibrous root of red-skin ginseng, which also contained higher levels of phenolic compounds, higher activities of the phenolic compound-synthesizing enzyme phenylalanine ammonia-lyase and the phenolic compound oxidation-related enzymes guaiacol peroxidase and polyphenoloxidase. As the substrate of guaiacol peroxidase, higher levels of H 2 O 2 and correspondingly higher activities of superoxide dismutase and catalase were found in red-skin ginseng. Increased levels of ascorbate and glutathione; increased activities of l-galactose 1-dehydrogenase, ascorbate peroxidase, ascorbic acid oxidase, and glutathione reductase; and lower activities of dehydroascorbate reductase, monodehydroascorbate reductase, and glutathione peroxidase were found in red-skin ginseng. Glutathione- S -transferase activity remained constant., Conclusion: Hence, higher element accumulation, particularly Al and Fe, activated multiple enzymes related to accumulation of phenolic compounds and their oxidation. This might contribute to red-skin symptoms in ginseng. It is proposed that antioxidant and antioxidative enzymes, especially those involved in ascorbate-glutathione cycles, are activated to protect against phenolic compound oxidation.

The purpose of this study is to examine the gastrointestinal disorders after injection of vinblastine (2 mg kg -1  b.w. i.v .) in rats. Animals were divided into two equal groups: Group 1 was considered as a control group (NaCl, 0.9%). Group 2 was treated with intravenous injection of vinblastine for 7 days. Loperamide (2 mg kg -1 ) was injected in a saline solution subcutaneously to induce constipation in another group of rats during the same period. Fecal parameters of the different groups have been determined. At the end of the experiment, animals were anaesthetized and sacrificed by decapitation. The intestinal mucosa specimens were examined for lipid peroxidation, sulfhydryl groups (-SH) and protein carbonylation as well as antioxidant enzyme activities and intracellular mediators. Gastrointestinal motility was realized by the test meal (10% charcoal in 5% gum arabic). In result, statistically significant decreases in the fecal number and water content collected during 24 h were detected in the vinblastine group, but less important than loperamide control group. The animals treated with vinblastine, showed also a significant decrease (13%) of GIT, lower than that of loperamide (34%). The intestinal tissues from vinblastine-treated rats were showed a significant increase in lipoperoxydation and H 2 O 2 production as well as a significant depletion of enzymatic and non-enzymatic antioxidants. Added to that, a disruption of intracellular iron and calcium levels was observed. Therefore, the present study provide the first strong evidence that vinblastine induced numerous disruptions in gastrointestinal which are related to oxidative stress and intracellular mediators disorders.

Background: Para - Dinitrobenzene (p -DNB) is one of the isomers of dinitrobenzene which have been detected as environmental toxicants. Skin irritation and organ toxicities are likely for industrial workers exposed to p -DNB. This study evaluated the effect of sub-chronic exposure of rats to p -DNB on cellular redox balance, hepatic and renal integrity., Methods: Forty eight male Wistar rats weighing 160-180 g were administered 50, 75, 1000 and 2000 mg/kg b.wt (body weight) of p -DNB or an equivalent volume of vehicle (control) orally and topically for 14 days. After the period of treatment, the activities of kidney and liver catalase (CAT), alkaline phosphatase (ALP) and superoxide dismutase (SOD) as well as extent of renal and hepatic lipid peroxidation (LPO) were determined. Serum ALP activity and plasma urea concentration were also evaluated., Results: Compared with control animals, p -DNB -administered rats showed decrease in the body and relative kidney and liver weights as well as increased renal and hepatic hydrogen peroxide and lipid peroxidation levels accompanied by decreased superoxide dismutase and catalase activities. However, p -DNB caused a significant increase in plasma urea concentration and serum, liver and kidney ALP activities relative to control. In addition, p -DNB caused periportal infiltration, severe macro vesicular steatosis and hepatic necrosis in the liver., Conclusions: Our findings show that sub-chronic oral and sub-dermal administration of p -DNB may produce hepato-nephrotoxicity through oxidative stress.

Around the world, species from the genus Tilia are commonly used because of their peripheral and central medicinal effects; they are prepared as teas and used as tranquilizing, anticonvulsant, and analgesic agents. In this study, we provide evidence of the protective effects of organic and aqueous extracts (100 mg/kg, i.p.) obtained from the leaves of Tilia americana var. mexicana on CCl 4 -induced liver and brain damage in the rat. Protection was observed in the liver and brain (cerebellum, cortex and cerebral hemispheres) by measuring the activity of antioxidant enzymes and levels of malondialdehyde (MDA) using spectrophotometric methods. Biochemical parameters were also assessed in serum samples from the CCl 4 -treated rats. The T. americana var. mexicana leaf extracts provided significant protection against CCl 4 -induced peripheral and central damage by increasing the activity of antioxidant enzymes, diminishing lipid peroxidation, and preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-globulin (γ-GLOB), serum albumin (ALB), total bilirubin (BB), creatinine (CREA) and creatine kinase (CK), relative to the control group. Additionally, we correlated gene expression with antioxidant activity in the experimental groups treated with the organic and aqueous Tilia extracts and observed a non-statistically significant positive correlation. Our results provide evidence of the underlying biomedical properties of T. americana var. mexicana that confer its neuro- and hepatoprotective effects.

Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4 + , the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4 + T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4 + T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4 + T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

Human pluripotent stem cells, including human induced pluripotent stem cells (hiPSCs), are promising materials for regenerative medicine and cell transplantation therapy. However, tumorigenic potential of residual undifferentiated stem cells hampers their use in these therapies. Therefore, it is important to develop methods that selectively eliminate undifferentiated stem cells from a population of differentiated cells before their transplantation. In the present study, we investigated whether plasma-activated medium (PAM) selectively eliminated undifferentiated hiPSCs by inducing external oxidative stress. PAM was prepared by irradiating cell culture medium with non-thermal atmospheric pressure plasma. We observed that PAM selectively and efficiently killed undifferentiated hiPSCs cocultured with normal human dermal fibroblasts (NHDFs), which were used as differentiated cells. We also observed that undifferentiated hiPSCs were more sensitive to PAM than hiPSC-derived differentiated cells. Gene expression analysis suggested that lower expression of oxidative stress-related genes, including those encoding enzymes involved in hydrogen peroxide (H 2 O 2 ) degradation, in undifferentiated hiPSCs was one of the mechanisms underlying PAM-induced selective cell death. PAM killed undifferentiated hiPSCs more efficiently than a medium containing the same concentration of H 2 O 2 as that in PAM, suggesting that H 2 O 2 and various reactive oxygen/nitrogen species in PAM selectively eliminated undifferentiated hiPSCs. Thus, our results indicate that PAM has a great potential to eliminate tumorigenic hiPSCs from a population of differentiated cells and that it may be a very useful tool in regenerative medicine and cell transplantation therapy.

With an objective to develop Complementary and Alternative Medicine for the treatment of diabetic nephropathy, the present study investigated the protective effects of methanolic extract of Punica granatum leaves (MPGL) in streptozotocin-induced diabetic nephropathy. Diabetic nephropathy has become a leading cause of end stage renal failure worldwide. P. granatum , due to its anti-diabetic, anti-inflammatory and antioxidant activities may retard the progression of diabetic nephropathy. In this study, diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p.) in rats. STZ-diabetic rats were treated with oral doses of MPGL (100, 200 and 400 mg/kg) for 8 weeks. At the end of the experimental period, body and kidney weight and blood glucose levels were determined. Serum and urine parameters were investigated. Antioxidant enzymes and lipid peroxide levels were determined in the kidney along with histopathological examination of the same. MPGL significantly increased body weight, lowered blood glucose levels and ameliorated kidney hypertrophy index in the STZ-diabetic rats. The extract also decreased the levels of creatinine, blood urea nitrogen, total cholesterol, triglycerides, advanced glycation end products and albumin in serum and urine, respectively. MPGL significantly increased the antioxidant parameters in the kidney. Histological evaluation revealed that MPGL treated STZ-diabetic rats demonstrated reduced vacuolar degeneration of tubules; periodic acid Schiff base (PAS) positivity staining intensity in glomeruli and basement membrane thickening. Present findings provide experimental evidence that MPGL has potential antioxidant, antihyperglycemic and anti-glycation activities which might be helpful in slowing the progression of diabetic nephropathy.

Fenugreek is one of the oldest medicinal plants with exceptional medicinal and nutritional profile. Fenugreek seeds contain a substantial amount of fiber, phospholipids, glycolipids, oleic acid, linolenic acid, linoleic acid, choline, vitamins A, B1, B2, C, nicotinic acid, niacin, and many other functional elements. It may grow well under diverse and a wide range of conditions; it is moderately tolerant to drought and salinity, and can even be grown on marginal lands in profitable way. Owing to these characteristics and heavy metal remediation potential, fenugreek may well fit several cropping systems. In addition to its medicinal uses, it may serve as an excellent off-season fodder and animal food supplement. However, efforts should be initiated to develop strategies for improving its biomass production; genetic diversity among different accessions may be mapped, breeding and crop improvement programs may be initiated to improve the biomass and nutritional and functional elements. This review highlights the morphology, adaptability, nutritional constituents and associated functionality and medicinal significance of fenugreek; its ethno-historical uses, pharmacological assumptions have also been discussed. Researchable areas are also indicated to improve its production and adaptability.

Cisplatin (CP) is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO) can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally) with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p.) respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism.

The present study was designed to explore the antioxidative status and circulating biochemical markers having a potential role in the pathogenesis of ethambutol (EMB) induced toxic optic neuropathy (TON) among diabetic and non-diabetic patients. Fifty patients under complete therapy of EMB for tuberculosis were included in the present study. Inclusion criteria for patients were to receive EMB everyday during treatment, a dose of 25 mg/kg for initial 2 months and 15 mg/kg during the rest of therapy period. We conducted color vision and visual acuity test for all patients. Fifteen out of fifty EMB induced TON patients, were found to be diabetic. Color vision and visual acuity test results were evaluated for diabetic and non-diabetic as well as twenty age matched controls. The results demonstrated a significant pattern of circulating biochemical markers between the studied groups. Data regarding hematological (RBC, p value = 0.02; Hemoglobin, p value = 0.02), hepatic (total bilirubin, p value = 0.01), renal (urea, p value = 0.03; creatinine, p value = 0.007), lipid (total cholesterol, p value = 0.01; total triglycerides, p value = 0.03) and antioxidative (superoxide dismutase, p value = 0.005; glutathione, p value = 0.02; catalase, p value = 0.02) profile showed a highly significant difference among the studied groups specially patients with diabetes. Malondialdehyde (MDA) level had gone significantly up in diabetic TON patients (p value = 0.02), in comparison to other antioxidants and vitamins (Vit). Vit-A, E, B1, B12 and Zinc seem to be playing a major role in the pathogenesis of TON, specially Vit-E and B1 surpassed all the antioxidants as having highly significant inverse relationships with MDA (MDA vs Vit-E, r = -0.676(**) and MDA vs Vit-B1, r = -0.724(**) respectively). We conclude that during the ethambutol therapy the decreased levels of Vit-E and Vit-B1 possibly play a role in the development of TON and may be used as therapeutic agents to lessen the deleterious effects of ethambutol.

Catalase plays a major role in protecting cells against toxic reactive oxygen species. Here, Catalase was purified from larvae of the camel tick Hyalomma dromedarii and designated TLCAT. It was purified by ammonium sulfate precipitation and chromatography on DEAE-cellulose, Sephacryl S-300 and CM-cellulose columns. Gel filtration and SDS-PAGE of the purified TLCAT indicated that the protein has a native molecular weight of 120 kDa and is most likely a homodimer with a subunit of approximately 60 kDa. The Km value of TLCAT is 12 mM H 2 O 2 and displayed its optimum activity at pH 7.2. CaCl 2 , MgCl 2 , MnCl 2 and NiCl 2 increased the activity of TLCAT, while FeCl 2, CoCl 2 , CuCl 2 and ZnCl 2 inhibited the activity of TLCAT. Sodium azide inhibited TLCAT competitively with a Ki value of 0.28 mM. The presence of TLCAT in cells may play a role in protecting H. dromedarii ticks against oxidative damage. This finding will contribute to our understanding of the physiology of these ectoparasites and the development of untraditional methods to control them.

Arsenic is a toxic metalloid existing widely in the environment, and its removal from contaminated water has become a global challenge. The use of bacteria in this regard finds a promising solution. In the present study, Exiguobacterium sp. As-9, which is an arsenic resistant bacterium, was selected with respect to its arsenic removal efficiency. Quantification of arsenic in the water treated with bacterium showed that Exiguobacterium efficiently removed up to 99% of arsenic in less than 20 h. In order to reveal the possible effect of this bacterium in removal of arsenic from water and protecting fishes from the detrimental effects of arsenic, we initiated a range of studies on fresh water fish, Channa striata . It was observed that the fishes introduced into bacteria treated water displayed no symptoms of arsenic toxicity which was marked by a decreased oxidative damage, whereas the fishes exposed to arsenic revealed a significant ( p  < 0.05) increase in the oxidative stress together with the elevated levels of malondialdehyde. Determination of the bioaccumulation of arsenic in the liver tissues of C. striata using hydride generation atomic absorption spectrophotometry (HG-AAS) revealed an increased As(III) accumulation in the fishes exposed to arsenic whereas the arsenic level in the control and bacteria treated fishes were found below the detectable limit. In conclusion, this study presents the strategies of bacterial arsenic removal with possible directions for future research.

Purpose: Production of reactive oxygen species and reactive nitrogen species is a natural biological event in metabolism. However, the presence of antioxidants can highly reduce the negative effect of free radicals. Thus, the efficiency of antioxidant system in the physiology of exercise is very important., Design: Considering the known antioxidant capacity of garlic, the purpose of this study was to evaluate the effect on combining 14 days aerobic exercise till exhaustion with garlic extract supplementation on the antioxidant capacity of saliva., Methods: Sixteen young men volunteered to participate in this randomized, double blind, placebo-controlled study and were randomly placed into two groups, placebo (Group I) and garlic extract (Group II). The participants performed exhaustive aerobic exercise on a treadmill before and after supplementation. Their unstimulated salivary samples were collected before, immediately after, and 1 h after the activity. The antioxidant activity in terms of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) was then measured in the collected samples using their specific substrates., Results: A significant increase in salivary antioxidant activity of SOD, POD, and CAT was observed in saliva of the supplement group compared to the placebo group (P ≤ 0.05)., Conclusion: The findings from this study suggest that increased activity of antioxidant enzymes could possibly decrease exercise-induced oxidative damage in male athletes.

High temperature is one of the prominent environmental factors causing economic losses to the poultry industry as it negatively affects growth and production performance in broiler chickens. We used One Step TaqMan real time RT-PCR (reverse transcription polymerase chain reaction) technology to study the effects of chronic heat stress on the expression of genes codifying for the antioxidative enzymes superoxide dismutase (SOD), and catalase (CAT), as well as for heat shock protein (HSP) 70, HSP90, glucocorticoid receptor (NR3C1), and caspase 6 (CASP6) in the liver of two different broiler genetic strains: Red JA Cou Nu Hubbard (CN) and Ross 508 Aviagen (RO). CN is a naked neck slow growing broiler intended for the free range and/or organic markets, whereas RO is selected for fast growing. We also analysed the effect of chronic heat stress on productive performances, and plasma corticosterone levels as well as the association between transcriptomic response and specific SNPs (single nucleotide polymorphisms) in each genetic strain of broiler chickens. RO and CN broilers, 4 weeks of age, were maintained for 4 weeks at either 34 °C or 22 °C. The results demonstrated that there was a genotype and a temperature main effect on the broilers' growth from the 4th to the 8th week of age, but the interaction effect between genotype and temperature resulted not statistically significant. By considering the genotype effect, fast growing broilers (RO) grew more than the slow growing ones (CN), whereas by considering the temperature effect, broilers in unheated conditions grew more than the heat stressed ones. Corticosterone levels increased significantly in the blood of heat stressed broilers, due to the activation of the HPA (hypothalamic-pituitary-adrenocortical axis). Carcass yield at slaughter was of similar values in the 4 cohorts (genotype/temperature combinations or treatment groups), ranging from 86.5 to 88.6%, whereas carcass weight was negatively influenced by heat stress in both broiler strains. Heat stress affected gene expression by downregulating CASP6 and upregulating CAT transcript levels. HSPs, SOD and NR3C1 mRNA levels remained unaffected by heat stress. The differences found in the mRNA copies of CASP6 gene could be partly explained by SNPs.

The aim of the present study was to isolate hepatoprotective component from Urtica dioica Linn. (whole plant) against CCl 4 -induced hepatotoxicity in-vitro (HepG2 cells) and in-vivo (rats) model. Antioxidant activity of hydro alcoholic extract and its fractions petroleum ether fraction (PEF), ethyl acetate fraction (EAF), n -butanol fraction (NBF) and aqueous fraction (AF) were determined by DPPH and NO radicals scavenging assay. Fractions were subjected to in-vitro HepG2 cell line study. Further, the most potent fraction (EAF) was subjected to in-vivo hepatoprotective potential against CCl 4 challenged rats. The in-vivo hepatoprotective active fraction was chromatographed on silica column to isolate the bioactive constituent(s). Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1 H NMR, 13 C NMR and MS spectroscopy. Ethyl acetate fraction (EAF) of hydro-alcoholic extract of U. dioica possessed the potent antioxidant activity viz. DPPH (IC 50 78.99 ± 0.17 μg/ml) and NO (IC 50 101.39 ± 0.30 μg/ml). The in-vitro HepG2 cell line study showed that the EAF prevented the cell damage. The EAF significantly attenuated the increased liver enzymes activities in serum and oxidative parameters in tissue of CCl 4 -induced rats, suggesting hepatoprotective and anti-oxidant action respectively. Column chromatography of most potent antioxidant fraction (EAF) lead to the isolation of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid) which is responsible for its hepatoprotective potential. Hence, the present study suggests that EAF of hydro-alcoholic extract has significant antioxidant and hepatoprotective potential on CCl 4 induced hepatotoxicity in-vitro and in-vivo .

Erectile dysfunction (ED) affected the lives of more than 300 million men worldwide. Erectile dysfunction drugs (EDD), known as phosphodiesterase inhibitors (PDEIs), have been used for treatment of ED. It has been shown that oxidative stress plays an important role in the progression of erectile dysfunction. Oxidative stress can be alleviated or decreased by antioxidant enzymes. Therefore, the present study aims at investigating the changes in the activity of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione reductase as well as protein expression of glutathione peroxidase and glutathione S -transferase after treatment of male rats with a daily dose of sildenafil (1.48 mg/kg), tadalafil (0.285 mg/kg) and vardenafil (0.285 mg/kg) for three weeks. In addition, levels of reduced glutathione and malondialdyhyde (MDA) were assayed. The present study showed that sildenafil, vardenafil, and tadalafil treatments significantly decreased the levels of glutathione, MDA and the activity of glutathione reductase. In addition, vardenafil and sildenafil increased the activity of superoxide dismutase and catalase. Interestingly, western immunoblotting data showed that vardenafil induced the activity of glutathione peroxidase (GP X ) and its protein expression, whereas tadalafil and sildenafil inhibited such enzyme activity and its protein expression. In addition, the protein expression of GST π isozyme was markedly reduced after treatment of rats with sildenafil. It is concluded that ED drugs induced the activities of both SOD and catalase which consequently decreased MDA level. Therefore, decrement in MDA levels could increase nitric oxide-cGMP level which in turn promotes the erection mechanism.

4-Nitrophenol (PNP), is generally regarded as an environmental endocrine disruptor (EED). Phytosterin (PS), a new feed additive, possesses highly efficient antioxidant activities. The transcription factor, nuclear factor-erythroid 2-related factor 2 (Nrf2), is an important regulator of cellular oxidative stress. Using rats, this study examined PNP-induced testicular oxidative damage and PS-mediated protection against that damage. The generation of MDA and H 2 O 2 upon PNP and PS treatment was milder than that upon treatment with PNP alone. This mitigation was accompanied by partially reversed changes in SOD, CAT, GSH and GSH-Px. Moreover, PNP significantly reduced the caudal epididymal sperm counts and serum testosterone levels. Typical morphological changes were also observed in the testes of PNP-treated animals. PNP reduced the transcriptional level of Nrf2, as evaluated by RT-PCR, but it promoted the dissociation from the Nrf2 complex, stabilization and translocation into the nucleus, as evaluated by immunohistochemistry and Western blotting. In addition, PNP enhanced the Nrf2-dependent gene expression of heme oxygenase-1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC). These results suggest that the Nrf2 pathway plays an important role in PNP-induced oxidative damage and that PS possesses modulatory effects on PNP-induced oxidative damage in rat testes.

Background and Aim: It is recognized that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), may develop after pancreaticoduodenectomy (PD). However, the mechanism of NASH development remains unclear. This study aimed to examine the changes in gene expression associated with NASH occurrence following PD., Methods: The expression of genes related to fatty acid/triglyceride (FA/TG) metabolism and inflammatory signaling was examined using liver samples obtained from 7 post-PD NASH patients and compared with 6 healthy individuals and 32 conventional NASH patients., Results: The livers of post-PD NASH patients demonstrated significant up-regulation of the genes encoding CD36, FA-binding proteins 1 and 4, acetyl-coenzyme A carboxylase α, diacylglycerol acyltransferase 2, and peroxisome proliferator-activated receptor (PPAR) γ compared with normal and conventional NASH livers. Although serum apolipoprotein B (ApoB) and TG were decreased in post-PD NASH patients, the mRNAs of ApoB and microsomal TG transfer protein were robustly increased, indicating impaired TG export from the liver as very-low-density lipoprotein (VLDL). Additionally, elevated mRNA levels of myeloid differentiation primary response 88 and superoxide dismutases in post-PD NASH livers suggested significant activation of innate immune response and augmentation of oxidative stress generation., Conclusions: Enhanced FA uptake into hepatocytes and lipogenesis, up-regulation of PPARγ, and disruption of VLDL excretion into the circulation are possible mechanisms of steatogenesis after PD., General Significance: These results provide a basis for understanding the pathogenesis of NAFLD/NASH following PD.

Curcumin (CUR) is a highly pleiotropic molecule and possesses anti-inflammatory, hypoglycemic, antioxidative, wound-healing and antimicrobial activities. The present study was carried out to investigate whether CUR plays any beneficial role in streptozotocin (STZ) induced hepatic pathophysiology in diabetic rats. STZ exposure increased hepatic damage associated serum markers (ALT, ALP and LDH) as well as NO production in the liver tissue. Moreover, the same exposure enhanced ROS generation and lipid peroxidation; reduced GSH levels and antioxidant enzyme activities. Hyperglycemia induced hepatic pathophysiology also activated stress response pathways (involving phosphorylation of p38, ERK1/2 MAPKs and p53) and reduced mitochondrial membrane potential which in turn led to cellular apoptosis as evidenced from increased hepatic DNA fragmentation as well as FACS analysis. However, treatment with CUR effectively counteracts diabetes-induced, oxidative stress mediated hepatic damage and could act as a therapeutic in lessening liver dysfunction in diabetic subjects.

Ascorbate (AsA)-glutathione (GSH) cycle metabolism has been regarded as the most important defense mechanism for the resistance of plants under stress. In this study the influence of salicylic acid (SA) was studied on ascorbate-glutathione pathway, S-assimilation, photosynthesis and growth of mustard (Brassica juncea L.) plants subjected to 100 mM NaCl. Treatment of SA (0.5 mM) alleviated the negative effects of salt stress and improved photosynthesis and growth through increase in enzymes of ascorbate-glutathione pathway which suggest that SA may participate in the redox balance under salt stress. The increase in leaf sulfur content through higher activity of ATP sulfurylase (ATPS) and serine acetyl transferase (SAT) by SA application was associated with the increased accumulation of glutathione (GSH) and lower levels of oxidative stress. These effects of SA were substantiated by the findings that application of SA-analog, 2,6, dichloro-isonicotinic acid (INA) and 1 mM GSH treatment produced similar results on rubisco, photosynthesis and growth of plants establishing that SA application alleviates the salt-induced decrease in photosynthesis mainly through inducing the enzyme activity of ascorbate-glutathione pathway and increased GSH production. Thus, SA/GSH could be a promising tool for alleviation of salt stress in mustard plants.

Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage.

α-Cypermethrin is a widely used insecticide and, at high doses, induces oxidative stress in mammals. Curcumin is an antioxidant phytochemical commonly used for food coloring and flavoring. We aimed to investigate the effects of continuous dietary exposure to low doses of α-cypermethrin, as is the case in exposed humans, on oxidative stress and its potential prevention by dietary curcumin. Four groups of ten male Wistar rats were ad libitum-fed a control diet or identical diets fortified with α-cypermethrin (350 mg/kg diet), curcumin (1000 mg/kg diet), or α-cypermethrin and curcumin (350 and 1000 mg/kg diet, respectively) for 7 weeks. α-Cypermethrin accumulated in adipose tissues and was detectable in kidney, liver, and brains. Dietary α-cypermethrin did not alter concentrations of malondialdehyde, ascorbic and uric acid, retinol, liver damage markers, or the activities of CAT and SOD, but reduced vitamin E in blood. α-Cypermethrin did not affect malondialdehyde or reduced glutathione concentrations in any of the tissues, but significantly increased glutathione disulfide in kidney and subcutaneous adipose tissue. In conclusion, dietary exposure to small doses of α-cypermethrin did not induce oxidative stress in rats and may be less toxic than exposure to comparable quantities administered as single high doses by gastric intubation.

Monosodium glutamate (MSG) has been recognized as flavor enhancer that adversely affects male reproductive systems. The present study was carried out to evaluate the potential protective role of vitamin E (vit E) or selenium against MSG induced oxidative stress and histopathological changes in testis tissues of rats. Mature male Wistar rats weighing 150-200 g BW were allocated to evenly twelve groups each group of ten animals, the first group was maintained as control group, the 2nd, 3rd and 4th groups were administered MSG in three different dose levels (low, medium and high) (6, 17.5 and 60 mg/kg BW), the 5th and 6th groups were given vit E in two doses (low and high) (150 and 200 mg/kg), the 7th and 8th groups were administered selenium in two doses (low and high) (0.25 and 1 mg/kg) daily via gavage for a period of 30 days. Meanwhile the 9th and 10th groups were given combinations of MSG (high dose) and vit E while, the 11th and 12th groups were given MSG (high dose) plus selenium in two recommended doses for each one. Monosodium glutamate caused an elevation in lipid peroxidation level parallel with significant decline in SOD, CAT as well as GPx activities in testis tissues. Administration of vit E or selenium to MSG-treated groups declined lipid peroxidation, increased SOD, CAT, GPx activities. Selenium or vit E significantly reduced MSG induced histopathological changes by the entire restoration of the histological structures and the testicular antioxidant status to great extent in treated rats. In conclusion, supplementation of selenium or vit E could ameliorate the MSG induced testicular toxicity to great extent and reduce the oxidative stress on testis tissues.

Several epidemiological studies have reported the relation between chromium exposure (used in different industrial processes) and cancer risk. Evidence indicates that the hexavalent form is mutagenic and carcinogenic. Chemoprevention has emerged as a good strategy for reducing the risk from exposure to heavy metals. There is evidence that some tetrapyrrols such as protoporphyrin IX (PP-IX), a porphyrin without a metal center and which is a precursor of hemoglobin and cytochrome, acts as an antioxidant modulating the induction of antioxidant enzymes. The present study was performed to evaluate their antimutagenic potential of PP-IX against genetic damage induced by chromium trioxide (CrO 3 ). The wing spot test was used. Groups of 48 h-old larvae were pretreated for 24 h with 0, 0.69, 6.9, or 69 mM of PP-IX, after which groups of larvae were fed 0.025-2.5 mM CrO 3 solution in Drosophila instant medium. The results indicated that the lower PP-IX concentration (0.69 mM) significantly reduced the genetic damage induced by all CrO 3 concentrations tested. In contrast, 6.9 and 69 mM only inhibited the damage induced by CrO 3 2.5 mM. Absence of an inhibitor effect of PP-IX against 20 Gy gamma rays suggested that this porphyrin acted primarily by forming complexes with chromium at low doses, inactivating its genotoxic action rather than capturing or inactivating the reactive oxygen species generated by the chromium.

The accumulation of advanced glycation end products (AGE) plays significant role in developing tubular hypertrophy during diabetic nephropathy (DN). Reactive oxygen species and nitric oxide (NO) are directly involved in the progression of DN. We have studied the effect of standardized Gymnemasylvestre organic extract (GE) on AGE induced cellular hypertrophy using rat renal tubular epithelial cells (NRK 52E). AGE (400 μg/ml) induced cytotoxicity to NRK 52E cells as determined by MTT assay at 0-72 h. We report cellular hypertrophy mediated cytotoxicity by AGE which was the result of significant reduction in the cellular nitric oxide and cGMP levels associated with increased lipid peroxidation and antioxidant depletion ( P < 0.05). Upon treatment with GE the cell viability was increased with reduced cellular hypertrophy by 1.7 folds when compared to AGE treated group. GE could significantly increase NO by 1.9 folds and cGMP by 2.8 folds and inhibited GSH depletion by 50% during AGE induced toxicity. The antioxidant enzyme activity of catalase was increased by 50% while, glutathione peroxidase and superoxide dismutase enzyme activities were significantly increased by 42% and 67% with decreased lipid peroxidation (49%) upon GE treatment. Thus, GE attenuates AGE induced hypertrophic growth by inhibiting GSH depletion and partly through increased NO/cGMP signaling.

The present study investigated the possible protective role of Withania somnifera (Linn.) Dunal (Solanaceae) root powder against bromobenzene-induced oxidative damage in rat liver mitochondria. Administration of bromobenzene (10 mmol/kg body weight) to rats resulted in increased levels of liver marker enzymes, lipid peroxidation, TNF-α, IL-1β and VEGF. There was also marked depletion in the levels of mitochondrial enzymes and antioxidant activity. Pre-treatment with W. somnifera significantly decreased the levels of liver marker enzymes, TNF-α, IL-1β, VEGF and ameliorated histopathological manifestations in bromobenzene-treated rats. The molecular docking analysis predicted that the pro-inflammatory mediator NF-κB showed significant interaction with selected various active components of W. somnifera (withaferin A, withanolide D and withanolide E). This study demonstrates a good protective effect of W. somnifera against bromobenzene-induced oxidative stress.

A plant regeneration protocol was devised for Cardiospermum halicacabum by means of aseptically extracted 7 days old hypocotyls forming adventitious shoots on Murashige and Skoog (MS) medium harmonized with 0.7 μM thidiazuron (TDZ) producing a maximum of 18.20 ± 0.98 number of shoots in 94% cultures following 4 weeks. Subsequent subculturing for five passages, on a medium without plant growth regulators, tempted the highest shoot number (40.00 ± 1.15) with an average shoot length of 6.53 ± 0.49 cm after the fourth subculture. Histological sections confirmed the formation of multiple buds from hypocotyl explants. The expression of antioxidant enzymes like superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase was found to be higher in acclimatized plants than in the in vitro cultured ones suggesting the involvement of these enzymes in shoot differentiation and in growth under external environment partly due to their ability to cope up with oxidative stress.

Diabetic complications cause noticeable liver damage, which finally progresses to diabetic hepatopathy. Nutritive antioxidants not only reduce the liver damage, but also prevent it by modulating the release of various proteins involved in apoptotic signaling cascades. This study explores the molecular mechanisms underlying diabetes-induced liver damage and its modulation by naringenin. Antioxidant status, liver & kidney biomarker enzymes, reactive oxygen species (ROS) generation, mitochondrial membrane potential, expression of apoptotic proteins like Bax (bcl-2 associated X), Bcl-2 (b-cell Lymhoma-2), Caspase-3, Caspase-9, AIF (Apoptosis inducing factor) and Endo-G (Endonuclease-G) were studied in streptozotocin induced diabetic rats. Significant hyperglycemia, disturbed antioxidant status, altered carbohydrate metabolizing enzymes, increased ROS and lipid peroxidation; decreased mitochondrial membrane potential and enhanced release of AIF and Endo-G were observed. Hyperglycemia also affected apoptosis and its related genes at both transcriptional and translational level (Caspase-3 & 9, Bax and Bcl-2) in the liver of diabetic rats. Naringenin, a flavonone, exerted anti-hyperglycemic effect and was able to prevent oxidative stress and resultant apoptotic events caused due to diabetes-induced hepatotoxicity. Thus, our study shows, a protective effect of naringenin against diabetes induced liver damage and redox imbalance, which could further be exploited for the management of diabetic hepatopathy.

Bisphenol A (BPA) safety aspects on human health are debated extensively for long time. In the present study, we have studied the toxicity induced by BPA at no observed adverse effect level (NOAEL) using HepG2 cells. We report that BPA at 100 nM induced cytotoxicity to HepG2 cells as determined by MTT assay at 0-72 h. The toxicity was result of reduced oxygen consumption and reduced mitochondrial membrane potential associated with decreased ATP production. The BPA treatment resulted in increase of malondialdehyde (MDA) content with decreased glutathione and other antioxidant enzymes. BPA derived toxicity is a concern to human health and alternative non-toxic natural products/derivatives or adjuvants that serve as antidote will be relevant. In this context, Ashwagandha ( Withania somnifera) a widely used herb to treat arthritis, rheumatism and to improve longevity for time immemorial is investigated for its antidote effect. Ashwagandha supercritical CO 2 extract derived Withanolides (ADW) at 100 μg/ml protect HepG2 cells from BPA induced toxicity by suppressing mitochondrial damage and increased ATP production. Further, cellular MDA content was significantly suppressed with increased non-enzymic and antioxidant enzyme activities. These findings derived from the present study suggest the beneficial effect of ADW in mitigating BPA induced mitochondrial toxicity in HepG2 cells.

Fluoride intoxication generates free radicals, causing oxidative stress that plays a critical role in the progression of nephropathy. In the present study, we hypothesized that epigallocatechin gallate (EGCG), found in green tea, protects the kidneys of rats treated with fluoride by preventing oxidative stress, inflammation, and apoptosis. Pretreatment of fluoride-treated rats with EGCG resulted in a significant normalization of creatinine clearance and levels of urea, uric acid, and creatinine. Fluoride intoxication significantly increased renal oxidative stress markers and decreased the levels of renal enzymatic and non-enzymatic antioxidants. In addition, renal NO, TNF-α, IL-6 and NF-κB were also increased in the renal tissue of fluoride-treated rats. Further, EGCG pretreatment produced a significant improvement in renal antioxidant status and reduced lipid peroxidation, protein carbonylation and the levels of inflammatory markers in fluoride-treated kidney. Similarly, mRNA and protein analyses showed that EGCG pretreatment normalized the renal expression of Nrf2/Keap1 and its downstream regulatory proteins in fluoride-treated rat kidney. EGCG also effectively attenuated fluoride-induced renal apoptosis by the up-regulation of anti-apoptotic proteins such as Bcl-2 and down-regulation of Bax, caspase-3, caspase-9 and cytochrome c. Histology and immunohistochemical observations of Kim-1 provided further evidence that EGCG effectively protects the kidney from fluoride-mediated oxidative damage. These results suggest that EGCG ameliorates fluoride-induced oxidative renal injury by activation of the Nrf2/HO-1 pathway.

Shifts in intracellular Reactive Oxygen Species (ROS) have been shown to contribute to carcinogenesis and to tumor progression. In addition to DNA and cell damage by surges in ROS, sub-lethal increases in ROS are implicated in regulating cellular signaling that enhances pro-metastatic behavior. We previously showed that subtle increases in endogenous H2O2 regulate migratory and invasive behavior of metastatic bladder cancer cells through phosphatase inhibition and consequential phosphorylation of p130cas, an adapter of the FAK signaling pathway. We further showed that enhanced redox status contributed to enhanced localization of p130cas to the membrane of metastatic cells. Here we show that this signaling complex can similarly be induced in a redox-engineered cell culture model that enables regulation of intracellular steady state H2O2 level by enforced expression of superoxide dismutase 2 (Sod2) and catalase. Expression of Sod2 leads to enhanced p130cas phosphorylation in HT-1080 fibrosarcoma and UM-UC-6 bladder cancer cells. These changes are mediated by H2O2, as co-expression of Catalase abrogates p130cas phosphorylation and its interaction with the adapter protein Crk. Importantly, we establish that the redox environment influence the localization of the tumor suppressor and phosphatase PTEN, in both redox-engineered and metastatic bladder cancer cells that display endogenous increases in H2O2. Importantly, PTEN oxidation leads to its dissociation from the plasma membrane. This indicates that oxidation of PTEN not only influences its activity, but also regulates its cellular localization, effectively removing it from its primary site of lipid phosphatase activity. These data introduce hitherto unappreciated paradigms whereby ROS can reciprocally regulate the cellular localization of pro- and anti-migratory signaling molecules, p130cas and PTEN, respectively. These data further confirm that altering antioxidant status and the intracellular ROS environment can have profound effects on pro-metastatic signaling pathways.

In the current work, we investigated the effects of dopamine, an neurotransmitter found in several plant species on antioxidant enzyme activities and ROS in soybean (Glycine max L. Merrill) roots. The effects of dopamine on SOD, CAT and POD activities, as well as H2O2, O2(•-), melanin contents and lipid peroxidation were evaluated. Three-day-old seedlings were cultivated in half-strength Hoagland nutrient solution (pH 6.0), without or with 0.1 to 1.0 mM dopamine, in a growth chamber (25°C, 12 h photoperiod, irradiance of 280 μmol m(-2) s(-1)) for 24 h. Significant increases in melanin content were observed. The levels of ROS and lipid peroxidation decreased at all concentrations of dopamine tested. The SOD activity increased significantly under the action of dopamine, while CT activity was inhibited and POD activity was unaffected. The results suggest a close relationship between a possible antioxidant activity of dopamine and melanin and activation of SOD, reducing the levels of ROS and damage on membranes of soybean roots.

The presence of amyloid aggregates of human islet amyloid polypeptide (hIAPP), a hallmark of type 2 diabetes, contributes to pancreatic β-cell impairment, where oxidative stress plays a key role. A contribution of NADPH oxidase to reactive oxygen species (ROS) generation after cell exposure to micromolar concentrations of hIAPP aggregates has been suggested. However, little is known about β-cells exposure to lower amounts of hIAPP aggregates, similar to those found in human pancreas. Thus, we aimed to investigate the events resulting from RIN-5F cells exposure to nanomolar concentrations of toxic hIAPP aggregates. We found an early and transient rise of NADPH oxidase activity resulting from increased Nox1 expression following the engagement of receptor for advanced glycation end-products (RAGE) by hIAPP aggregates. Unexpectedly, NADPH oxidase activation was not accompanied by a significant ROS increase and the lipoperoxidation level was significantly reduced. Indeed, cell exposure to hIAPP aggregates affected the antioxidant defences, inducing a significant increase of the expression and activity of catalase and glutathione peroxidase. We conclude that exposure of pancreatic β-cells to nanomolar concentrations of hIAPP aggregates for a short time induces an hormetic response via the RAGE-Nox1 axis; the latter stimulates the enzymatic antioxidant defences that preserve the cells against oxidative stress damage.

This article provides a succinct but limited overview of the protective and deleterious effects of reactive oxygen and nitrogen species in a clinical context. Reactive oxygen species include superoxide, hydrogen peroxide, single oxygen and lipid peroxides. Reactive nitrogen species include species derived from nitric oxide. This review gives a brief overview of the reaction chemistry of these species, the role of various enzymes involved in the generation and detoxification of these species in disease mechanisms and drug toxicity and the protective role of dietary antioxidants. I hope that the graphical review will be helpful for teaching both the first year medical and graduate students in the U.S. and abroad the fundamentals of reactive oxygen and nitrogen species in redox biology and clinical medicine.