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Many xenobiotics are known to cause hepatic damage with subsequent significant morbidity and mortality. Doxorubicin (DOX) is a broad-spectrum antineoplastic agent. DOX is reported to cause hepatocellular damage. Previous studies verified the promising role of many natural antioxidant products against various models of hepatic dysfunction. We conducted this study to evaluate the possible hepatoprotective effect of silymarin (SILY) and/or chlorogenic acid (CGA) in a rat model of DOX-induced hepatotoxicity. For this purpose, we randomly divided 30 adult male rats into five equal groups as control, DOX, co-treated DOX with SILY, co-treated DOX with GCA and co-treated DOX with SILY and CGA groups. All treatments were administered every second day for 4 weeks. Our results showed that simultaneous SILY and CGA administration caused a significant decrease in hepatic apoptosis biomarkers (hepatic caspase-3 and nuclear factor-κB levels), a significant improvement in hepatic oxidant/antioxidant status (malondialdehyde and superoxide dismutase) and significant decrease in hepatic pro-inflammatory biomarkers (tumor necrosis factor-alpha and interlukin-1β) compared with DOX treatment. We concluded that adding CGA to SILY acts as a hepatoprotective agent against DOX-induced liver injury through inhibiting apoptosis biomarkers, maintaining antioxidant enzyme levels, decreasing pro-inflammatory cytokines as well as regulating liver adenosine monophosphate-activated protein kinase signaling.

Cyclophosphamide (CP) is one of the most potent alkylating agents and is widely used in the treatment of numerous neoplastic conditions, autoimmune diseases and following organ transplantation. Due to its ability to induce oxidative stress and subsequent apoptosis, CP is affiliated with many adverse effects with special emphasis on the highly prevalent hepatotoxicity. Dipeptidyl peptidase 4 (DDP-IV) inhibitors are being rediscovered for new biological effects due to their ability to target multiple pathways, among which is the phosphoinositide 3–kinase (PI3K) and protein kinase B (Akt) axis. This could offer protection to multiple organs against reactive oxygen species (ROS) through modulating sirtuin 1 (SIRT1) expression and, in turn, inactivation of forkhead box transcription factor of the O class 1 (FoxO1), thus inhibiting apoptosis. Accordingly, the current study aimed to investigate the potential therapeutic benefit of alogliptin (Alo), a DPP-IV inhibitor, against CP-induced hepatotoxicity through enhancing PI3K/Akt/SIRT1 pathway. Forty male Wistar rats were randomly divided into four groups. The CP-treated group received a single dose of CP (200 mg/kg; i.p.). The Alo-treated group received Alo (20 mg/kg; p.o.) for 7 days with single CP injection on Day 2. Alo successfully reduced hepatic injury as witnessed through decreased liver function enzymes, increased phospho (p)-PI3K, p-Akt, superoxide dismutase (SOD) levels, SIRT1 expression, p-FoxO1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2). This resulted in decreased apoptosis, as witnessed through decreased caspase-3 levels and improved histopathological picture. In conclusion, the current study succeeded to elaborate, for the first time, the promising impact of Alo in ameliorating chemotherapy-induced liver injury.

Present study was planned to investigate the ameliorative effect of silver nanoparticles (AgNPs) on acetaminophen-induced nephrotoxicity. Our results demonstrate that therapy of AgNPs at three different doses (50, 100 and 150 μg/kg once only) prevented the acetaminophen (2 g/kg once only) induced acute renal toxicity. AgNPs treated animals also show less intensity in the histological alterations in kidneys and corroborating the results of analysis of serum urea and creatinine. In addition, AgNPs therapy prevented the acetaminophen-induced oxidative stress, which was confirmed by the alleviated lipid peroxidation, enhanced renal reduced glutathione content and restored enzymatic activities of superoxide dismutase, catalase and adenosine triphosphatase in kidney. Thus, our results demonstrate a possible protective potential of AgNPs on renal toxicity induced by acetaminophen. This study will definitely lead to the development of therapeutic drug against nephrotoxicity, after further clinical and preclinical studies.

Nickel (Ni) is an essential yet toxic trace element. Although a cofactor for many metalloenzymes, nickel function and metabolism is not fully explored in eukaryotes. Molecular biology and metallomic methods were utilized to explore the new physiological functions of nickel in Saccharomyces cerevisiae. Here we showed that MTM1 knockout cells displayed much stronger nickel tolerance than wild-type cells and mitochondrial accumulations of Ni and Fe of mtm1Δ cells dramatically decreased compared to wild-type cells when exposed to excess nickel. Superoxide dismutase 2 (Sod2p) activity in mtm1Δ cells was severely attenuated and restored through Ni supplementation in media or total protein. SOD2 mRNA level of mtm1Δ cells was significantly higher than that in the wild-type strain but was decreased by Ni supplementation. MTM1 knockout afforded resistance to excess nickel mediated through reactive oxygen species levels. Meanwhile, additional Ni showed no significant effect on the localization of Mtm1p. Our study reveals the MTM1 gene plays an important role in nickel homeostasis and identifies a novel function of nickel in promoting Sod2p activity in yeast cells.

We investigated the ameliorative effect of the curcumin against methomyl-induced potential nephrotoxicity in Wistar albino male rats. In the present study, curcumin (100 mg kg−1 bw), methomyl (0,8 mg kg−1 bw) and methomyl plus curcumin were given to rats by oral for 28 days (for subacute examination). Concentrations of blood urea nitrogen, uric acid and creatinine in serum and malondialdehyde level and activities of antioxidant enzyme (superoxide dismutase, catalase, glutathione peroxidase and glutathione S transferase) and histopathological alterations in kidney tissues were studied. Methomyl caused an increment in the concentrations of blood urea nitrogen, creatinine, uric acid and MDA levels. In addition, methomyl caused a diminution in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S transferase. Tubular and glomerular degenerations occurred in the kidney tissues of methomyl-received rats. However, coadministration of curcumin with methomyl significantly minimized the adverse effects of methomyl on kidney function parameters, lipid peroxidation and antioxidant enzyme activities and histological structure of kidney tissue. The results showed that curcumin significantly mitigated methomyl-induced nephrotoxicity in rats.

Toxicities linked with Benzo (a) pyrene B[a]P exposure, particularly in liver and kidney have been reported in both animals and humans. Taurine (2-aminoethane sulfonic acid) is an intracellular β-amino acid reported to elicit hepatorenal protective functions. However, the modulatory effect of taurine on hepatorenal toxicity associated with exposure to B[a]P has not been reported. This study evaluated the effects of taurine on the hepatorenal toxicities induced in cohorts of rats exposed to B[a]P. Experimental rats were treated as follows: B[a]P (10 mg/kg); co-treated cohorts –B[a]P (10 mg/kg) plus taurine (100 or 200 mg/kg) for 4 successive weeks. Results show that co-dosing with taurine significantly (P

Arsenic (As) is a ubiquitous environmental and industrial toxin with known correlates of oxidative stress and cognitive deficits in the brain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that represents a central cellular antioxidant defense mechanism and transcribes many antioxidant genes. Peroxisome proliferator-activated receptor-gamma (PPARγ) is a well-known nuclear receptor to regulate lipid metabolism in many tissues, and it has been also associated with the control of oxidative stress, neuronal death, neurogenesis and differentiation. The role of Nrf2 and PPARγ in As-induced neurotoxicity is still debated. The present study was designed to investigate the neurobehavioral toxic effect of sub-chronic and middle-dose sodium arsenite exposure in mice hippocampus, as well as the response of Nrf2/PPARγ expression and influence on protein expression levels of their downstream antioxidant genes. Our results showed that mice treated with intraperitoneal injection of sodium arsenite (50 mg/kg body wt.) twice a week for 7 weeks resulted in increased generation of reactive oxygen species and impairment of spatial cognitive function. The present study also found a positive association between Nrf2/PPARγ expression in hippocampus of mice, and activation of antioxidant defenses by the evidently upregulated expression of their downstream genes, including superoxide dismutase, heme oxygenase-1 and glutathione peroxidase-3. Therefore, our findings were helpful for further understanding the role of Nrf2/PPARγ feedback loop in As-induced neurobehavioral toxicity.

The aromatic compounds substituted with sulfonate groups, being xenobiotic, resist biodegradation in the environment and tend to accumulate up to toxic levels. The hydrophilic sulfonated group makes these compounds highly water soluble and they tend to pass through water-treatment plants. The release of untreated effluents from these industries results in pollution of water bodies affecting aquatic fauna. Thus, the toxicity regarding these compounds is of major concern. The 2-naphthalene sulfonate is a sulfonated aromatic compound being widely used in textile industries. Being non-biodegradable concern regarding its toxicity has risen. Thus in the light of above facts, the present study was undertaken to determine the toxicity of 2-naphthalene sulfonate in blood cells of Channa punctatus. For this, LD50 was determined and after selection of sublethal doses oxidative stress, genotoxicity and bioaccumulation were studied. For oxidative stress determination, biochemical markers such as malondialdehyde content and activities of superoxide dismutase, catalase, and glutathione-S-transferase were studied. Genotoxicity was studied using comet and micronucleus assay. Significant increase in oxidative stress and DNA damage in the exposed groups as compared to control group (P ≤ 0.05) was observed till 96 h. However, decreased values of all the studied parameters at 720 h (30 days) indicate repair capacity of fish. Further, the bio accumulative potential of 2-naphthalene sulfonate was assessed in blood plasma using high-performance liquid chromatography. The study revealed the toxic potential of 2-naphthalene sulfonate to aquatic organisms thus stressed on the need for the implementation of stringent policies regarding the management of such toxic compounds.

In recent years, increasing efforts have focused on production of organic-inorganic compound fertilizers using ammonium sulfite pulping waste liquor. However, their ecological effects on soil have not been studied. In this study, earthworm Eisenia fetida was exposed to various doses (0, 0.13, 0.26 and 0.52 kg/m2) for different time (7, 14, 21, and 28 d) to evaluate the effects of fertilizers made from pulping waste liquor, including reactive oxygen species (ROS) generation, antioxidant enzymes activities, glutathione S-transferase enzyme (GST) activity, malondialdehyde (MDA) content and DNA damage. Results showed that there were significant increase of ROS and MDA levels after 14 d, inducing production of antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT)) as well as GST. Before 14 d, excess ROS and MDA caused damage to the DNA of earthworms, leading to gradual increase of Olive tail moment (OTM) in the comet assay. With the exposure time extended to 28 d, owing to the combined effects of elimination of free radicals by antioxidant enzymes and detoxification enzymes as well as self-repairing function of cells, ROS and MDA levels declined slightly and OTM gradually decreased. In summary, this study indicated that there was a toxicological effect on earthworms when fertilizers made from pulping waste liquor were applied to soil, which needs more attention.

To study the extraction technology of polysaccharides (AAP) from Chinese herbal medicine formula and its mechanism of delaying aging. First, L9(3)4 orthogonal test was used to optimize the optimal enzyme-assisted extraction parameters of polysaccharides. And the anti-aging effects was evaluated by detecting mitochondrial function, protein, DNA, adhesion molecules and cell cycle in aging rats. The optimal extraction process parameters were the cellulase concentration of 1.5%, the pH at 5, the enzyme temperature at 50°C and the extraction time of 180 min. The anti-aging results showed that AAP can effectively increase the activities of malate dehydrogenase, succinate dehydrogenase and superoxide dismutase. It also can decrease the activity of monoamine oxidase and methane dicarboxylic aldehyde levels in the brain tissue. Meanwhile, the polysaccharides enhanced telomerase activity while reduced p16 protein expression of the brain mitochondria. In addition, the polysaccharides continued to improve heart damage and significantly lessen mitochondrial DNA concentrations. For a certain period of time, it also enhanced the activity of superoxide dismutase, reduced glutathione, glutathione peroxidase and decreased protein carbonyl and methane dicarboxylic aldehyde content of kidney in D-galactose-induced aging rats. Furthermore, the polysaccharides restored the number of cells in the peripheral blood lines and BMNC through inhibiting the drop of the number of red blood cells, white blood cells, platelets in the peripheral blood and bone marrow mononuclear cell of the aging rats. At the same time, AAP accelerated G1 phase cell to enter S phase in cell cycle in aging rats. Our research suggests that the polysaccharides may be a potential anti-aging agent and can be further developed as a functional food or new drug to delay aging or treat aging-related diseases.

Pulp and paper mill effluent can cause changes in the morphology and energy metabolism in the zebrafish (Danio rerio) testis. Betulin, a naturally occurring triterpene is commonly present in this type of effluent and is suspected of being involved in these effects. The aim of this study was to compare the effects pulp and paper mill effluent and betulin on various aspects of testicular physiology in the zebrafish. This included the in vitro effects of effluent and betulin on testicular lactate content and lactate dehydrogenase (LDH) activity. In addition, the effects of betulin on glucose uptake, glycogen, alanine aminotransferase (ALT), reactive oxygen and nitrogen species formation and oxidative damage in the testes were determined. Furthermore, we compared the effects and mechanism of action of betulin and effluent on calcium homeostasis in testes. In vitro exposure to both effluent and betulin decreased lactate and calcium influx, possibly due to the activation of the sodium‑calcium exchanger (NCX) pump. Additionally, betulin-treated testes had higher reactive oxygen species (ROS) and reduced glutathione (GSH) content, as well as increased glutathione transferase (GST) activity and a tendency towards decreased catalase (CAT) activity. Thus, this study shows that alterations in testis physiology caused by the pulp and paper mill effluent in the testis may be due in part to the actions of betulin.

We compared the effects of medium light roast (MLR) and medium roast (MR) paper-filtered coffee on antioxidant capacity and lipid peroxidation in healthy volunteers. In a randomized crossover study, 20 volunteers consumed 482 ± 61 ml/day of MLR or MR for four weeks. Plasma total antioxidant status (TAS), oxygen radical absorbance capacity (ORAC), oxidized LDL and 8-epi-prostaglandin F2α, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activity were measured at baseline and after the interventions. MLR had higher chlorogenic acids—(CGA; 334 mg/150 mL) and less caffeine (231 mg/150 ml) than MR had (210 and 244 mg/150 ml, respectively). MLR also had fewer Maillard reaction products (MRP) than MR had. Compared with baseline, subjects had an increase of 21 and 26 % in TAS, 13 and 13 % in CAT, 52 and 75 % in SOD, and 62 and 49 % in GPx after MLR and MR consumption (P < 0.001), respectively. ORAC increased after MLR (P = 0.004). No significant alteration in lipid peroxidation biomarkers was observed. Both coffees had antioxidant effects. Although MLR contained more CGA, there were similar antioxidant effects between the treatments. MRP may have contributed as an antioxidant. These effects may be important in protecting biological systems and reducing the risk of diseases related to oxidative stress.

Despite causing permanent hearing loss by damaging inner ear sensory cells, aminoglycosides (AGs) remain one of the most widely used classes of antibiotics in the world. Although the mechanisms of cochlear sensory cell damage are not fully known, reactive oxygen species (ROS) are clearly implicated. Mitochondrial-specific ROS formation was evaluated in acutely cultured murine cochlear explants exposed to gentamicin (GM), a representative ototoxic AG antibiotic. Superoxide (O2·−) and hydrogen peroxide (H2O2) were measured using MitoSOX Red and Dihydrorhodamine 123, respectively, in sensory and supporting cells. A 1-h GM exposure significantly increased O2·− formation in IHCs and increased H2O2 formation in all cell types. At the same time point, GM significantly increased manganese superoxide dismutase (MnSOD) levels while significantly decreasing copper/zinc superoxide dismutase (CuZnSOD) in cochlear sensory cells. This suggests (1) a rapid conversion of highly reactive O2·− to H2O2 during the acute stage of ototoxic antibiotic exposure and (2) that the endogenous antioxidant system is significantly altered by AGs. Fluorescence intensity-based measurements of reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] and mitochondrial membrane potential were measured to determine if increases in GM-induced ROS production were correlated with changes in mitochondrial metabolism. This project provides a basis for understanding the mechanisms of mitochondrial ROS production in cochlear cells exposed to ototoxic antibiotics. Understanding the nature of ototoxic antibiotic-induced changes in mitochondrial metabolism is critical for developing hearing loss treatment and prevention strategies.

Apoplastic fluid was extracted from maize (Zea mays L.) roots using two procedures: collection from the surface of intact plant roots by filter paper strips (AF) or vacuum infiltration and/or centrifugation from excised root segments (AWF). The content of cytoplasmic marker (glucose-6-phosphate, G-6-P) and antioxidative components (enzymes, organic acids, phenolics, sugars, ROS) were compared in the extracts. The results obtained demonstrate that AF was completely free of G-6-P, as opposed to AWF where the cytoplasmic constituent was detected even at mildest centrifugation (200 × g). Isoelectric focusing of POD and SOD shows the presence of cytoplasmic isoforms in AWF, and HPLC of sugars and phenolics a much more complex composition of AWF, due to cytoplasmic contamination. Organic acid composition differed in the two extracts, much higher concentrations of malic acid being registered in AF, while oxalic acid due to intracellular contamination being present only in AWF. EPR spectroscopy of DEPMPO spin trap in the extracts showed persistent generation of hydroxyl radical adduct in AF. The results obtained argue in favor of the filter strip method for the root apoplastic fluid extraction, avoiding the problems of cytoplasmic contamination and dilution and enabling concentration measurements in minute regions of the root.

Background: Excitotoxicity is one pathogenic mechanism proposed in amyotrophic lateral sclerosis (ALS), and loss of cortical inhibitory influence may be contributory. Patients with ALS who are homozygous for the D90A superoxide dismutase-1 (SOD1) gene mutation (homD90A) have a unique phenotype, associated with prolonged survival compared with patients with sporadic ALS (sALS). In this study, transcranial magnetic stimulation (TMS) was used to explore cortical excitation and inhibition. Flumazenil binds to the benzodiazepine subunit of the GABAA receptor, and 11C-flumazenil positron emission tomography (PET) was used as a marker of cortical neuronal loss and/or dysfunction, which might in turn reflect changes in cortical inhibitory GABAergic mechanisms. Methods: Cortical responses to single and paired stimulus TMS were compared in 28 patients with sALS and 11 homD90A patients versus 24 controls. TMS measures included resting motor threshold, central motor conduction time, silent period, intracortical inhibition (ICI), and facilitation. 11C-flumazenil PET of the brain was performed on 20 patients with sALS and nine with homD90A. Statistical parametric mapping was used to directly compare PET images from the two patient groups to identify those areas of relatively reduced cortical 11C-flumazenil binding that might explain differences in cortical excitability seen using TMS. Results: Increased cortical excitability, demonstrated by reduction in ICI, was seen in the patients with sALS but not the homD90A patients. A relative reduction in cortical 11C-flumazenil binding was found in the motor and motor association regions of the superior parietal cortices of the patients with sALS. Conclusions: A cortical inhibitory deficit in sALS was not demonstrable in a homogeneous genetic ALS population of similar disability, suggesting a distinct cortical vulnerability. 11C-flumazenil PET demonstrated that neuronal loss/dysfunction in motor and motor association areas may underlie this difference. The corollary, that there may be relative preservation of neuronal function in these areas in the homD90A group, has implications for understanding the slower progression of disease in these patients.

The study of the ageing of two paper types was performed on monitoring it during a simulated process by means of the measure of the photocatalytic degradation of the paper cellulose. Such evaluation was possible due to the combined responses of a photosensor based on titanium dioxide in suspension, of an enzymatic biosensor based on superoxide dismutase (SOD), of a specific conductivity sensor and of an enzymatic biosensor based on glucose oxidase.