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The concept of chelation therapy as a valuable therapeutic approach in neurological disorders led us to develop multi-target, non-toxic, lipophilic, brain-permeable compounds with iron chelation and anti-apoptotic properties for neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), age-related dementia and amyotrophic lateral sclerosis (ALS). Herein, we reviewed our two most effective such compounds, M30 and HLA20, based on a multimodal drug design paradigm. The compounds have been tested for their mechanisms of action using animal and cellular models such as APP/PS1 AD transgenic (Tg) mice, G93A-SOD1 mutant ALS Tg mice, C57BL/6 mice, Neuroblastoma × Spinal Cord-34 (NSC-34) hybrid cells, a battery of behavior tests, and various immunohistochemical and biochemical techniques. These novel iron chelators exhibit neuroprotective activities by attenuating relevant neurodegenerative pathology, promoting positive behavior changes, and up-regulating neuroprotective signaling pathways. Taken together, these results suggest that our multifunctional iron-chelating compounds can upregulate several neuroprotective-adaptive mechanisms and pro-survival signaling pathways in the brain and might function as ideal drugs for neurodegenerative disorders, such as PD, AD, ALS, and aging-related cognitive decline, in which oxidative stress and iron-mediated toxicity and dysregulation of iron homeostasis have been implicated. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 induces a broad range of clinical manifestations. Besides the main receptor, ACE2, other putative receptors and co-receptors have been described and could become genuinely relevant to explain the different tropism manifested by new variants. In this study, we propose a biochemical model envisaging the competition for cysteine as a key mechanism promoting the infection and the selection of host receptors. The SARS-CoV-2 infection produces ROS and triggers a massive biosynthesis of proteins rich in cysteine; if this amino acid becomes limiting, glutathione levels are depleted and cannot control oxidative stress. Hence, infection succeeds. A receptor should be recognized as a marker of suitable intracellular conditions, namely the full availability of amino acids except for low cysteine. First, we carried out a comparative investigation of SARS-CoV-2 proteins and human ACE2. Then, using hierarchical cluster protein analysis, we searched for similarities between all human proteins and spike produced by the latest variant, Omicron BA.1. We found 32 human proteins very close to spike in terms of amino acid content. Most of these potential SARS-CoV-2 receptors have less cysteine than spike. We suggest that these proteins could signal an intracellular shortage of cysteine, predicting a burst of oxidative stress when used as viral entry mediators. [ABSTRACT FROM AUTHOR]

The underlying pathophysiological mechanisms of hepatic ischemia-reperfusion (I/R) injury have not been completely elucidated. However, it is well known that oxidative stress, caused by a burst of reactive oxygen species (ROS) production during the reperfusion phase, plays a crucial role. A growing body of evidence indicates that the intracellular availability of free iron represents a requirement for ROS-induced adverse effects, as iron catalyzes the generation of highly reactive free radicals. The aim of this study was to examine whether a combination of iron chelators with varying lipophilicity could offer enhanced protection against I/R by diminishing the conversion of weak oxidants, like H 2 O 2 , to extremely reactive ones such as hydroxyl radicals (HO. ). HepG2 cells (hepatocellular carcinoma cell line) were exposed to oxidative stress conditions after pre-treatment with the iron chelators desferrioxamine (DFO) and deferiprone (DFP) alone or in combination. Labile iron pool was estimated using the calcein-acetoxymethyl ester (calcein-AM) method and DNA damage with the comet assay. We subsequently used a rabbit model (male New Zealand white rabbits) of hepatic I/R-induced injury to investigate, by measuring biochemical (ALT, ALT, ALP, γGT) and histological parameters, whether this may be true for in vivo conditions. The combination of a membrane-permeable iron chelator (DFP) with a strong membrane-impermeable one (DFO) raises the level of protection in both hepatic cell lines exposed to oxidative stress conditions and hepatic I/R rabbit model. Our results show that combinations of iron chelators with selected lipophilicity and iron-binding properties may represent a valuable strategy to protect against tissue damage during reperfusion after a period of ischemia. [Display omitted] • Excess production of reactive oxygen species triggers reperfusion injury. • Intracellular free iron catalyzes the generation of highly reactive free radicals. • Chelation of intracellular iron protects hepatic cell lines against oxidative stress. • Iron chelating drugs attenuates liver ischemia/reperfusion injury in rabbits. • Optimum protection is offered by combining membrane-permeable and impermeable drugs. [ABSTRACT FROM AUTHOR]

Introduction: Nonalcoholic fatty liver disease [NAFLD] is considered the commonest form of liver disorders around the globe. Curcumin is known to have protective anti-oxidative characteristics. Objective: The present work aims to investigate the effect of curcumin on NAFLD. Materials and Methods: 60 Wistar male rats divided into four groups: Group I: Control group received rat chew diet for 12 weeks. Group II: Fatty liver group, animals received high-fat diet for 12 weeks. Group III: Fatty liver group injected intraperitoneally [IP] with 1 ml/kg body weight dimethyl sulfoxide [DMSO] every other day for 8 weeks. Group IV: Fatty liver group injected with 50 mg/kg body weight, curcumin dissolved in DMSO, IP every other day for 8 weeks Animals were sacrificed at the end of the experiment. Blood was collected for separation of sera and liver tissues to prepare liver homogenates. Results: Fasting blood sugar, insulin,and homeostatic model for insulin resistance [HOMA-IR] were significantly higher in rats of NAFL group than control group ( p<0.05, p<0.001, p<0.001 respectively) while insulin and HOMA-IR were lower in curcumin treated group (group IV) when compared to DMSO group (group III) (p<0.05, p<0.001respectively). Cholesterol concentrations in liver homogenate were siginificantly decreased in curcumin group when compared to DMSO and NAFL group (p<0.05).Serum TG of NAFL group was significantly higher than DMSO and curcumin groups ( p<0.05).Triglycerides in liver homogenate of curcumin group was lower than that of NAFL and DMSO groups (p<0.001,p<0.05 respectively). Serum LDL-cholesterol was significantly higher in NAFL group when compared to control one (p<0.05) but decreased in curcumin group when compared to NAFLand DMSO groups (p<0.001). Serum VLDL in NAFL group was significantly higher than that of DMSO and curcumin groups(p<0.05). MDA concentration was higher in NAFL group compared to control group (p<0.001) and was significantly decreased in curcumin group compared to DMSO and NAFL groups (p<0.001). Total glutathione levels in liver homogenate was significantly decreased in NAFL group compared to control group and increased in curcumin group compared to NAFL and DMSO groups (p<0.001). Triglycerides in liver homogenate had a positive correlation with HOMA-IR (r=0.724, p<0.05) and malondialdhyde [MDA] in curcumin group (r=0.807, p<0.001) There was a positive correlation between insulin level and serum VLDL (r=0.547, p<0.05) in curcumin group. Conclusions: Enhanced oxidative stress and reduced antioxidant status of the plasma and liver are greatly involved in the induction and progression of NAFL. Curcumin has antioxidant defense mechanism, improves serum lipid profile, decreases steatosis in the liver and improves insulin sensitivity in nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Diabetes and cancer have common physiological and biochemical mechanisms. Metformin is the preferred drug of choice for the treatment of diabetes. Prostate cancer can be modeled in by injection of MAT-Lylu cells. A model of diabetes in rats is induced by streptozotocin injectıon. In the current study, we explored the mechanisms by which diabetes accelerates cancer, and evaluated the effects of metformin to know whether it has any impact against the damage caused by cancer and diabetic + cancer via histopathological and biochemical parameters of kidney tissue. The experiment was carried out in rats. Groups 1-Control, 2- Diabetic, 3-Cancer, 4-Diabetic + cancer, 5-Diabetic + cancer + metformin, 6-Cancer + metformin. Metformin treatment was applied by gavage every day. The research ended on the 14th day. The collected kidney tissue sections were stained with Hematoxylin-Eosin. Histological evaluation showed moderate to severe damage to the kidney tissue following diabetic and cancer processess. In diabetic, cancer and diabetic + cancer groups, reduced glutathione levels, total antioxidant status, sodium/potassium-ATPase and paraoxonase1 activities were found to be significantly abated. While advanced oxidized protein products, lipid peroxidation, nitric oxide, tumor necrosis factor-alpha, reactive oxygen species levels, total oxidant status, catalase, superoxide dismutase, glutathione-related antioxidant enzymes, myeloperoxidase, and arginase activities were significantly raised. The administration of metformin reversed these defects. The outcome of the reveals that histopathological and biochemical damage in cancer and diabetes + cancer groups decreased in the groups that received metformin. In conclusion, metformin treatment can be considered an adjuvant candidate for kidney tissue in diabetes, prostate cancer and cancer therapy related damage. [ABSTRACT FROM AUTHOR]

Cantharidin (CTD) is a promising anticancer drug; however, its dosage is limited by hepatotoxicity. We previously showed that Astragalus polysaccharides (APS) effectively improved chemical liver injury. In this study, we established a CTD‐induced subacute liver injury mouse model and examined the effects of APS on weight, liver indexes, histopathology, serum biochemical indexes and liver metabolism. Compared with the control group, mice in the CTD model group had obvious liver damage, which was partially prevented by APS. Metabolomics demonstrated that CTD caused liver damage mainly by regulating glycerophospholipid metabolism, ABC transporter pathways and choline metabolism in cancer in vivo. APS regulated primary bile acid biosynthesis and glycerophospholipid metabolism, thus decreasing the liver damage caused by CTD. This study revealed the protective mechanism of APS against CTD‐induced liver injury from the perspective of metabolomics. The results provide an important basis for analysing the mechanism of CTD‐induced liver toxicity and for assessing clinical treatment options to reduce CTD liver toxicity. [ABSTRACT FROM AUTHOR]

Tauopathies belong to a heterogeneous class of neuronal diseases resulting in the metabolic disturbance. A disulfide natural compound of Alpha-Lipoic acid (ALA) has shown numerous pharmacologic, antioxidant, and neuroprotective activities under neuropathological conditions. The aim of this study was to investigate the neuroprotective effects of ALA on the tauopathy-induced oxidative disturbance and behavioral deficits. The transgenic Drosophila model of tauopathy induced by human tauR406W using GAL4/UAS system and effects of ALA (0.001, 0.005, and 0.025 % w/w of diet) on the neuropathology of tau in younger (20 days) and older (30 days) adults were investigated via biochemical, molecular, behavioral and in-situ tissue analyses. Expression of apoptosis-related proteins involving Drosophila Cyt-c-d (trigger of intrinsic apoptosis) and DrICE (effector caspase) were upregulated in both ages (20 and 30 days) and DIAP1 (caspase inhibitor) has reduced only in older model flies compared to the controls. Remarkably, all doses of ALA increased DIAP1 and glutathione (GSH) as well as reducing Cyt-c-d and lipid peroxidation (LPO) in the younger flies compared to the model flies. Moreover, the higher doses of ALA were able to decrease thiol concentrations, to increase total antioxidant capacity, and to improve the behavioral deficits (locomotor function, olfactory memory, and ethanol sensitivity) in the younger flies. On the other hand, only a higher dose of ALA was able to decrease DrICE, Cyt-c-d, LPO, and thiol as well as increasing antioxidant capacity and decreasing ethanol sensitivity (ST50, RT50) in the older flies. TUNEL assay showed that all doses of ALA could potentially increase the DIAP1/DrICE ratio and exert anti-apoptotic effects on younger, but not on the older adults. Furthermore, data obtained from the in-situ ROS assay confirmed that only a higher dose of ALA significantly decreased the ROS level at both ages. Our data showed that an effective neuroprotective dose of ALA and its mechanism of action on this model of tauopathy could potentially be influenced by longevity. Moreover, it was shown that ALA prevents apoptosis and decreases the redox homeostasis, and this partially explains the mechanism by which ALA diminishes behavioral deficits. [ABSTRACT FROM AUTHOR]

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received "conventional" SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the future. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CPF) is a widely used insecticide that causes toxicity to living organisms through the production of free radicals. Cerium oxide nanoparticles (CeO 2 NPs) are a new antioxidant agent that has proved therapeutic effects. We evaluated the effect of CeO 2 NPs on CPF hepatotoxicity. Forty rats were randomized into four groups. Group I: rats received 1 ml corn oil by gastric tube once daily and 0.5 ml PBS by intra-peritoneal injection twice a week for 4 weeks. Group II: received CeO 2 NPs 0.5 mg/kg in PBS by i.p. injection, twice weekly for four weeks. Group III: were treated with oral administration of CPF 13.5 mg/kg in corn oil daily for 4 weeks. Group IV: received CPF as in group III, then each animal received CeO 2 NPs twice weekly for four weeks as in group II. Twenty-four hours after the last dose, rats were anesthetized and sera were collected for liver enzymes assessment. Afterwards, rats were sacrificed, livers were excised, the right lobe of each liver was fixed for immunohistochemical studies, and the left lobe was homogenized for oxidative profile assessment and molecular analysis. CPF group showed significant increase in liver transaminases, disturbance of the oxidative profile with up-regulation of BAX expression and down-regulation in the Bcl-2, Gadd45 and NFE2L2. CPF caused severe histopathological liver damage as well as significant increase in anti-Caspase 3 and TNF immunostaining. The CeO 2 NPs treated group revealed significant improvement of all previous parameters. CeO 2 NPs could alleviate CPF hepatoxicity through decreasing expression of the inflammatory and apoptotic proteins and increasing the activity of antioxidant enzymes. [Display omitted] • Chronic exposure to Chlorpyrifos (CPF) induced hepatotoxicity in rats. • CPF induced up-regulation of inflammatory markers and apoptotic markers. • Cerium oxide nanoparticles (CeO 2 NPs) could alleviate CPF- induced hepatoxicity. • CeO 2 NPs cause down-regulation of anti-oxidative (SOD, CAT and NFE2L2) markers. • CeO 2 NPs cause down-regulation of anti-apoptotic (Bcl 2 & Gadd45) markers. [ABSTRACT FROM AUTHOR]

A soil microcosm study was performed to examine the impacts of cerium oxide nanoparticles ( nCeO) on the physiology, productivity, and macromolecular composition of barley ( Hordeum vulgare L.). The plants were cultivated in soil treated with nCeO at 0, 125, 250, and 500 mg kg (control, nCeO-L, nCeO-M, and nCeO-H, respectively). Accumulation of Ce in leaves/grains and its effects on plant stress and nutrient loading were analyzed. The data revealed that nCeO-H promoted plant development resulting in 331 % increase in shoot biomass compared with the control. nCeO treatment modified the stress levels in leaves without apparent signs of toxicity. However, plants exposed to nCeO-H treatment did not form grains. Compared with control, nCeO-M enhanced grain Ce accumulation by as much as 294 % which was accompanied by remarkable increases in P, K, Ca, Mg, S, Fe, Zn, Cu, and Al. Likewise, nCeO-M enhanced the methionine, aspartic acid, threonine, tyrosine, arginine, and linolenic acid contents in the grains by up to 617, 31, 58, 141, 378, and 2.47 % respectively, compared with the rest of the treatments. The findings illustrate the beneficial and harmful effects of nanoceria in barley. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: In this study, 5-Flurouracil (5-FU) induced toxic effects were evaluated after treating with morin with respect to biochemical and morphological evaluation of erythrocyte with reference to clinical blood parameters, membrane associated damages, lipid peroxidation, ATPases and antioxidant enzymes in in vitro erythrocyte after scheduled treatment with 5-FU. 5-FU was prepared using saline followed by administration in rats to evaluate its toxic effects. Protective effect of morin was assessed by estimating antioxidant marker enzymes, lipid peroxidation, membrane bound enzymes and morphological changes, clinical hematological parameters by automated and manual standard protocols. 5-FU administration moderately increased the percentage of hemolysis, carboxyhemoglobin, hemin, lipid peroxidation and osmotic fragility in rat erythrocytes whereas morin treatment significantly altered to near normalcy. The levels of protein carbonyls significantly increased whereas the level of protein thiol decreased significantly in erythrocytes treated with 5-FU and reverted back to near normal upon morin treatment. The level of antioxidant enzyme and membrane bound ATPases were decreased significantly in 5-FU treated erythrocytes and brought back to the normal levels. The present study signifies that morin treatment can reduce the abnormalities posed by 5-FU by ameliorating oxidative stress. These clinical and biochemical observations shed the possibility that morin may render protection against 5-FU treated toxicity. [Copyright &y& Elsevier]

The present study was aimed to evaluate the protective effect of hesperidin against immobilization-stress-induced alterations in biochemical, behavioral, and mitochondrial functions inmice. In many instances neuroscientists have reported that acute immobilization stress for 6 h resulted in anxiety and impaired locomotor activity due to excess oxidative-nitrergic stress, depletion of antioxidant defense mechanisms, and mitochondrial dysfunction in animals. In the present study, 6 h of acute immobilization stress had significantly altered the behavioral (anxiety and memory) and biochemical parameters coupled with mitochondrial dysfunction in Swiss albino mice. Fourteen days of pretreatment with Hesperidin (50 and 100 mg/kg, p.o.) significantly and dosedependently inhibited the behavioral and biochemical alterations and mitochondrial dysfunction caused by acute immobilization stress. Furthermore, pre-treatment of l-arginine (50mg/kg, i.p.), a nitric oxide precursor, reversed the protective effect of Hesperidin (50 and 100 mg/kg) (P < 0.05). In contrast, pretreatment of l-NAME (5mg/kg, i.p.), a nitric oxide synthase inhibitor, potentiated the protective effect of Hesperidin (P < 0.05). These results suggest the possible involvement of nitrergic pathway in the protective effect Hesperidin against immobilization-stress-induced behavioral, biochemical, and mitochondrial dysfunction in mice. [ABSTRACT FROM AUTHOR]

(1) Background: Size at birth is an important early determinant of health later in life. The prevalence of small for gestational age (SGA) newborns is high worldwide and may be associated with maternal nutritional and metabolic factors. Thus, estimation of fetal growth is warranted. (2) Methods: In this work, we developed an artificial neural network (ANN) model based on first-trimester maternal body fat composition, biochemical and oxidative stress biomarkers, and gestational weight gain (GWG) to predict an SGA newborn in pregnancies with or without obesity. A sensibility analysis to classify maternal features was conducted, and a simulator based on the ANN algorithm was constructed to predict the SGA outcome. Several predictions were performed by varying the most critical maternal features attained by the model to obtain different scenarios leading to SGA. (3) Results: The ANN model showed good performance between the actual and simulated data (R2 = 0.938) and an AUROC of 0.8 on an independent dataset. The top-five maternal predictors in the first trimester were protein and lipid oxidation biomarkers (carbonylated proteins and malondialdehyde), GWG, vitamin D, and total antioxidant capacity. Finally, excessive GWG and redox imbalance predicted SGA newborns in the implemented simulator. Significantly, vitamin D deficiency also predicted simulated SGA independently of GWG or redox status. (4) Conclusions: The study provided a computational model for the early prediction of SGA, in addition to a promising simulator that facilitates hypothesis-driven constructions, to be further validated as an application. [ABSTRACT FROM AUTHOR]

Takotsubo syndrome (TTS) presents as an acute coronary syndrome characterized by severe left ventricular (LV) dysfunction and non-obstructive coronary artery disease that typically shows spontaneous recovery within days or weeks. The mechanisms behind TTS are mainly related to beta-adrenergic overstimulation and acute endogenous catecholamine surge, both of which could increase oxidative status that may induce further deterioration of cardiac function. Although several studies reported evidence of inflammation and oxidative stress overload in myocardial tissue of TTS models, systemic biochemical evidence of augmented oxidant activity in patients with TTS is lacking. In this study, serum samples of ten TTS patients and ten controls have been analyzed using 1H-NMR spectroscopy. The results of this pilot study show a marked alteration in the systemic metabolic profile of TTS patients, mainly characterized by significant elevation of ketone bodies, 2-hydroxybutyrate, acetyl-L-carnitine, and glutamate levels, in contrast with a decrease of several amino acid levels. The overall metabolic fingerprint reflects a systemic response to oxidative stress caused by the stressor that triggered the syndrome's onset. [ABSTRACT FROM AUTHOR]

• Vegetation spectroscopy was used to evaluate pomegranate/ozone interaction. • Spectral signatures accurately discriminated cultivars and ozone treatments. • Spectral models accurately estimated leaf traits related to oxidative stress. • Leaf traits derived from spectra showed a lower O 3 -tolerance of Wonderful cultivar. Techniques to monitor oxidative stress pre-visually are essential to optimize plant management. Here, we investigated the capability of hyperspectral reflectance (350−2500 nm) to characterize responses of two pomegranate cultivars (Parfianka and Wonderful) under ozone (O 3) episodes at a gradient of concentrations (50, 100 and 200 ppb for 5 h). Analyzing spectral signatures collected rapidly and non-destructively from asymptomatic leaves, we accurately discriminated the two cultivars, as well as controls from plants exposed to O 3 , in particular those under the higher oxidative stress (i.e. 200 ppb). These discriminations were especially accurate in Wonderful at the end of the exposure (5 h from the beginning of exposure; FBE), and at 24 h FBE. Furthermore, using a partial least squares regression (PLSR) approach, we constructed predictive spectral models to estimate from spectra an array of commonly used physiological and biochemical leaf traits related to plant/oxidative stress interaction (photosynthesis, lipid peroxidation, enzymatic and non-enzymatic antioxidants). Most traits were relatively well predicted by spectroscopic models (model goodness-of fit for validation, R2 : 0.77−0.50). Finally, variations of spectra-derived vegetation indices and leaf traits derived from spectra confirmed the lower O 3 -tolerance of the Wonderful cultivar, when exposed to 200 ppb. Overall, the present study shows that the proposed spectroscopic approach can rapidly and non-destructively assess early oxidative stress conditions in plants, and consequently it can help in increasing plant yield and quality. Limitations of the approach are also presented and discussed. [ABSTRACT FROM AUTHOR]

Increased levels of the superoxide radical are associated with oxidative damage to healthy tissues and with elimination of malignant cells in a living body. It is desirable that a chemotherapeutic combines pro-oxidant behavior around and inside tumors with antioxidant action near healthy cells. A complex consisting of a pro-oxidant cation and antioxidant ligands could be a potential anticancer agent. Ga(III) salts are known anticancer substances, and 5-aminoorotic acid (HAOA) is a ligand with antioxidant properties. The in vitro effects of HAOA and its complex with Ga(III) (gallium(III) 5-aminoorotate (GaAOA)) on the in vitro accumulation of superoxide and other free radicals were estimated. Model systems such as potassium superoxide (KO2), xanthine/xanthine oxidase (X/XO), and rat blood serum were utilized. Data suggested better antioxidant effect of GaAOA compared to HAOA. Evidently, all three ligands of GaAOA participated in the scavenging of superoxide. The effects in rat blood serum were more nuanced, considering the chemical and biochemical complexity of this model system. It was observed that the free-radical-scavenging action of both compounds investigated may be manifested via both hydrogen donation and electron transfer pathways. It was proposed that the radical-scavenging activities (RSAs) of HAOA and its complex with Ga(III) may be due to a complex process, depending on the concentration, and on the environment, nature, and size of the free radical. The electron transfer pathway was considered as more probable in comparison to hydrogen donation in the scavenging of superoxide by 5-aminoorotic acid and its gallium(III) complex. [ABSTRACT FROM AUTHOR]

Accumulation of methylglyoxal (MG) arising from downregulation of its primary degrading enzyme glyoxalase-1 (Glo1) is an underlying cause of diabetic cardiomyopathy (DC). This study investigated if expressing Glo1 in rat hearts shortly after the onset of Type 1 diabetes mellitus (T1DM) would blunt the development of DC employing the streptozotocin-induced T1DM rat model, an adeno-associated virus containing Glo1 driven by the endothelin-1 promoter (AAV2/9-Endo-Glo1), echocardiography, video edge, confocal imaging, and biochemical/histopathological assays. After eight weeks of T1DM, rats developed DC characterized by a decreased E:A ratio, fractional shortening, and ejection fraction, and increased isovolumetric relaxation time, E: e' ratio, and circumferential and longitudinal strains. Evoked Ca2+ transients and contractile kinetics were also impaired in ventricular myocytes. Hearts from eight weeks T1DM rats had lower Glo1 and GSH levels, elevated carbonyl/oxidative stress, microvascular leakage, inflammation, and fibrosis. A single injection of AAV2/9 Endo-Glo1 (1.7 × 1012 viron particles/kg) one week after onset of T1DM, potentiated GSH, and blunted MG accumulation, carbonyl/oxidative stress, microvascular leakage, inflammation, fibrosis, and impairments in cardiac and myocyte functions that develop after eight weeks of T1DM. These new data indicate that preventing Glo1 downregulation by administering AAV2/9-Endo-Glo1 to rats one week after the onset of T1DM, blunted the DC that develops after eight weeks of diabetes by attenuating carbonyl/oxidative stresses, microvascular leakage, inflammation, and fibrosis. [ABSTRACT FROM AUTHOR]

• Nandrolone abuse had deleterious effects. • ND impaired renal and hepatic functions. • ND deteriorated hormonal activities. • ND disturbed oxidant/antioxidant balance. Nandrolone decanoate (ND) is one of the most commonly abused anabolic androgenic steroids compounds in the world owing to its ability to improve physical performance but its abuse is associated with several adverse effects. The current study was performed to evaluate the effect of recommended and overdose of nandrolone decanoate (ND) for short and long term on the alterations of biochemical markers related to kidney, liver, adrenal, thyroid gland functions and oxidant and antioxidant activities. Sixty male rats were randomly assigned into two major groups. The first was treated with ND for 6 weeks and the second was treated with same drug for 12 weeks. Each of these groups was further subdivided into three sub groups: 1-Control (untreated rats), 2- Rats intraperitoneally injected with ND 3 mg/kg weekly, 3- Rats intraperitoneally injected with ND 15 mg/kg weekly. Administration of high ND dose for either short or long term significantly elevated kidney function biomarkers, liver enzymes both in serum, cytosol and mitochondria, insignificantly increased thyroid function, significantly increased adrenal function while, decreased ACTH. Moreover, oxidative stress biomarkers were significantly upregulated associated with depression in antioxidants activities. Administration of high ND dose for either short or long term as well as the repeated use of recommended ND dose for long term proved to have harmful effects manifested in impairing the functions of kidneys, liver, thyroid and adrenal glands as well as oxidant antioxidant balance. [ABSTRACT FROM AUTHOR]