Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 lg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-a) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-a, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

Aflatoxins (AF), a group of closely related, extremely toxic mycotoxins, produced by Aspergillus flavus and A. parasiticus can occur as natural contaminants of foods and feeds. Aflatoxins have been shown to be hepatotoxic, carcinogenic, mutagenic, and teratogenic to different animal species. Zizyphus spina-christi L. extract was investigated for its antifungal and antimicrobial activities. The aim of the present work was to evaluate the antioxidant activity of the methanol extract of Z. spina-christi L. leaves against the oxidative stress of aflatoxin in rats. Fourty male Sprague-Dawley male rats were divided into four groups including the control group, the group fed aflatoxin-contaminated diet (3 mg /kg diet) and the groups treated with Zizyphus extract (5 mg /kg b.w) alone or in combination with AF for 15 days. Biochemical analysis reveled that treatment with AF resulted in a significant increase in ALT, AST, cholesterol, triglycerides, uric acid, TNFa, LPO, NO and CEA, whereas it decrease significantly GPX and SOD. The histopatholgical examination of the liver, kidney and testis showed sever histological changes typical to those reported for aflatoxicosis. Animals treated with Zizyphus extract alone or plus AF showed a significant improvement in all biochemical parameters and histological picture of liver, kidney and testis. It could be concluded that Zizyphus extract have a power protective role against aflatoxicosis.

No abstract

Role of zinc oxide nanoparticles in alleviating hepatic fibrosis and nephrotoxicity induced by thioacetamide in rats. Journal: Canadian Journal of Physiology and PharmacologyManuscript ID cjpp-2017-0247.R1 AbstractThe present research studied the influence of zinc oxide nanoparticles (ZnO-NPs; 5mg, 7.5mg, 10 mg/Kg IP) on the liver and kidney injuries motivated by thioacetamide (TAA; 100mg/Kg IP).Each treatment was carried out three times weekly for eight weeks .ZnO-NPs relieved the decrease of hepatic or renal reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) induced by TAA. Moreover, ZnO-NPs lowered tissues malondialdehyde (MDA, an indicator for lipid peroxidation). TAA treatment led to a significant increase in plasma inflammatory markers (TNF-α, IL-6), liver enzymes (Gamma-glutamyltransferase (GGT), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and kidney function parameters (Creatinine, urea, uric acid). However, these parameters were reduced after treatment with ZnO-NPs. In addition, the hepatic fibrosis markers, Hydroxyproline level and α -smooth muscle actin immunopositive stain were lowered by ZnO-NPs. The protective effect of ZnO-NPs in respect to biochemical changes was also confirmed by histopatholgoical, and immunohistochemistry studies in the liver and kidney sections. Our results suggested that ZnONPs may attenuate TAA-toxicity via suppression of oxidative stress.Key words: zinc oxide nanoparticles, hepatic fibrosis, kidney injury, oxidative stress, inflammatory markers, histopathology, immunohistochemistry. Materials and methods ChemicalsThioacetamide (TAA) was purchased from Sigma (St. Louis, MO, USA). Other chemicals and reagents were of high analytical grade and were purchased from standard commercial suppliers. Zinc oxide nanoparticles were prepared by the sol gel method using 2 g of zinc acetate dehydrate as precursor dissolved in 14 ml of methanol, under magnetic stirring for 2 h. Then, the resulting solution undergos rapid drying to obtain a white powder. The obtained powder was calcined at 500 °C for 2 h to obtained ZnO nanoparticles. The crystalline phases of the obtained nanopowder were identified by X-ray diffraction (XRD) using a Bruker D5005 powder X-ray diffractometer.Crystallite size was estimated from the Debye-Sherrer Equation and found to be 38-54 nm.Furthermore, the obtained nanopowder was characterized in terms of morphology, structure, and optics characteristics using a number of analytical techniques reported by Omri et al 2016. Preparation of zinc oxide nanoparticles suspensionThe nanoparticles of zinc oxide were suspended in 1% sodium carboxy methyl cellulose as stabilizer or surfactant, stirred with a magnetic stirrer for 5 minutes and then dispersed by ultrasonic vibration for 15 min (Wang et al. 2008). In order to avoid the aggregation of the particles, fresh suspension was prepared before every use. Animals and experimental groupsForty male albino (Sprague-Dawley) rats weighing 150 ± 10 g. were used in the study. Each 4 rats s...

Melatonin (ML) is a potent antioxidant that reduces oxidative stress. This study was designed to examine the protective effect of melatonin on potassium dichromate- (PDC-) induced male reproductive toxicity. Forty rats were divided into five groups: the control group, rats administered PDC orally (10 mg/kg body weight) for eight weeks, rats administered ML intraperitoneally at doses of either 2.5 or 5 mg/kg followed by the administration of PDC, and rats administered 5 mg/kg ML only. The treatment of rats with PDC led to a decrease in the levels of plasma sex hormones, glutathione, superoxide dismutase, catalase, carnitine, sperm count, and motility. Testicular malondialdehyde levels, nitric oxide concentrations, and abnormalities increased significantly in the PDC group. Melatonin administration to the PDC-treated rats reduced the increase of malondialdehyde and restored the activity of antioxidant enzymes (superoxide dismutase and catalase), glutathione, and sex hormone levels. Moreover, ML attenuated PDC-induced increase in levels of tumor necrosis factor-alpha or interleukin-6. ML alleviated histopathological changes and an increase of p53-positive immune reaction due to PDC. Furthermore, ML inhibited PDC-induced decrease in the DNA content of spermatogenic cells. This study proposed that melatonin may be useful in mitigating oxidative stress-induced testicular damage due to potassium dichromate toxicity.

No abstract

No abstract

This study investigated the effect of the serotonin selective reuptake inhibitors (SSRIs) fluoxetine, sertraline, fluvoxamine and the tricyclic antidepressant (TCA) impiramine on oxidative stress in brain and liver induced by lipopolysaccharide administration in mice. Each drug was administered subcutaneously at doses of 10 or 20 mg/kg, for two days prior to intraperitoneal (i.p.) administration of lipopolysaccharide E (LPS: 200 µg/kg). Mice were euthanized 4 h after administration of the lipopolysaccharide. Lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) concentrations were measured in brain and liver. Results: The administration of lipopolysaccharide increased oxidative stress in brain and liver; it increased brain MDA by 36.1 and liver MDA by 159.8 %. GSH decreased by 34.1 % and 64.8 % and nitric oxide increased by 78.7 % and 103.8 % in brain and liver, respectively. In brain, MDA decreased after the administration of sertraline and by the lower dose of fluoxetine or fluvoxamine, but increased after the higher dose of imipramine. Reduced glutathione increased after sertraline, fluvoxamine and the lower dose of fluoxetine or imipramine. Nitric oxide decreased by sertraline, fluoxetine, fluvoxamine and by the lower dose of imipramine. In the liver, all drugs decreased MDA and increased GSH level. Nitric oxide is decreased by sertraline, fluvoxamine and by the lower dose of fluoxetine or imipramine. It is concluded that, during mild systemic inflammatory illness induced by peripheral bacterial endotoxin injection, the SSRIs fluoxetine, sertraline and fluvoxamine reduced, while the TCA impiramine increased oxidative stress induced in the brain. The SSRIs as well as imipramine reduced oxidative stress due to lipopolysaccharide in liver tissue.