chrysin and sodium-arsenite

We aimed to study the beneficial property of chrysin (CHR) by targeting its antioxidant and anti-inflammatory effects on nephrotoxicity induced by sodium arsenite (SA).. We have used the 35 male Wistar rats in five equal groups (n = 7). Normal saline in (5 ml/kg; p.o.; 21 days) was given to the control group. Sodium arsenite (10 mg/kg; p.o.; 14 days) was given to the SA group. CHR (25, 50 and 100 mg/kg; p.o.; 21 days) and SA (10 mg/kg; p.o.; 14 days from the 7th day of the experiment) was given to the SA + CHR 25, 50 and 100 groups. On the 22nd day of the experiment, the animals' bloods and kidneys were taken, and then we have performed functional, biochemical and histological assessment.. CHR pre- and alongside administration (more potently at dose of 100 mg/kg) with SA reduced the SA-induced alterations in serum creatinine and blood urine nitrogen levels. Increased levels of protein carbonyl, myeloperoxidase, malondialdehyde and nitric oxide in kidney tissue were decreased by CHR treatment. CHR administration increased the levels of glutathione and activities of glutathione peroxidase, catalase and superoxide dismutase in renal tissue. Moreover, treatment with CHR reduced the levels of inflammatory mediators including interleukin 1 beta and tumor necrosis factor alpha in renal tissue. The renal histological lesions induced SA were mitigated by CHR treatment in dose dependent manner.. The results of present study suggested that administration of CHR before and alongside with SA attenuated the renal toxic effects of SA via antioxidative stress and anti-inflammatory effects.

Topics: Animals; Antioxidants; Arsenites; Catalase; Flavonoids; Glutathione; Glutathione Peroxidase; Inflammation; Interleukin-1beta; Kidney; Male; Malondialdehyde; Nitric Oxide; Oxidative Stress; Peroxidase; Protein Carbonylation; Rats, Wistar; Sodium Compounds; Tumor Necrosis Factor-alpha

Arsenic as a one of the most important toxic metals could induce hepatotoxicity. Previous reports revealed the significance of oxidative stress in promoting of arsenic-induced liver toxicity. The aim of the present investigation is to evaluate the effect of chrysin (CHR), a natural flavonoid with potent antioxidant activity, against sodium arsenite (SA)-induced hepatotoxicity. Thirty male Wistar rats were divided into four groups: Group 1: received normal saline (2 ml/kg/day, orally for 21 days), Group 2: received SA (10 mg/kg/day, orally for 14 days), Group 3, 4 and 5: received CHR (25, 50 and 100 mg/kg/day, respectively, orally for 21 days) and SA (10 mg/kg/day, orally for 14 days) from the 7th day. Serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were evaluated. Moreover, liver glutathione peroxidase and myeloperoxidase activity as well as levels of protein carbonylation, malondialdehyde, glutathione, catalase, nitric oxide, superoxide dismutase, tumor necrosis factor-α and interleukin-1β were evaluated. Moreover, histological evaluation was done. Our results revealed that treatment with CHR (more potentially at the dose of 100 mg/kg/day) before and alongside with SA significantly mitigated the SA-induced hepatotoxicity. Also, the hepatoprotective effect of CHR was verified by the histological evaluation of the liver. The results of current study demonstrated that CHR (100 mg/kg/day) could mitigate the oxidative stress and inflammation induced by SA in liver tissue.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Antioxidants; Arsenites; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Flavonoids; Glutathione; Glutathione Peroxidase; Liver; Male; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Wistar; Sodium Compounds; Superoxide Dismutase

Chrysin (CHR) is a food-based bioactive ingredient whereas, sodium arsenite (SA) is one of the major contaminant in drinking water. When ingested, SA contributes to tissue damage due to bioactivation by S-adenosyl methionine (SAM)-dependent methyltransferase. Hence, the needs to nullify this effect by investigating the potentials of CHR on SA-induced genotoxicity in rats. The experiment was divided into two successive stages (ameliorative and preventive, curative studies) for 1 week. Rats were divided into four groups: distilled water, 10mg/kg SA, 10mg/kg CHR and co-administration. In stage 2, the experimental groups were given either CHR or SA for 1 week, and treated in reversed order for additional week. Lipid peroxidation, protein carbonyl and DNA fragmentation in liver, blood brain and bone marrow cells micronucleus were assayed for using standard protocols. Molecular docking of SAM-dependent methyltransferase in the presence of CHR was conducted. CHR significantly ( p < 0.05) decreased the level of lipid peroxidation, protein carbonyls and DNA fragmentation in blood, liver and brain tissues as against group treated with SA. It also significantly ( p<0.05) reduced the level of micronuclei generated in bone marrow cells. The effects of CHR were shown to be ameliorative, preventive and curative in nature. Furthermore, CHR was able to dock (with binding energy of -24.81 kcal/mol and predicted inhibition kinetic constant (Ki) of 0.959 µM) into the active site of SAM-dependent methyltransferase with strong hydrogen bond and hydrophobic interactions. The study might have unravelled the potentials of CHR against SA-induced chromosomal and DNA damage, which might be due to inhibition of SAM-dependent methyltransferase.

Topics: Animals; Arsenites; Chromosome Aberrations; Computer Simulation; DNA Fragmentation; DNA Repair; Flavonoids; Hydrophobic and Hydrophilic Interactions; Lipid Peroxidation; Male; Methyltransferases; Micronucleus Tests; Molecular Docking Simulation; Mutagens; Protein Carbonylation; Rats; Rats, Wistar; S-Adenosylmethionine; Sodium Compounds; Thermodynamics