Evaluating the protective effect of metformin against diclofenac-induced oxidative stress and hepatic damage: In vitro and in vivo studies.

Diclofenac (DIC) is one of the most commonly prescribed non-steroidal anti-inflammatory drugs and has been shown to cause oxidative stress and liver injury. The current study investigated protective effects of metformin against DIC-induced hepatic toxicity in both in vitro and in vivo models. For the in vitro study, HepG2 cells were exposed to DIC in the presence or absence of metformin. The effect of metformin on cell viability was evaluated by MTT assay. Oxidative stress parameters (malondialdehyde (MDA), total thiol molecules (TTM), and total antioxidant capacity (TAC)) were assessed. For the in vivo study, thirty-six male Wistar rats were randomly divided into 6 groups. These groups were normal saline, metformin (200 mg/kg), DIC (50 mg/kg/day), DIC + metformin (50, 100, and 200 mg/kg/day). Histopathological studies and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), albumin, direct and total bilirubin were measured. Also, oxidative stress parameters were assessed in liver tissue. Furthermore, expression of glutathione peroxidase (GPX)-1, -3, and -4, catalase (CAT), superoxide dismutase (SOD)-1, and -3 was examined using the real-time PCR method in hepatic tissue. In the in vitro study, metformin significantly prevented DIC-induced loss in cell viability in HepG2 cells. Metformin markedly reduced DIC-induced elevation of MDA levels and increased the TAC and TTM levels. In the in vivo study, metformin significantly prevented DIC-induced changes in hematological and histological markers. Administration of metformin significantly improved oxidative stress parameters in liver tissue. In addition, metformin increased the expression of antioxidant enzymes. Our results suggest that metformin exerts a significant protective effect against DIC-induced hepatic toxicity.

Investigating the effect of myricetin against arsenic-induced cardiac toxicity in rats.

Arsenic intoxication is a serious health hazard worldwide. Its toxicity is associated with several disorders and health problems in humans. Recent studies revealed that myricetin has various biological effects, including anti-oxidation. The aim of this study is to investigate the protective effect of myricetin against arsenic-induced cardiotoxicity in rats. Rats were randomized to one of the following groups: control, myricetin (2 mg/kg), arsenic (5 mg/kg), myricetin (1 mg/kg) + arsenic, and myricetin (2 mg/kg) + arsenic. Myricetin was given intraperitoneally 30 min before arsenic administration (5 mg/kg for 10 days). After treatments, the activity of lactate dehydrogenase (LDH) and the levels of aspartate aminotransferase (AST), creatine kinase myocardial band (CK-MB), lipid peroxidation (LPO), total antioxidant capacity (TAC), and total thiol molecules (TTM) were determined in serum samples and cardiac tissues. Also, histological changes in cardiac tissue were evaluated. Myricetin pretreatment inhibited arsenic-induced increase in LDH, AST, CK-MB, and LPO levels. Pretreatment with myricetin also enhanced the decreased TAC and TTM levels. In addition, myricetin improved histopathological alterations in arsenic-treated rats. In conclusion, the results of the present study demonstrated that treatment with myricetin prevented arsenic-induced cardiac toxicity at least in part by decreasing oxidative stress and restoring the antioxidant system.