Protective Effects of Vanillic Acid on Arsenic-Induced Hepatotoxicity and Diabetes in Mice; the Role of PPARγ and NF-κB Signaling.

Background: Arsenic (As), a toxic metalloid present in drinking water, is one of the environmental pollutants associated with diabetes in humans. Vanillic acid (VA), a bioactive compound derived from plants has various medicinal activities. Methods: This study was conducted on NMRI male mice for 8 weeks. forty mice were randomly divided into control group, As group (50 ppm), VA (100 mg/kg) group, and two groups receiving As (50 ppm) and VA with doses of 50 mg/kg and 100 mg/kg. After 56 days of the study, the mice were fasted overnight and on day 57, fasting blood glucose was measured, and glucose tolerance test was performed. On day 59, mice were euthanized and serum factors, markers of oxidative stress, tumor necrosis factor-α (TNF-α), and expression nuclear factor kappa B (NF-κB) and Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) proteins were measured. Results: The As significantly increased fasting blood sugar, the activity level of liver function enzymes, thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), TNF-α, and NF-κB expression. Furthermore, As decreased hepatic total thiol (TT) and activity levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and expression of PPARγ. VA decreased the altered liver enzymes, hyperglycemia, NO, TBARS, TNF-α and the expression of NF-κB. Furthermore, increased the hepatic activity of the CAT, SOD, and GPx, TT and the expression of PPARγ. Conclusions: The administration of VA at doses of 50 and 100 mg/kg demonstrated significant mitigation of the toxic effects induced by As on the liver.