Therapeutic effects of biochanin A, phloretin, and epigallocatechin-3-gallate in reducing oxidative stress in arsenic-intoxicated mice.

ABSTRACT

One of the most common toxicant prevailing in our environment is the arsenic. The present study is an attempt to investigate the effects of some of the common flavonoids, such as biochanin A (BCA), phloretin, and epigallocatechin-3-gallate (EGCG), on arsenic toxicity in the Swiss albino mice. For this purpose, mice were orally treated with sodium meta-arsenite (20 mg/kg bw/day), along with co-administration of BCA (50 mg/kg bw/day), phloretin (50 mg/kg bw/day), and EGCG (40 mg/kg bw/day) for the 2-week duration. All the mice were euthanized at the end of the treatment period, and the observations were made in the following parameters. Arsenic reduced the sperm motility as compared with the control (p < 0.05) and was restored back to the normal status with the flavonoids treatment significantly (p < 0.05). The arsenic concentrations in the kidney and liver tissues were found significantly reduced with all the flavonoids co-treatment (p < 0.001). There was a reduction in the levels of superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione S-transferase (GST) antioxidant markers, with the increased lipid peroxidation (LPO), protein carbonyl content (PCC), and catalase (CAT) levels in the arsenic-intoxicated mice performed in the different tissues. The biochemical homeostasis alterations were well correlated with the estimations of cholinesterase enzyme levels in the brain tissues (p < 0.05) along with DNA damage analysis (Comet) carried out in the blood cells (p < 0.05). These above results are well corroborated with the histopathological findings performed in the brain tissue, along with the increased upregulation seen in the Nrf2 signalling, with all the flavonoid co-treatment carried in the kidney tissue. The administration of BCA, phloretin, and EGCG, in a major way, reversed the alterations in the abovementioned parameters in the arsenic-intoxicated mice. Our findings revealed the beneficial effects of the flavonoids against the arsenic-induced toxicity, due to their ability to enhance the intracellular antioxidant response system by modulating the Nrf2 signaling pathway.