Protective Role of Myricetin and Fisetin Against Nephrotoxicity Caused by Lead Acetate Exposure Through Up-Regulation of Nrf2/Ho-1 Signalling Pathway

Abstract

The effect of various flavonoids against oxidative stress and inflammation caused by lead exposure has been investigated. However, the protective effects of myricetin (MYC) and fisetin (FST), which are known to have potent antioxidant properties, against nephrotoxicity caused by exposure to lead acetate (LA), the water-soluble form of lead, have not been investigated. Our study investigated the protective role of these flavonoids against LA intoxication-induced nephrotoxicity. In our study, 42 male rats were used. The rats were randomly selected and divided into 6 groups. These groups were: control, LA (100 g/kg), LA + MYC (100 mg/kg), LA + MYC (200 mg/kg), LA + FST (100 mg/kg) and LA + FST (200 mg/kg). All chemicals were administered daily by gavage for 28 days. According to the experimental protocol, the animals were sacrificed and their kidney tissues were isolated. Serum biochemical parameters, histological examinations, levels of several trace elements, oxidative stress and inflammatory parameters at both biochemical and molecular levels in kidney tissues were examined. After LA administration, tissue lead levels increased and zinc levels decreased. This situation was reversed by MYC and FST treatment. Oxidative stress and inflammatory response were increased in the kidney tissue of LA-treated rats and renal function was impaired. It was observed that both doses of MYC and high dose of FST could prevent nephrotoxicity. Oral administration of both doses of MYC and high dose FST ameliorated the changes in biochemical, oxidative and inflammatory parameters. Restoration of normal renal tissue architecture was also demonstrated by histological studies. MYC and FST were found to have promising biological activity against LA-induced nephrotoxicity, acting by attenuating inflammation and oxidative stress and improving antioxidant status.