The protection afforded by Berberine against chemotherapy-mediated nephropathy in rats involves regulation of the antioxidant axis.

Abstract

Doxorubicin (DOX) treatment in cancer patients leads to nephrotoxicity. The nephroprotective effect of Berberine (BBR), a herbal ingredient, is well documented as antioxidant and activation of the Nrf2 signalling. This study aimed to investigate if Nrf2 is a major protective mechanism of BBR in DOX animal models. Rats were divided as (n = 6 each): Control, BBR (100 mg/kg, orally), DOX (15 mg/kg, orally), BBR + DOX, and BBR + DOX + brusatol (0.2mg/kg, i.p./twice per week) (an Nrf2 inhibitor). DOX was given as a single dose (day 10), whereas BBR was administered for 3weeks on a daily basis. BBR reduced tubular degeneration and improved renal markers in DOX-treated rats. It also reduced renal nuclear levels of NF-κB p65, total reactive oxygen species (ROS), lipid peroxides, interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α), as well as mRNA levels of Bax and cleaved caspase-3. However, BBR stimulated glutathione (GSH) and superoxide dismutase (SOD) levels, the transcription of Bcl2, and the mRNA, total cytoplasmic, and nuclear levels of Nrf2 with no effect on the cytoplasmic keap1 levels. All these effects disappeared by brusatol. In conclusion, BBR prevents DOX-induced renal damage by activating Nrf2.