β-carotene protects against α-amanitin nephrotoxicity via modulation of oxidative, autophagic, nitric oxide signaling, and polyol pathways in rat kidneys

Alpha-amanitin (α-AMA), a toxic component of Amanita phalloides, causes severe hepato- and nephrotoxicity. This study investigated the protective effects of βeta-carotene (βC) against α-AMA-induced kidney damage in rats. Thirty-two male Sprague-Dawley rats were divided into four groups: Control, βC (50 mg/kg/day), α-AMA (3 mg/kg), and βC+α-AMA. βC was administered orally for 7 days before α-AMA injection. Renal function, oxidative stress markers, histopathological changes, and enzyme activities were evaluated 48 h post-α-AMA administration. α-AMA significantly increased serum creatinine and urea levels, decreased glutathione and catalase activity, and increased malondialdehyde levels (P < 0.001). βC pretreatment attenuated these changes (P < 0.05). Histopathological examination revealed reduced tubular degeneration in the βC+α-AMA group (P < 0.001). Immunohistochemical analysis showed increased LC3B and Beclin-1 expression in α-AMA-treated rats, indicating enhanced autophagy, partially reversed by βC. Additionally, α-AMA reduced nitric oxide synthase (NOS) activity and increased aldose reductase (AR) activity, both normalized by βC pretreatment (P < 0.01). βC demonstrates protective effects against α-AMA-induced nephrotoxicity through antioxidant action, modulation of autophagy, and regulation of NOS and AR pathways, suggesting its potential as a therapeutic agent in α-AMA poisoning. © 2024 Elsevier Ltd