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

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

Dergi

FOOD AND CHEMICAL TOXICOLOGY

Yıl

2024

Cilt

193

ISSN

0278-6915

eISSN

1873-6351

DOI

10.1016/j.fct.2024.115040

WoS UID

WOS:001339177200001