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

GEZER A., ÜSTÜNDAĞ H., Karadağ Sarı E., Bedir G., GÜR C., Mendil A. S., ...Daha Fazla

Food and Chemical Toxicology, cilt.193, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 193
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.fct.2024.115040
  • Dergi Adı: Food and Chemical Toxicology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, Environment Index, Food Science & Technology Abstracts, Pollution Abstracts, Veterinary Science Database
  • Anahtar Kelimeler: Alpha-amanitin, Antioxidants, Nephrotoxicity, Oxidative stress, β-carotene
  • Atatürk Üniversitesi Adresli: Evet

Özet

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.