Akademik Veri Yönetim Sistemi
Biological Trace Element Research, 2026 (SCI-Expanded, Scopus)
This study aimed to comprehensively evaluate the effects of eugenol (EUG) on oxidative stress, inflammation, ferroptosis, endoplasmic reticulum (ER) stress, autophagy, and apoptosis in an experimental nephrotoxicity model induced by mercury chloride (HgCl₂). Thirty male Sprague–Dawley rats were divided into five groups: control, EUG (100 mg/kg), HgCl₂ (1.23 mg/kg), HgCl₂+EUG50, and HgCl₂+EUG100. HgCl₂ was administered intraperitoneally, and EUG was administered orally for 7 days. Oxidative stress and inflammation parameters in kidney tissues were evaluated by ELISA; histopathological changes were evaluated by H&E and Masson’s Trichrome staining; ferroptosis markers (GPx4, ACSL4, FTH1) were evaluated immunohistochemically; and DNA oxidative damage (8-OHdG) was evaluated by immunofluorescence. Apoptosis-related proteins were analyzed by Western blot, while autophagy and ER stress-related genes were analyzed by RT-qPCR. HgCl₂ administration increased MDA levels in kidney tissue while significantly decreasing GSH and SOD levels; proinflammatory cytokines (TNF-α, IL-1β, IL-6) increased while IL-10 levels were suppressed. Histopathologically, marked tubular degeneration, necrosis, and fibrosis developed. In the HgCl₂ group, GPx4 and FTH1 expression decreased, while ACSL4 and 8-OHdG levels increased. Bax and caspase-3 protein levels were elevated, and Bcl-2 was suppressed. Additionally, autophagy (Beclin-1, LC3A/B) and ER stress (eIF2α, ATF4, CHOP, IRE1) gene expressions were significantly elevated. EUG administration, particularly at a dose of 100 mg/kg, significantly improved these alterations; it reduced oxidative stress and inflammation, attenuated ferroptosis and ER stress–related alterations, and regulated apoptosis and autophagy responses. The findings reveal that eugenol exhibits a multi-pathway protective profile against HgCl₂-induced kidney damage, acting as an antioxidant, anti-inflammatory, and modulator of cellular stress responses. Eugenol represents a promising therapeutic candidate against heavy metal-induced nephrotoxicity.