10-Dehydrogingerdione ameliorates renal endoplasmic reticulum/oxidative stress and apoptosis in alcoholic nephropathy induced in experimental rats

Chronic alcoholism induces kidney injury (KI), leading to increased mortality in alcoholic hepatitis patients. Endoplasmic reticulum stress (ER) represents the main initiator of kidney diseases and alcoholic nephropathy. We used alcoholic nephropathy rat model followed by 10-dehydrogingerdione (10-DHGD) intake as potential modulator. This is to focus on ER/oxidative stress/inflammatory and apoptotic pathways involvement. Alcoholic nephropathy was induced by alcohol administration (3.7 g/kg/body weight) orally and daily for 45 days. 10-DHGD (10 mg/kg/day) was administered either alone or along with alcohol. Our results demonstrated significant increase in kidney function parameters like f creatinine, urea, uric acid, and blood urea nitrogen (BUN) levels. Renal ER/oxidative stress markers such as cytochrome P450 family two subfamily E member 1 (CYP2E1), C/EBP homologous protein (CHOP), and endoplasmic glucose-regulated protein 78 (GRP-78) demonstrated also significant increase. Inflammatory mediators like nuclear factor-kappa B (NF-kB), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β along with apoptotic marker caspase-3 behaved similarly. Antioxidant molecules like reduced glutathione (GSH), superoxide dismutase (SOD), and catalase demonstrated marked decrease. 10-DHGD administration resulted in significant modulation represented by an enhancement in the kidney functions and the histopathological patterns in a conclusion of its potential to ameliorate the pathological changes (kidney injury) induced by alcohol intake. [Display omitted] •Chronic alcoholism mediated nephrotoxicity in rats.•New insights of chronic alcoholism induced kidney injury.•10-DHGD protects against alcohol induced neuropathy via inhibition of renal endoplasmic reticulum /oxidative stress /inflammatory and apoptotic pathways.