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

Background: 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.

Aims: 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.

Main Method: 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.

Key Findings: 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.

Significance: 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.