Zingerone ameliorates gentamicin-induced nephrotoxicity in rats

Gentamicin (GEN) is an antibiotic to treat severe gram-negative infections. Nephrotoxicity is the major adverse effect limiting clinical use of GEN. Zingerone (ZIN), an important component of ginger root, has several pharmacological effects including antioxidant, anti-inflammatory, and free radical scavenging activity. The present study investigated the effects of ZIN against GEN-induced nephrotoxicity. Twenty-eight rats were randomly divided into four groups: group I received normal saline, group II was treated with GEN (100 mg/kg/day, i.p.), group III was treated with ZIN (10 mg/kg/day, orally) and GEN (100 mg/kg/day, i.p.), and group IV was treated only with ZIN (10 mg/kg/day, orally). The level of creatinine (Cr), blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) was assessed in the serum of animals. The content of protein carbonylation (PC), malondialdehyde (MDA), nitric oxide (NO^•), and glutathione (GSH) and the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT), as well as histopathological parameters were evaluated in the kidney tissues. Treatment with ZIN (10 mg/kg/day) remarkably improved GEN-induced alteration in histopathological parameters; these protective effects were associated with the reduction in GEN-induced elevation in the serum level of Cr, BUN, NGAL, and KIM-1. Zingerone also reduced MDA, PC, and NO^• levels as well as increased GSH content and SOD and CAT activity in the kidney tissues. Our results suggest that ZIN may inhibit GEN-induced nephrotoxicity through scavenging reactive free radicals and increasing intracellular antioxidant capacity.