Cisplatin is one of the most commonly used and highly effective
cancer chemotherapeutic agents. Use of
cisplatin is limited due to persistence of severe side effects such as nephrotoxicity, neurotoxicity, and
hearing loss. Nephrotoxicity is the most common limiting side effect of
cisplatin use.
Zingerone is one of the active ingredients present in ginger plant that has anti-inflammatory and
antioxidant effects. In this study, Wistar rats were assigned randomly to 6 groups with 5 animals in each group. The control group;
cisplatin group which received 7.5 mg/kg of
cisplatin intraperitoneally (i.p.) at the 4th day;
zingerone group received 50 mg/kg of
zingerone orally for 7 days. Three other groups were pretreated with 10, 20, and 50 mg/kg of
zingerone orally for 7 days and
cisplatin administered 7.5 mg/kg i.p. at the 4th day, respectively. The animals were sacrificed 72 h after
cisplatin injection and blood samples were taken to evaluate the serum factors. Right kidneys were collected for histopathological studies and left kidneys were considered to measure the oxidative stress parameters and TNF-α
cytokine. Co-administration of
zingerone along with
cisplatin resulted a statistically significant reduction in
lactate dehydrogenase (LDH) activity,
creatinine and BUN levels of serum in comparison with
cisplatin alone group (P < 0.01).
Zingerone significantly decreased the tissue levels of
malondialdehyde (MDA) (P < 0.05) and significantly retained the
enzyme activity of
catalase (CAT) (P < 0.05) and
glutathione peroxidase (GPX) (P < 0.05) in kidney tissue compared to
cisplatin.
Zingerone did not permit the reduction of
glutathione (GSH) levels (P < 0.001) in kidney tissue and by reducing the level of
tumor necrosis factor (TNF)-α (P < 0.05) suppressed the
inflammation produced by
cisplatin. Furthermore,
zingerone improved histopathological changes such as vacuolation (fat deposit), brush border loss, infiltration of leukocytes, glomerular diameters and congestion of RBCs. However, our findings suggest that
zingerone has nephroprotective effects in
cisplatin rat model of nephrotoxicity mostly through suppression of oxidative stress and
inflammation.