Evaluation of the effect of bromelain on renal toxicity induced by doxorubicin in rats

Although bromelain (BRM) is a natural antioxidant, free radical scavenger and anti-inflammatory agent, its protective role against cell damage caused by doxorubicin (DOX) has not been investigated much. In this study, the effectiveness of bromelain administration against doxorubicin-induced nephrotoxicity was investigated. In the study, 42 male rats were used. The rats were randomly selected and divided into 6 groups. These groups were control, DOX, BRM20 (20 mg/kg/day BRM, p.o.), BRM40 (40 mg/kg/day BRM, p.o.), DOX+BRM20 (20 mg/kg/day BRM, p.o.) and DOX+BRM40 (40 mg/kg/day BRM, p.o.) groups, respectively. The study lasted for a total of 7 days. The control group was not treated and sacrificed at the end of the study. DOX, DOX+BRM20 and DOX+BRM40 groups were administered 15 mg/kg/i.p. single dose of DOX on the 5th day of the study and sacrificed at the end of the study. In addition, all groups except the control and DOX groups were administered BRM orally at the indicated concentrations every day (for 7 days) throughout the study and sacrificed at the end of the study. At the end of the study, rats were anaesthetised and their blood was collected by cardiac punction and kidney tissues were isolated. In serum samples, urea, creatinine and blood urea nitrogen were analysed using a commercial kit in an autoanalyzer. In kidney tissues, malondialdehyde (MDA) level to determine lipid peroxidation, protein carbonyl levels to determine protein oxidation, 8-hydroxy deoxy guanosine (8-OH dG) level to determine DNA oxidation, Superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rx) activities and reduced glutathione (GSH) levels were measured to determine the antioxidant status and nitric oxide (NOx) and prostaglandin E2 (PGE2) levels were measured to observe the inflammatory response. The data obtained were expressed as mean±standard deviation and the data with a p value of 0.05 or less were considered statistically significant. One-way analysis of variance (ANOVA) and Tukey test were used for the evaluation of biochemical parameters. DOX administration impaired renal function tests, increased lipid peroxidation, protein and DNA oxidation and inflammatory response in renal tissue, and weakened the antioxidant defence system. Bromelain administration prevented oxidative stress and inflammation in renal tissue. In conclusion, it was observed that DOX treatment caused damage in the kidney tissue and bromelain administration could prevent the nephrotoxicity. Key Words: Doxorubicin, Nephrotoxicity, Antioxidant, Oxidative stress, Bromelain