Inhibition of NF-κB Pathway by Guggulsterone in the Protective Effects of Cyclophosphamide-Induced Renal Toxicity


Cyclophosphamide which acts as cytotoxic alkylating agent can induce a renal damage through the toxic metabolites which result from metabolic activation of Cyclophosphamide by cytochrome P-450 inside hepatocyte and develop renal toxicity by direct binding with cellular organelles in the urinary tract cells. Guggulsterone is a sterol derived from plant has ability to bind to farsenoid X receptor, mineral corticosteroid receptor, androgen receptor, glucocorticoid receptor and estrogen receptor. It efficiently decreases the pro-inflammatory response by downregulate some of genes that implicate in production and regulation of interleukins (IL-2, IL-4, IL-6 and TNF-α). In this study, the albino rats were divided to four groups: control group treated with vehicle, cyclophosphamide group, cyclophosphamide with guggulsterone group and guggulsterone alone group. Guggulsterone doses were administered orally (25 mg/kg/day) for 8 consecutive days while the cyclophosphamide (150 mg/kg) was administered intraperitoneal at day 5 of experiment. At the end of experiment, the kidney index and the serum level of tumor necrosis factor (TNF-), urea and creatinine were determined, also the NF-κB P65 and catalase tissue activities were measured with histopathological assessment. The daily dose of guggulsterone produced a significant reduction in the serum level of TNF-a, urea, creatinine, and tissue activities of NF-κB, and catalase enzyme. The histological feature was also improved. These data represent the protective effect of guggulsterone against the cyclophosphamide renal toxicity.