IMPACT OF DEHYDROEPIANDROSTERONE IN PREVENTION OF PARACETAMOL INDUCED NEPHROTOXICITY IN RATS

Abstract

Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mecha nisms mediating the event. However, Dehydroepiandrosterone (DHEA), the major secretory product of the human adrenal gland, has been shown to possess a multi-ta rgeted antioxidant activity which is also effective against lipid peroxidation induced in various animal models and against various human disorders. In this study, the preventive effect of DHEA against PCM-induced nephrotoxicity was examined. Rats were divided into four groups containing 10 rats each, as follows: A control: Rec eived normal saline, Vehicle treated: Received the vehicle (5% DMSO), PCM model (750 mg kg -1 ), PCM and DHEA treated: Received concomitant dose of PCM (750 mg kg -1 ) + DHEA (250 mg kg -1 ), respectively, for 4 consecutive weeks. All treat ment were given orally to animals. Our results show that co-treatment of DHEA with PCM prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced b y a significantly reduced (p<0.05) level of serum c reatinine, urea and BUN with parallel significant increases in serum protein, Cr clearance and kidneys weights. Furthermore, DHEA was able to induce a significant increment (p<0.05) of renal levels of reduced Gluta thione (GSH) and activities of Superoxide Dismutase (SOD) and Glutathione Peroxidise (GPx). An effect that wa s accompanied with a significant decrease in renal li pid peroxides levels (MDA). The nephroprotective effects of DHEA was confirmed by a reduced intensity of renal cellular damage, as evidenced by histological findi ngs. In conclusion, DHEA at a daily dose of 250 mg kg -1 has a protective role against PCM-induced nephroto xicity in