The 2nd International Conference on Drug Discovery & Therapy: Dubai, February 1 - 4, 2010


Poster Presenter

Sulfasalazine-Induced Oxidative Stress in Rats
Domingo J. Sánchez, Virginia Alonso, Maria L. Albina, Montserrat Bellés, M. Victoria Linares, Jose L. Domingo
Spain

Sulfasalazine (SASP) is a commonly used drug in the treatment of inflammatory bowel diseases (IBD). SASP treatment can cause adverse side effects in renal and hepatic tissues, although its main toxicity is related to male infertility. In this study, we investigated the changes in endogenous antioxidant capacity and oxidative damage in liver, kidney, testis and epididymis of SASP-treated rats. Adult male SD rats were orally given 0, 300, and 600 mg SASP/kg body weight for 14 days. One half of the animals in each group remained 14 additional days without SASP treatment. At the end of the experimental period, animals were euthanized and liver, kidney, testis and epididymis removed. In these organs, the following stress markers were determined: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid-reactive substances (TBARS). Histological examination of kidneys showed phagolysosomes after 14 days of SASP withdrawal. A dropsical degeneration was also observed in kidney. Oral SASP administration induced a significant increase in renal and hepatic TBARS levels. After 2 weeks without SASP administration, a recovery of these levels was noted. SOD activity was significantly reduced, while CAT activity significantly increased at 600 mg SASP/kg/day. In kidney, GPx activity significantly increased, whereas GST activity and GSH levels were significantly reduced at 600 mg SASP/kg/day. In testis and epididymis, SASP induced a significant decrease of SOD and GR at 600 mg/kg, while GR remained altered in these tissues within the recovery period. However, increases in SOD and TBARS were noted in epididymis of all SASP-treated groups, where CAT also significantly increased at 600 mg/kg/day. In rats, oxidative damage can be a possible mechanism of male-induced infertility














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