Lipid peroxidation and antioxidant status in kidney and liver of rats treated with sulfasalazine.
Sulfasalazine (SASP) is a drug commonly used in the treatment of inflammatory bowel diseases (IBD). In this study, the changes in endogenous antioxidant capacity and oxidative damage in liver and kidney of SASP-treated rats were investigated. Adult male Sprague-Dawley rats were orally given 0, 300, or 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, rats were euthanized and liver and kidney were removed. In both 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). Moreover, histological examination of kidneys showed phagolysosomes after 14 days of SASP withdrawal. A dropsical degeneration was also observed in renal tissue. Oral SASP administration induced a significant increase in TBARS levels in both liver and kidney. 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, while GST activity and GSH levels were significantly reduced at 600 mg SASP/(kg day). These results suggest that in male rats, oxidative damage can be a mechanism for nephro- and hepatotoxicity related with SASP treatment.
Linares
Victoria
V
Laboratory of Toxicology and Environmental Health, School of Medicine, Rovira i Virgili University, Sant Llorens 21, 43201 Reus, Catalonia, Spain.
Alonso
Virginia
V
Albina
Maria L
ML
Bellés
Montserrat
M
Sirvent
Juan J
JJ
Domingo
José L
JL
Sánchez
Domènec J
DJ
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012460:Sulfasalazine / Q000008:administration & dosage / Q000009:adverse effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D012460:Sulfasalazine