Toxicology 256 (2009) 152–156 Contents lists available at ScienceDirect Toxicology journal homepage: www.elsevier.com/locate/toxicol Lipid peroxidation and antioxidant status in kidney and liver of rats treated with sulfasalazine Victoria Linares a,b , Virginia Alonso a,b , Maria L. Albina a,b , Montserrat Bellés a,b , Juan J. Sirvent c , José L. Domingo a,∗ , Domènec J. Sánchez a,b a Laboratory of Toxicology and Environmental Health, School of Medicine, “Rovira i Virgili” University, Sant Llorens 21, 43201 Reus, Catalonia, Spain b Physiology Unit, School of Medicine, “Rovira i Virgili” University, Sant Llorens 21, 43201 Reus, Catalonia, Spain c Pathology Unit, School of Medicine, “Rovira i Virgili” University, Sant Llorens 21, 43201 Reus, Catalonia, Spain article info Article history: Received 26 October 2008 Received in revised form 7 November 2008 Accepted 10 November 2008 Available online 21 November 2008 Keywords: Sulfasalazine Male rats Kidney Liver Oxidative stress abstract 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. © 2008 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Sulfasalazine (SASP) is a drug commonly used for the treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD) (Gisbert et al., 2007; Nielsen and Munck, 2007). It consists of sulfapyridine (SP) linked to 5-aminosalicylic acid (5-ASA) by an azo bond. 5-ASA is the active therapeutic moiety of SASP, while the most adverse effects are related to SP (Ransford and Langman, 2002). Although the main toxicity of SASP is related to male infertility (Horimoto et al., 2000; Fukushima et al., 2005, 2007), SASP treatment can also cause adverse side effects in renal and hepatic tissues. Hämling et al. (1997) described a decreased renal function in CD patients associated with the SASP treatment, while Dwarakanath et al. (1992) reported two cases of patients with UC treated with SASP, who developed chronic renal failure. Renal biopsy showed histological changes consistent with drug induced chronic intestinal nephritis. ∗ Corresponding author. Tel.: +34 977 759380; fax: +34 977 759322. E-mail address: joseluis.domingo@urv.cat (J.L. Domingo). On the other hand, hepatotoxicity of SASP has also been reported. Liver damage, as an adverse SASP effect, was found in some UC patients (Nakajima et al., 1995), while Rubin (1994) described a simultaneous sudden hepatic failure and necrotizing pancreatitis in a patient 2–3 weeks after initiation of SASP treat- ment. Moreover, Marinos et al. (1992) reported two cases of massive hepatic necrosis associated with SASP. Renal and hepatic damage induced by SASP can be due to several mechanisms. In recent years, a number of studies have investigated the role of free radicals on chemical-induced toxicity. A variety of xenobiotics, such as metals (Bellés et al., 2007; Linares et al., 2007), aminoglycoside antibiotics (Sener et al., 2002), or immunosuppres- sive drugs (Hara et al., 2001) have shown to induce oxidative stress. The imbalance between increased production of free radicals, and the decreased antioxidant capacity, results in a persistent lipid per- oxidation (LPO). LPO is believed to be an important cause of damage to cell membranes (Reiter et al., 2001). Oxidative stress occurs as a result of excessive formation of reactive oxygen species (ROS), an impaired antioxidant system, or both (Sener et al., 2003). Renal injury associated with an increase of oxidative stress has been reported in the clinical and experimental use of some thera- peutic agents (such as vancomycin and glycerol) (Cetin et al., 2007; 0300-483X/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.tox.2008.11.010