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ABSTRACT: INTRODUCTION: Sulfasalazine (SASP) is a drug commonly used in the treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease (CD) and rheumatoid arthritis (RA). A high incidence of side effects limits therapy with this drug. Getting a wider knowledge of drug pharmacology, indications and side effects is essential to ensure the best possible clinical care, minimizing toxicity and inappropriate use. AREAS COVERED: This paper gives an overview of recent research about SASP and its main adverse effects, highlighting the mechanisms underlying them. To give an overview and comment on the data available so far on this topic, relevant literature was identified using a PubMed search of articles published up to December 2009. Search terms included: 'sulfasalazine', 'oxidative stress, 'renal effects', 'hepatotoxicity' and 'male fertility'. Original papers were reviewed and relevant citations from these articles were also considered. EXPERT OPINION: Although SASP and 5-aminosalicylic acid also scavenge ROS, which may account for some of their anti-inflammatory properties, the reaction with ROS may also generate toxic free radicals; hence, the ability of other antioxidants to suppress the toxicity of SASP in vivo. Further investigations, particularly about SASP mechanism, are still needed.
Expert Opinion on Drug Safety 03/2011; 10(2):253-63. · 3.02 Impact Factor
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ABSTRACT: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants. Although developmental neurotoxicity of PBDEs has been already investigated, little is still known about their potential neurotoxic effects in adulthood. In this study, we assessed the oxidative damage in brain sections and the possible behavioral effects induced by exposure to 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Adult male rats (10/group) received BDE-99 by gavage at single doses of 0, 0.6 or 1.2mg/kg/body weight. Forty-five days after exposure, the following behavioral tests were conducted: open-field activity, passive avoidance and Morris water maze. Moreover, cortex, hippocampus and cerebellum were processed to examine the following oxidative stress (OS) markers: 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). In cerebellum, BDE-99 significantly decreased SOD, CAT and GR activities at the highest BDE-99 dose. A decrease in CAT and SOD activities was also observed in cortex and hippocampus, respectively. In the behavioral tests, no BDE-99 effects were observed, while histopathological examination of the brain regions was normal. The current results show that the brain antioxidant capacity is affected by BDE-99 exposure, mainly in cerebellum. Oxidative damage could be a mechanism for BDE-99 neurotoxicity in adult rats.
Toxicology Letters 04/2010; 194(1-2):1-7. · 3.23 Impact Factor
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ABSTRACT: Little is known about the potential toxicity of polybrominated diphenyl ethers (PBDEs) on hepatic and renal tissues. In this study, we investigated the modifications in endogenous antioxidant capacity and oxidative damage in liver and kidney of rats by exposure to one of the most persistent PBDE congeners, the 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Adult male rats (10 per group) received BDE-99 by gavage at a single dose of 0, 0.6, and 1.2mg/kg body weight. Forty-five days after exposure, liver and kidney were removed and processed to examine the following oxidative stress (OS) markers: 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). In liver, BDE-99 significantly increased SOD activity, GSSG levels, and GSSG/GSH ratio, while GSH levels decreased. Moreover, CAT activity was only reduced at the highest BDE-99 dose. In kidney, CAT activity was significantly decreased, while GSSG/GSH ratio significantly increased following BDE-99 exposure at 1.2mg/kg body weight. Histological examination of tissues showed phagolysosomes in the kidneys of BDE-99-exposed rats. The results of this investigation suggest that acute oral BDE-99 exposure causes renal and liver impairment, being oxidative damage a potential mechanism for nephrotoxicity and hepatotoxicity.
Toxicology 03/2010; 271(1-2):51-6. · 3.68 Impact Factor
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ABSTRACT: The mechanism of action of sulfasalazine (SASP) in male infertility is not well elucidated. For it, an oxidative stress-like mechanism inductor of infertility was hypothesized. Adult male Sprague-Dawley rats (20/group) were orally administered 0, 300, and 600mg SASP/kg body weight for 14 days. One-half of animals in each group remained an additional period of 14 days without treatment. SASP induced a significant decrease of superoxide dismutase (SOD) and glutathione reductase (GR) at the highest dose in both testis and epididymis. GR remained altered in these tissues within the recovery period. However, an increase in SOD was noted in epididymis. An increase in thiobarbituric acid-reactive substances (TBARS) was noted in all SASP-treated groups. In epididymis, catalase (CAT) significantly increased at 600mg/(kgday). These results suggest that SASP induces oxidative stress, which in turn might act as a possible mechanism of male-induced infertility.
Reproductive Toxicology 12/2008; 27(1):35-40. · 3.23 Impact Factor
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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.
Toxicology.
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ABSTRACT: In this study, we evaluated the effects of BDE-99 on hormone homeostasis, as well as in urinary and serum biochemical parameters of adult male rats. Animals (10 per group) received BDE-99 by gavage at single doses of 0, 0.6 and 1.2mg/kg. Forty-five days after BDE-99 exposure, urine and serum samples were collected for hormonal and biochemical analysis. Oxidative stress (OS) markers in erythrocytes, plasma and urine were also evaluated. Urinary excretion of total protein significantly increased following BDE-99 exposure, while lactate dehydrogenase (LDH), gamma-glutamil transferase (GGT), and N-acetylglucosaminidase (NAG) activities significantly decreased. Liver toxicity was evidenced by elevated serum activities of the enzymes glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP). Following BDE-99 administration, OS markers in erythrocytes showed an increase in superoxide dismutase (SOD) activity, and a reduction in glutathione reductase (GR) activity. In urine, isoprostane levels increased after BDE-99 exposure. The hormonal analysis showed a significant decrease in testosterone and progesterone levels. These results support the hypothesis that BDE-99 interacts with hormonal response. Moreover, BDE-99 administration to adult male rats showed signs of renal and hepatic toxicity.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 48(8-9):2206-11. · 2.99 Impact Factor
