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The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed to measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-alpha level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics.

Background: Peritoneal adhesions are pathological fibrotic bands developing after mesothelial damage. Transforming growth factor beta-1 (TGF-beta1) has mitogenic activities for macrophages and fibroblasts. Over-expression of TGF-beta1 has been implicated in the pathogenesis of several fibrotic disorders. Angiotensin II increases the expression of the TGF-beta1 in fibroblasts. The aim of the study was to investigate the effect of angiotensin converting enzyme inhibitor (ACE) on intraperitoneal adhesions., Materials and Methods: Thirty male Wistar albino rats were divided into two groups. In the first procedure, laparotomy was performed through a 3-cm midline incision. Ileum was divided above 10 cm from ileocecal valve and a single-layer ileoileal anastomosis was performed. Although no treatment was given to rats in group 1, lisinopril (an ACE inhibitor) was given to rats in group 2 for postoperative 7 days in drinking water. Estimated amount of supplied lisinopril was 6.5 mg/kg/day. On postoperative 8th day, relaparotomy was performed and adhesions were evaluated. At the same time, blood samples were taken for TGF-beta1 measurements., Results: Adhesion severity was significantly less in the ACE inhibitor group (P < 0.001). While mean TGF-beta1 level was 860.3 +/- 108.1 pg/dl (mean +/- SD) in control group, it was 335.8 +/- 52.4 pg/dl in ACE inhibitor group (P < 0.001). There was a significant correlation between serum TGF-beta1 levels and grade of adhesions (r = 0.948)., Conclusion: It was concluded that ACE inhibitors might be useful for preventing peritoneal adhesions.