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INTRODUCTION: Methotrexate (MTX), used in the treatment of cancerous patients, causes toxicity in the different organs of the body. This study of rosmarinic acid (RA) is as an antioxidant on nephrotoxicity and hepatotoxicity induced by MTX. METHODS: Rats (n = 32) were divided into four groups: sham; MTX; 100 mg\kg RA + MTX; 200 mg/kg RA + MTX. The amount of MTX was 20 mg/kg. 24 hours after injection of the last dose of MTX, the blood samples and kidneys and liver of rats were studied. The aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, serum creatinine were assessed. Tissue antioxidant enzymes and malondialdehyde (MDA) levels were measured. The liver and kidney tissues were histopathologically examined. RESULTS: MTX significantly increased the urea, creatinine, ALT, AST, ALP levels, and renal MDA and significantly decreased renal catalase (CAT), hepatic glutathione (GSH), and hepatic CAT activity. MTX induced necrosis, leukocyte infiltration, eosinophilic casts, glomerular damage in kidney tissue and necrosis, degeneration and cellular vacuolization in liver tissues. RA at 100 mg/kg caused a significant decrease in ALT and AST and at two doses significantly decreased urea, renal MDA, and liver MDA. RA at 200 mg/kg significantly increased the renal CAT and liver GSH. RA in two doses significantly decreased necrosis and Leukocyte infiltration. RA caused a significant decrease in degeneration and cellular vacuolization in liver tissues. CONCLUSIONS: RA with its antioxidant and anti-inflammatory characteristics decreased the MTX induced nephrotoxicity and hepatotoxicity.
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OBJECTIVE: The leukotrienes are inflammatory mediators. In the present study, the analgesic role of local montelukast, a cysteinyl leukotriene receptor antagonist, and the possible involvement of L-arginine/NO/cGMP/KATP channel pathway and PPARγ receptors was assessed in the formalin test in rats. METHODS AND RESULTS: The local administration of montelukast into the hind paw produced dose-related analgesia during both phases of the formalin test. Furthermore, pre-treatment with L-NAME, methylene blue, and glibenclamide prevented montelukast (10 µg/paw)-induced antinociception in both early and late phases of the test. Moreover, the local L-arginine and diazoxide before the sub-effective dose of montelukast (3 µg/paw) produced an analgesic effect. Also, local GW-9662 blocked antinociception induced by montelukast plus pioglitazone (10 µg/paw). CONCLUSION: In conclusion, montelukast produced peripheral analgesia through PPARγ receptors and activation of the L-arginine/NO/cGMP/KATP channel pathway, with potential for a new topical analgesic drug.
