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ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 1  |  Page : 164-169

Protective effect of infliximab on methotrexate-induced liver injury in rats: Unexpected drug interaction


1 Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
2 Department of Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
3 Department of Histology and Embryology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
4 Department of Gastroenterology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey

Correspondence Address:
Erkan Cure
Department of Internal Medicine, University of Recep Tayyip Erdogan, School of Medicine, Rize, 53100
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.140809

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Aims: Although methotrexate (mtx) is a widely used agent to treat cancer and inflammatory diseases, its hepatotoxic effect limits for clinical utility. We aimed to investigate whether infliximab (inf), an inhibitor of tumor necrosis factor-alpha (TNF-α) has a protective effect against mtx-induced hepatotoxicity. Materials and Methods: For mtx group, the animals received an intraperitoneal single dose injection of mtx at a dose of 20 mg/kg. For inf group, the animals received an intraperitoneal single dose injection of inf at a dose of 7 mg/kg. For mtx + inf group, the single dose of inf at a dose of 7 mg/kg was given 72 h prior to mtx injection. After 72 h, a single dose of mtx 20 mg/kg was given. All rats were sacrificed 5 days after mtx injection. Results: TNF-α and nitric oxide (NO) levels of mtx group was significantly higher than the control (P < 0.001), inf (P < 0.001) and mtx + inf (P < 0.001) groups. Total score of histological damage was higher in the mtx group when compared with the mtx + inf group. Arginase and carbamoyl phosphate synthetase 1 (CPS-1) of mtx group was suppressed in comparison with the control group and was markedly increased in mtx + inf group. Conclusion: Inf may partially prevent mtx-induced hepatic damage in rats. However, the combined usage of mtx and inf increases arginase and CPS-1 enzyme activities and at the same time blocks TNF-α. This combination especially in cancer patients may lead to cancer cell invasion and metastasis.


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