Journal of Cancer Research and Therapeutics

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


Erkan Cure1, Aynur Kirbas2, Levent Tumkaya3, Medine Cumhur Cure2, Yildiray Kalkan3, Arif Yilmaz4, Suleyman Yuce1 
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

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.


How to cite this article:
Cure E, Kirbas A, Tumkaya L, Cure MC, Kalkan Y, Yilmaz A, Yuce S. Protective effect of infliximab on methotrexate-induced liver injury in rats: Unexpected drug interaction.J Can Res Ther 2015;11:164-169


How to cite this URL:
Cure E, Kirbas A, Tumkaya L, Cure MC, Kalkan Y, Yilmaz A, Yuce S. Protective effect of infliximab on methotrexate-induced liver injury in rats: Unexpected drug interaction. J Can Res Ther [serial online] 2015 [cited 2019 Oct 14 ];11:164-169
Available from: http://www.cancerjournal.net/article.asp?issn=0973-1482;year=2015;volume=11;issue=1;spage=164;epage=169;aulast=Cure;type=0