Background: Methotrexate (MXT) is the corner stone in treatment of rheumatoid arthritis. Although methotrexate is usually administrated in low weakly dose in patients with rheumatoid arthritis discontinuation rates are as high as 16% due to adverse effects. Hepatotoxicity is the most common side effect after long term course of methotrexate.
Aim of the study: This work aimed to investigate the potential effect of sitagliptin alone and in combination with different doses of methotrexate on rheumatoid arthritis (RA) induced experimentally in rats. Moreover, we investigated the benefits of sitaglipitn co-administration with methotrexate not only on RA progression, but also on organs commonly injured on using methotrexate alone as a disease-modifying anti-rheumatic drug such as the liver.
Methods: 42 male adult Sprague Dawley rats divided into seven equal groups: Normal control group, None treated Freund,s adjuvant induced rheumatoid arthritis,High dose MXT treated rheumatoid arthritis (1 mg /kg /3 days i.p.) over 4 weeks,Sitagliptin treated rheumatoid arthritis (10 mg /kg / day p.o) for 4 weeks, high dose MXT+ sitagliptin treated arthritis, 1/2 dose MXT+ sitagliptin treated arthritis, 1/4 dose MXT + sitagliptin treated arthritis. Serological parameters namely, cyclic citrullinated peptide antibodies (Anti-CCP), matrix metalloproteinase -3(MMP-3), cartilage oligometric matrix protein (COMP) and TNF-α level were measured. Liver tissue and hind paw joint were subjected to histopathological examination.
Results: Best degree of improvement was obtained with high dose MXT+ sitagliptin. It is significantly better than that of either drug alone. Half dose of MXT /sitagliptin combination was proved to be equally effective to the full dose of methotrexate alone regarding all tested parameters.
Conclusion: concomitant administration of sitagliptin augmented immunosuppressive effect and ameliorated hepatotoxicity of methotrexate in Freund,s adjuvant model of rheumatoid arthritis.