Ameliorative Effect of Linagliptin Alone and in Combination with Methotrexate against Formaldehyde Induced Arthritis in Rats: Biochemical and Histopathological Study

Background: The hallmark of rheumatoid arthritis (RA), is the inflammatory cells infiltration into hyperplastic synovial tissue that leads to the eventual degeneration of bone and articular cartilage. The first traditional disease-modifying anti-rheumatic medication, methotrexate (MTX), is linked to immune responses and may reduce articular damage in RA. Effective half- of therapeutic dose of MTX is essential due to its numerous undesirable side effects. Aim and methods: The anti-arthritic effects of linagliptin (LIN) at 5 mg/kg/day oral starting at day 4 after injection with formaldehyde (2% v/v) into the subplanter surface of a left hind paw at 1 and 3 days of the study for four weeks was evaluated alone, and in combination with a half-dose of MTX (1 mg per kg body weight IP once weekly). Serum level of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), C-reactive protein (CRP), oxidative stress mediators, and serum apoptotic markers were assessed. Moreover, hind paw histopathology and cyclooxygenase (COX) expression by IHC were examined in this study. Results: Rats treated with both half -dose of MTX and LIN showed better results as full dose MTX arthritic-treated rats, and is superior if compared to LIN alone. Combined therapy exhibited improvement of all above mentioned parameters. Furthermore, the rats received dual therapy demonstrated improvement of histopathological alterations. Conclusion: Combination of LIN and half -dose of MTX has synergetic effect so, it is beneficial in the management of RA as the standard group (full dose of MTX).