Antiarthritic and hepatoprotective effect of derinat on adjuvant arthritis in rats

Institute of Experimental and Clinical Medicine of Vilnius University, Vilnius, Lithuania Background: The inclusion of immunomodulators into the schemes of the treatment of autoimmune process, especially under the therapy with immunosuppressive preparations, is motivated because immunological disturbances play an essential role in the pathogenesis of these conditions. The aim of the present study was to provide data regarding the antiarthritic effect of immunomodulator derinat (D) alone and in combination with methotrexate (MTX), to compare the obtained results with the effects of MTX alone, and to evaluate the potential properties of D to reduce the hepatotoxicity of MTX. Materials and methods: 60 Wistar rats with adjuvant arthritis (AA) were treated with D alone in doses of 6 mg/kg or 18 mg/kg, with a combination of either of them with 2 mg/kg of MTX or MTX alone (2 mg/kg). MTX once a week and D five times a week were injected intramuscularly (i. m.). Control group received saline. The duration of experiment was 17 days. Results: Joint swelling and the histological parameters of arthritis in adjuvant-injected paws were significantly suppressed by all kinds of the treatments tested. D was the most effective TNF-α suppressor and accelerator of lymphocyte blasttransformation. MTX and D did not act synergistically and the antiarthritic effect was not aggravated when the treatment was combined. However, D exerted a positive effect on MTX-elicited alterations in liver. Conclusions: Our results have shown that anti-inflammatory and antiarthritic properties of D on AA in rats are comparable to those exerted by low doses of MTX. D attenuated MTX-induced toxicity on liver, suggesting that the use of combined treatment with MTX and D might also be expedient.