Attenuating effect of bisphosphonate on oxidative responses in rats with adjuvant arthritis

Abstract

Reactive oxygen species are well accepted to play important roles in development and maintenance of several types of diseases, including rheumatoid arthritis and osteoporosis as the final effector molecules. Although it is also reported the anti-inflammatory action of bisphosphonates, which is frequently used for the treatment of osteoporosis, the influence of bisphophonate on the development of oxidative responses. The present study, therefore, was designed to examine the influence of bisphosphonate on oxidative responses through the choice of etidronate (ER) and adjuvant arthritic rats in vivo. Adjuvant arthritis was induced in male Lewis rats by a single subcutaneous injection of 0.1 ml complete Freund's adjuvant into the right hind paw. Treatment of rats with ER was started on day 7 after adjuvant injection. Oxidative responses were evaluated by measuring hydroperoxide contents in plasma with a newly developed free radical analysis system, FREE. Daily intraperitoneal administration of ER for 2 weeks could suppress hydroperoxide contents in plasma, which was increased by adjuvant injection. The minimum dose of the agent, which causes significant suppression of hydroperoxide levels 3.33 mg/kg, a human recommended therapeutic dose. These results may suggest that ER could suppress the production of reactive oxygen species and results in attenuation of the clinical conditions of disease with bone destruction. [J Physiol Sci. 2006;56 Suppl:S239]