Effect of the NSAID nimesulide on the radical scavenger glutathione S-transferase in patients with osteoarthritis of the knee

Abstract

Objective: Osteoarthritis (OA) of the knee is a secondary inflammatory, painful disease of the knee joint with increasing destruction of the articular cartilage. In the inflammatory process the formation of free radicals (reactive oxygen species, ROS) plays a major role in progression of disease and in the subsequent destruction of joint cartilage. The aim of this pilot study was to examine the antioxidative potency of the non-steroidal anti-inflammatory drug (NSAID) nimesulide on glutathione S-transferase (GST), an enzymatic free radical scavenger. In addition, the effects on matrix metalloproteinase MMP-3 and its antagonist tissue inhibitor of matrix-metalloproteinase 3 (TIMP-1) were determined.

Research design and methods: This was an open-pilot study on 20 patients (aged 41-71 years old) suffering from painful OA of the knee, treated for 3 weeks with nimesulide 100 mg b.i.d. Twenty-three healthy subjects (aged 23-57 years), not age matched, served as a comparison group. GST, MMP-3 and TIMP-1 were measured by enzyme-immunoassays. Clinical symptoms and joint function were measured using the WOMAC Index.

Results: During the 3-week treatment period with nimesulide 100 mg b.i.d., both scavenger GST and the TIMP-1/MMP-3 ratio significantly increased. This change was accompanied by significant clinical improvement in terms of pain reduction, stiffness and joint function. Two adverse events occurred possibly related to nimesulide treatment: one case of moderate eyelid swelling, and one case of moderate diarrhea with no abnormality in the endoscopic examination.

Conclusions: These results confirm the antioxidative properties of the study drug, indicating that nimesulide, beside its known anti-inflammatory properties, also shows an evident antioxidative activity that adds further supportive evidence to its key role in the treatment of OA patients (thanks to the absence of degenerative effects on cartilage).