Effects of captopril on interleukin-6, leukotriene B4, and oxidative stress markers in serum and inflammatory exudate of arthritic rats:: Evidence of antiinflammatory activity

We previously demonstrated that captopril (CP) exhibited a high ability to inhibit enzymatically generated leukotrienes, particularly LTB4, from stimulated intact human neutrophils. This finding together with the immunosuppressive effect of CP have proposed a possible antiinflammatory activity for the drug. Thus, the present study was conducted to investigate the effect of CP on immunologically mediated chronic inflammation; two models were chosen, namely, Freund's adjuvant arthritis and mixed-type hypersensitivity in rat. The effect of CP was assessed on the basis of physical parameter (paw edema) and biochemical markers in blood and inflammatory exudate. CP was given daily during the course of inflammation development. It was administered ip at three doses, viz. 1, 10, and 100 mg/kg. The results claimed that CP succeeded in suppressing edema evolution in hind paws of Freund's arthritic animals, during all phases of the disease. During the chronic phase of inflammation, in either model, CP reduced the elevated serum and exudate (local) LTB4 and IL-6 levels. The effect on LTB4 was more pronounced in the exudate and tended to be dose-related. The antiarthritic effect of CP was also accompanied by augmentation of serum level of protein thiols, with reduction or normalization of elevated systemic and/or local levels of lipid peroxide, superoxide dismutase, and glutathione. It could be concluded that long-term treatment with CP confers a good antiinflammatory activity against arthritis in rat, leading to improvement of the oxidative stress induced by the arthritic insult. The reparative effect of the drug could be mediated via reduction of LTB4 and IL-6. (C) 2000 Academic Press.