Agha A M, Mansour M
Pharmacology Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt.
Toxicol Appl Pharmacol. 2000 Oct 15;168(2):123-30. doi: 10.1006/taap.2000.8985.
We previously demonstrated that captopril (CP) exhibited a high ability to inhibit enzymatically generated leukotrienes, particularly LTB(4), 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) LTB(4) and IL-6 levels. The effect on LTB(4) 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 LTB(4) and IL-6.
我们之前证明，卡托普利（CP）对酶促生成的白三烯，尤其是LTB4，具有高度抑制能力，该能力源于对受刺激的完整人中性粒细胞的作用。这一发现连同CP的免疫抑制作用，提示了该药可能具有抗炎活性。因此，本研究旨在探究CP对免疫介导的慢性炎症的影响；选用了两种模型，即弗氏佐剂性关节炎和大鼠混合型超敏反应。根据物理参数（爪肿胀）以及血液和炎性渗出液中的生化标志物来评估CP的作用。在炎症发展过程中每日给予CP。通过腹腔注射给予三个剂量，即1、10和100mg/kg。结果表明，在疾病的所有阶段，CP均成功抑制了弗氏佐剂性关节炎动物后爪的水肿发展。在炎症的慢性期，在任一模型中，CP均降低了血清和渗出液（局部）中升高的LTB4和IL-6水平。对LTB4的作用在渗出液中更为明显，且呈剂量相关趋势。CP的抗关节炎作用还伴随着血清蛋白巯基水平的升高，同时系统和/或局部升高的脂质过氧化物、超氧化物歧化酶和谷胱甘肽水平降低或恢复正常。可以得出结论，长期使用CP对大鼠关节炎具有良好的抗炎活性，可改善关节炎损伤诱导的氧化应激。该药的修复作用可能是通过降低LTB4和IL-6介导的。
