Cuzzocrea S, Costantino G, Mazzon E, Zingarelli B, De Sarro A, Caputi A P
Institute of Pharmacology, University of Messina, Italy.
Biochem Pharmacol. 1999 Jul 1;58(1):171-6. doi: 10.1016/s0006-2952(99)00067-2.
In the present study we investigated the therapeutic efficacy of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimetic which possesses peroxynitrite scavenging effects, in rats subjected to carrageenan-induced paw oedema. Local administration of MnTBAP (5, 25, and 50 microg/paw) significantly and dose dependently reduced carrageenan-induced paw oedema at all time points. MnTBAP also caused a significant dose-dependent reduction in paw myeloperoxidase activity and lipid peroxidation, as well as preventing histological injury. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in paw from carrageenan-treated rats. No positive nitrotyrosine staining was found in the paws of the carrageenan-treated rats that received MnTBAP. Our study demonstrates that MnTBAP exerts protective effects in carrageenan-induced paw oedema. Part of these anti-inflammatory effects may be related to: 1) reduction of superoxide formation due to the superoxide dismutase-like activity of the compound; and 2) scavenging of peroxynitrite.
在本研究中,我们调查了四(4 - 苯甲酸)锰卟啉(MnTBAP)的治疗效果,MnTBAP是一种具有超氧化物歧化酶活性且能清除过氧亚硝酸盐的模拟物,用于角叉菜胶诱导的大鼠爪肿胀实验。局部给予MnTBAP(5、25和50微克/爪)在所有时间点均显著且剂量依赖性地减轻了角叉菜胶诱导的爪肿胀。MnTBAP还显著剂量依赖性地降低了爪部髓过氧化物酶活性和脂质过氧化,并防止了组织学损伤。对硝基酪氨酸的免疫组织化学分析显示,角叉菜胶处理的大鼠爪部呈阳性染色。在接受MnTBAP的角叉菜胶处理大鼠的爪部未发现硝基酪氨酸阳性染色。我们的研究表明,MnTBAP对角叉菜胶诱导的爪肿胀具有保护作用。这些抗炎作用部分可能与以下因素有关:1)由于该化合物的超氧化物歧化酶样活性而减少超氧化物的形成;2)清除过氧亚硝酸盐。