de Oliveira Carolina C, de Oliveira Simone M, Godoy Lyris M F, Gabardo Juarez, Buchi Dorly de F
Laboratório de Estudos de Células Inflamatórias e Neoplásicas, Departamento de Biologia Celular, SCB, Universidade Federal do Paraná, Curitiba, PR, Brasil.
J Infect. 2006 Jun;52(6):420-32. doi: 10.1016/j.jinf.2005.08.017. Epub 2006 Jan 4.
Macrophages play a significant role in the host defence mechanism. When activated they can produce reactive oxygen species (ROS) as well as related reactive nitrogen species (RNS). ROS are produced via NAD(P)H oxidase which catalyzes superoxide (O2-) formation. It is subsequently converted to hydrogen peroxide (H2O2) by either spontaneous or enzyme-mediated dismutation. Nitric oxide synthase (NOS) catalyzes nitric oxide (NO) formation. Canova (CA) is a Brazilian medication produced with homeopathic techniques, composed of Aconitum, Thuya, Bryonia, Arsenicum, Lachesis in distilled water containing less than 1% ethanol. Previous studies demonstrated that CA is neither toxic nor mutagenic and activates macrophages decreasing the tumor necrosis factor-alpha (TNFalpha) production. In this assay we showed that macrophages triggered with Canova increased NAD(P)H oxidase activity as well as that of iNOS, consequently producing ROS and NO respectively. Cytochrome oxidase and peroxisomes activities were inhibited by NO. As NO and O2- are being produced at the same time, formation of peroxynitrite (ONOO-) may be occurring. A potential explanation is provided on how treatment with Canova may enhance immune functions which could be particularly important in the cytotoxic actions of macrophages. CA can be considered as a new adjuvant therapeutic approach to known therapies.
巨噬细胞在宿主防御机制中发挥着重要作用。激活后,它们可以产生活性氧(ROS)以及相关的活性氮(RNS)。ROS通过催化超氧化物(O2-)形成的NAD(P)H氧化酶产生。随后,它通过自发或酶介导的歧化反应转化为过氧化氢(H2O2)。一氧化氮合酶(NOS)催化一氧化氮(NO)的形成。卡诺瓦(CA)是一种采用顺势疗法技术生产的巴西药物,由乌头、金缕梅、泻根、砷、蝰蛇毒等成分在含乙醇量低于1%的蒸馏水中制成。先前的研究表明,CA既无毒性也无致突变性,且能激活巨噬细胞,减少肿瘤坏死因子-α(TNFα)的产生。在本试验中,我们发现用卡诺瓦刺激的巨噬细胞会增加NAD(P)H氧化酶活性以及诱导型一氧化氮合酶(iNOS)的活性,从而分别产生活性氧和一氧化氮。细胞色素氧化酶和过氧化物酶的活性受到一氧化氮的抑制。由于一氧化氮和超氧阴离子同时产生,可能会形成过氧亚硝酸根(ONOO-)。关于卡诺瓦治疗如何增强免疫功能提供了一种潜在解释,这在巨噬细胞的细胞毒性作用中可能尤为重要。CA可被视为已知疗法的一种新的辅助治疗方法。