Tanaka R
Department of Pharmacology, Akita University School of Medicine, Japan.
J Toxicol Sci. 1995 Sep;20(4):401-6. doi: 10.2131/jts.20.4_401.
Active oxygens cause major tissue damages in a number of distress syndromes. Pentoxifyline (POF) and its metabolites, a methylxanthine derivative, are inhibitors of superoxide anion production in stimulated human leukocytes. Examination was made of the effects of POF on the genotoxic actions of active oxygens. The frequency of sister-chromatid exchanges (SCEs) induced by paraquat (PQ), a generator of superoxide anions was significantly reduced in cultured Chinese hamster lung cells (CHL/IU) pretreated with POF. POF metabolite samples were also effective. Superoxide anion scavenging effect of POF were found at 0.1 mM, and it was more potent than that of POF metabolite samples. POF and its metabolite sample inhibited xanthine oxidase (XOD) at 1 mM but not at 0.1 mM. POF would thus appear to protect cells from the toxic effects of active oxygens on chromosomes and tissue damage by not only inhibition of active oxygen production in leukocytes but also by scavenging activity of active oxygens.
活性氧在多种应激综合征中会导致严重的组织损伤。己酮可可碱(POF)及其代谢产物,一种甲基黄嘌呤衍生物,是受刺激的人白细胞中超氧阴离子产生的抑制剂。研究了POF对活性氧遗传毒性作用的影响。在用POF预处理的培养中国仓鼠肺细胞(CHL/IU)中,由超氧阴离子生成剂百草枯(PQ)诱导的姐妹染色单体交换(SCE)频率显著降低。POF代谢物样品也有效。在0.1 mM时发现POF具有超氧阴离子清除作用,且其作用比POF代谢物样品更强。POF及其代谢物样品在1 mM时抑制黄嘌呤氧化酶(XOD),但在0.1 mM时无此作用。因此,POF似乎不仅通过抑制白细胞中的活性氧产生,还通过活性氧清除活性来保护细胞免受活性氧对染色体的毒性作用和组织损伤。