<原著>エンドトキシン投与時の生化学的研究 : 過酸化脂質の産生機序とこれに及ぼす抗酸化剤の効果を中心として

Abstract

In recent years, lipid peroxide formation in various diseases or abnormal states and its notorious effects to many tissues are well known. We examined the lipid peroxide formation and changes of activities of free radical scavengers-SOD, GSH-px-in rat tissue following administration of E. coli endotoxin (ETX). And the effects of pre-treatment of free radical scavengers-GSH, α-tocopherol, SOD, -and glucocorticoid on lipid peroxide level in tissues, mortarity and lung weight/body weight ratio (L/B) in endotoxin shock rats were tested. The results were as follows. 1) The tissue (lung & liver) levels of lipid peroxide (TBARS value) showed a remarkable increase within 24hours after administration of ETX. The repeated administration of small dose of ETX, which did not deteriorate hemodynamic state in rat, also gave rise to an increase of tissue level of TBARS. 2) The increase of tissue level of TBARS correrated inversely with decrease of SOD activity not in liver tissue but in pulmonary tissue. 3) Inhibitory effect of pre-treated free radical scavengers on increase of TBARS in tissues and of L/B ratio following endotoxicosis were detected. In these effects of extrinsic free radical scavengers, the effect of GSH was most prominent and followed by that fo α-toco. and SOD. 4) L/B ratio, as an index of pulmonary edema, was well correlated with the increase of lung TBARS. 5) Glucocorticoid pre-treatment protected rats from tissue damage induced by ETX shock. These results suggested that in endotoxicosis, shock state or not, tissue damage was augumented by lipid peroxide formation. In shock state, one of the causes of increase of tissue TBARS was an increase in production of lipid peroxide due to tissue hypoxia. And the decrease of degradation of formed lipid peroxide due to lowering of tissue SOD activity as showed in lung tissue was another cause. However, from the findings that one of the pathological changes of endotoxicosis is neutrophil sequestration in pulmonary capillary beds and these sequestrated neutrophils release active oxygen to outer medium, we speculated that, not only in shock state but also in small dose administration of ETX, the tissue increase of TBARS may be in some degree mediated by these active oxygen from these sequestrated neutrophils. The effectiveness of glucocorticoid pre-treatment in results may be partly due to inhibition of this neutrophil sequestration in capillary beds. As conclusion, we thought that free radical scavengers-especially GSH-and large dose of glucocorticoid administration are effective against ETX-induced tissue damage by decrease of tissue lipid peroxide formation.