Effects of Ozone Oxidative Preconditioning on TNF-α Release and Antioxidant-Prooxidant Intracellular Balance in Mice During Endotoxic Shock

摘要

Ozone oxidative preconditioning is a prophylactic approach, whichfavors the antioxidant-prooxidant balance for preservation ofcell redox state by the increase of antioxidant endogenous systemsin both in vivo and in vitro experimental models. Our aim is toanalyze the effect of ozone oxidative preconditioning on serumTNF-α levels and as a modulator of oxidative stress onhepatic tissue in endotoxic shock model (mice treated withlipopolysaccharide (LPS)). Ozone/oxygen gaseous mixture which wasadministered intraperitoneally (0.2, 0.4, and 1.2 mg/kg)once daily for five days before LPS (0.1 mg/kg,intraperitoneal). TNF-α was measured by cytotoxicity onL-929 cells. Biochemical parameters such as thiobarbituric acidreactive substances (TBARS), enzymatic activity of catalase,glutathione peroxidase, and glutathione-S transferase weremeasured in hepatic tissue. One hour after LPS injection therewas a significant increase in TNF-α levels in mouse serum.Ozone/oxygen gaseous mixture reduced serum TNF-α levels ina dose-dependent manner. Statistically significant decreases inTNF-α levels after LPS injection were observed in micepretreated with ozone intraperitoneal applications at 0.2(78%), 0.4 (98%), and 1.2 (99%). Also a significantincrease in TBARS content was observed in the hepatic tissue ofLPS-treated mice, whereas enzymatic activity of glutathion-Stransferase and glutathione peroxidase was decreased. However inozone-treated animals a significant decrease in TBARS content wasappreciated as well as an increase in the activity of antioxidantenzymes. These results indicate that ozone oxidativepreconditioning exerts inhibitory effects on TNF-αproduction and on the other hand it exerts influence on theantioxidant-prooxidant balance for preservation of cell redoxstate by the increase of endogenous antioxidant systems.