Quantification of total glutathione revealed significant decreases in the group exposed to intermittent hypoxia
compared to SIH, demonstrating a reduced hepatic antioxidant defence in these animals. The increase in TBARS and decrease in endogenous antioxidants observed in the present study further promotes oxidative stress, contributing to aggravation of the liver tissue injury. This kind of pathological synergy is evidenced in experimental models of liver damage induced by xenobiotic selleck products agents that cause oxidative stress such as carbon tetrachloride and toluene [49, 50, 52, 54, 58], by surgical procedures such as ligation of the common bile duct [51, 53] or by thymoquinone [59]. selleckchem The increased nitric oxide metabolites nitrite and nitrate in the livers of IH-35 mice confirms findings by other authors, who demonstrated a significant increase of nitric oxide in animals exposed to IH simulating OSA (6 min/6 min) during 120 days [48], and to hypobaric hypoxia during 32 days [60]. The increase of NO, along with increased free radicals,
may generate nitrosative stress caused by the reaction products of these two substances, such as peroxide nitrite (OONO•) formed by the reaction between NO and O2 -• [11]. Much evidence indicates that oxidative and nitrosative stress have important roles in the complication of hypoxia [61]. OSA is usually accompanied by arterial hypertension, pulmonary hypertension, myocardial infarction and
stroke, which may be due to changes in nitric oxide production [62]. Veasey et al. had demonstrated irreversible basal forebrain nitrosative damage as a possible cause for residual sleepiness in OSA [63]. It is increasingly clear that IH is capable of causing liver tissue damage. This was here demonstrated by several lines of evidence: elevated circulating levels of liver enzymes, NO increase, damage to lipids and DNA, and reduced endogenous antioxidant defences. Further translational research is necessary to completely correlate these findings with the NASH pathology. Conclusions The present results suggest that a model of intermittent Phospholipase D1 hypoxia for 35 days, simulating sleep apnoea, is useful to investigate liver injury by oxidative and nitrosative stress. Exposure to intermittent hypoxia during 21 days may be insufficient to produce hepatic damage. Acknowledgements This research was supported by the Research Incentive Fund of the Hospital de Clínicas de Porto Alegre (HCPA-FIPE), the Coordination of Improvement of Higher Education Personnel (CAPES), the National Council of Scientific and Technological Development (CNPq) and the GSK1904529A price Lutheran University of Brazil (ULBRA). References 1. Dempsey JA, Veasey SC, Morgan BJ, O’Donnell CP: Pathophysiology of sleep apnea. Physiol Rev 2010, 90:47–112.PubMedCrossRef 2.