Hepatic oxidative stress in an animal model of sleep apnoea: effects of different duration of exposure

We investigated hepatic oxidative stress in adult mice subjected to intermittent hypoxia, simulating sleep apnoea. Three groups were submitted to 21 days of IH (IH-21), 35 days of IH (IH-35), or 35 days of sham IH. We assessed the oxidative damage to lipids by TBARS and to DNA by comet assay; hepatic tissue inflammation was assessed in HE-stained slides. Antioxidants were gauged by catalase, superoxide dismutase, glutathione peroxidase activity and by total glutathione.After IH-21, no significant change was observed in hepatic oxidative stress. After IH-35, significant oxidative stress, lipid peroxidation, DNA damage and reduction of endogenous antioxidants were detected.In an animal model of sleep apnoea, intermittent hypoxia causes liver damage due to oxidative stress after 35 days, but not after 21 days.In obstructive sleep apnoea (OSA), pharyngeal occlusion occurs, typically for 10 to 40 seconds, causing a decrease of PaO2 and an increase in PaCO2, ending with an arousal [1]. Intermittent hypoxia due to OSA causes oxidative stress, a recognized mechanism in the nonalcoholic fatty liver disease (NAFLD), which may progress to nonalcoholic steatohepatitis (NASH) [2].Intermittent hypoxia (IH) increases liver damage [3]. During hypoxia, activation of xanthine oxidase [4], NAPDH oxidase [5], and phospholipase A2 [6] occurs, forming reactive oxygen species (ROS). Increased ROS and decreased antioxidant capacity [7-9] induce oxidative stress [10]. In hypoxia, superoxide anions are formed, which, together with nitric oxide (NO), the main vasodilator, produce peroxynitrite [11-13]. This reaction reduces the bioavailability of NO, attenuating NO-dependent vasodilation, capillary perfusion and expression of adhesion molecules [14-17].The formation of ROS in OSA is similar to what occurs in ischemia-reperfusion [18]. Oxidative stress leads to inflammation, recognised as a mechanism of the pathophysiology of OSA [19]. Excessive formation of ROS leads to lipid peroxidation in