Two selleck compound mechanisms are proposed for the morbidity caused by OSA: the activation of inflammatory factors and oxidative stress [42, 43], which also can be modulated by genetic, lifestyle and environmental LY2606368 factors [43, 44]. Oxidative stress plays an important role in various diseases as well as in OSA, which causes an effect similar to ischemia-reperfusion [18] in which there is activation of xanthine oxidase, leading to the formation free radicals and further imbalance between oxidants and antioxidants [4–6]. The analysis of liver integrity showed that the liver tissue of mice subjected to intermittent hypoxia was damaged, but only after 35 days, as demonstrated by the significant increase in circulating
AST, ALT and alkaline phosphatase. The present results demonstrate damage both at cytoplasmic and mitochondrial level, confirmed by the presence in the histological examination of ballooning, steatosis, necrosis and the presence of neutrophils in the liver, similar to what is observed in NASH [45]. In the evaluation
of hepatic lipid peroxidation, Niraparib clinical trial we observed a significant increase in lipid oxidative damage in animals that were subjected to hypoxia for 35 days, as indicated by the TBARS test, but not in group IH-21. This damage can be caused by the increase of free radicals in the liver tissue. Similar data have been reported in other studies of intermittent hypoxia [46–48] and by our laboratory in other experimental models of hepatic oxidative damage [49–54]. As we did not observe liver damage in animals exposed to IH for 21 days, by the liver enzyme, histological, or lipid peroxidation assays, we concluded that this duration of IH causes
no damage to the organ. Therefore, dosages of antioxidant enzymes, comet assay and Low-density-lipoprotein receptor kinase nitrites metabolites were not conducted in the IH 21 group. Comet assay in liver tissue revealed a significant increase in DNA damage in the IH-35 group in comparison to the SIH group. No evidence of damage was observed in blood tissue. The rate of DNA damage detected by the comet assay depends on the tissue or organ analyzed [55]. Here, the DNA damage was observed only in the tissue most susceptible to lesions produced by IH. In the alkaline version used, the comet assay detects a broad spectrum of DNA lesions, including single strand breaks [56, 57]. Previous comet assay and TBARS data have demonstrated increased formation of free radicals in sleep apnoea patients [11]. Possibly, the formation of superoxide radical (O2 -•) and hydrogen peroxide (H2O2), which appear to be increased in individuals with OSA, is due to the conversion of xanthine dehydrogenase (type D) into its oxidase (type O) form in hypoxia, followed by the activation of the oxidase form during reoxygenation (normoxia) by the hypoxanthine formed during hypoxia. This xanthine oxidase activity generates O2 -•, H2O2, and uric acid [4, 11].