Simulating Sleep Apnea by Exposure to Intermittent Hypoxia Induces Inflammation in the Lung and Liver

Abstract

Sleep apnea is a breathing disorder that results from momentary and cyclic collapse of the upper airway, leading to intermittent hypoxia (IH). IH can lead to the formation of free radicals that increase oxidative stress, and this mechanism may explain the association between central sleep apnea and nonalcoholic steatohepatitis. We assessed the level of inflammation in the lung and liver tissue from animals subjected to intermittent hypoxia and simulated sleep apnea. A total of 12 C57BL/6 mice were divided into two groups and then exposed to IH (n = 6) or a simulated IH (SIH) (n = 6) for 35 days. We observed an increase in oxidative damage and other changes to endogenous antioxidant enzymes in mice exposed to IH. Specifically, the expression of multiple transcription factors, including hypoxia inducible factor (HIF-1α), nuclear factor kappa B (NF-κB), and tumor necrosis factor (TNF-α), inducible NO synthase (iNOS), vascular endothelial growth factor (VEGF), and cleaved caspase 3 were shown to be increased in the IH group. Overall, we found that exposure to intermittent hypoxia for 35 days by simulating sleep apnea leads to oxidative stress, inflammation, and increased activity of caspase 3 in the liver and lung.

Hepatocyte Hypoxia Inducible Factor-1 Mediates the Development of Liver Fibrosis in a Mouse Model of Nonalcoholic Fatty Liver Disease

“…Second, HIF-1α knockout was specific for hepatocytes, whereas other liver cell types, for example stellate cells, could still express LOX; it would suggest that the difference in fibrosis between HIF-1α hepatocyte genotypes was LOX-independent. Third, HIF-1 may also modulate hepatic inflammation, which could contribute to fibrogenesis [46, 47]. …”

Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies

“…Perhaps experimental evidence derived from sleep apnoea may shed light upon this. It is well-established that intermittent systemic hypoxia resulting from sleep apnoea is associated with systemic inflammation (da Rosa et al, 2012;Gileles-Hillel et al, 2017;Perrini et al, 2017). More importantly, intermittent systemic hypoxia may profoundly impact on metabolic homeostasis.…”

Obstructive Sleep Apnea and Kidney Disease: A Potential Bidirectional Relationship?

“…[105][106][107][108][109] Markers of cellular oxidative stress include malondialdehyde (a lipid peroxidation end product), F2-isoprostanes, and lipid hydroperoxide. 108 On the other hand, sleep related breathing disorders, especially OSA, disrupt the balance between ROS removal and formation to initiate oxidative stress, [110][111] and thus constitute another indirect pathogenesis of sleep apnea-associated CKD.…”