UBC Theses and Dissertations
Renal injury in a mouse model of sleep apnea is prevented by alpha-lipoic acid through reduced oxidative stress and inflammation Abuyassin, Bisher Hassan
Epidemiological studies demonstrate an association between obstructive sleep apnea (OSA) and accelerated loss of kidney function. OSA is characterized by repetitive episodes of intermittent hypoxia (IH) during sleep, which provokes systemic and renal oxidative stress and inflammation. Here we hypothesized that IH induces structural and functional renal injury by increasing glomerular growth factors, increasing oxidative stress and inflammation, and that α-lipoic acid (LA), an antioxidant, attenuates this injury. To address this hypothesis, the ability of LA to mitigate the structural and functional aspects of renal injury secondary to IH was examined. Ten 8-week old wild-type male CB57BL/6 mice were randomly assigned to receive either IH or intermittent air (IA) for 60 days. The first study involved histological measurements of glomerular area and mesangial matrix expansion (MME), where glomerular growth factors were quantified by immunohistochemistry. Renal cellular apoptosis was investigated by measuring apoptotic proteins in kidney cortex. Finally, measurements of renal function were made by measuring serum creatinine and 24-hour urinary albumin. For the second study, 20 mice were randomized to receive either IH or IA, with regular diet (RD) or 0.2% w/w LA-enriched diet. After 60 days, samples of urine and plasma were collected. Markers for oxidative stress, inflammation, apoptosis, and tubular injury in kidney cortex were quantified. Glomerular area and MME were measured as well. Compared to controls, IH-exposed mice had increased glomerular areas and MME, accompanied by increases in glomerular growth factors and cellular apoptosis markers. IH-exposed mice had increases in albuminuria but not in serum creatinine. The second study demonstrated reduced urinary albumin excretion in the IH-LA group compared to IH-RD. Histological assessment showed significant increases in glomerular area of IH-RD compared to IH-LA. Treatment with LA also normalized systemic and renal oxidative stress and inflammation, and attenuated renal cellular apoptosis and tubular injury secondary to IH. These findings indicate for the first time that IH causes structural and functional kidney injury and increases renal cellular apoptosis, and this injury was attenuated by the antioxidant effect of LA. Treatment with LA may be a potentially promising therapy to reduce renal dysfunction in patients with OSA.
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