Effect of chronic hypoxia on glutathione status and membrane integrity in the pancreas

Background: Our recent study has shown that chronic hypoxia could upregulate significantly a local renin-angiotensin system in the pancreas. The activation of such a local renin-angiotensin system may provide an alternate mechanism that leads to the generation of reactive radical species in the pancreas during chronically hypoxic exposure. The present study aims at elucidating the antioxidant status in the pancreas during varying degrees of chronic hypoxia. Methods: Sprague-Dawley rats were exposed to an isobaric hypoxic (10% oxygen) chamber for a period up to 28 days. The glutathione status and membrane integrity of the pancreas were studied with a time course of chronic hypoxia (3, 7, 14, 21 and 28 days). The effect of chronic hypoxia on changes of oxidative states in the pancreas was assessed based on the measurements of glutathione, malondialdehyde, α-amy-lase and DNA fragmentation using biochemical assays. Results: Pancreatic glutathione was decreased drastically after 3-day hypoxia and its level was almost completely recovered after 7-day hypoxia. Malondialdehyde was not affected while DNA fragmentation was increased significantly in a time-dependent manner during the course of chronic hypoxia. Membrane integrity of the pancreatic cells was improved, as evidenced by the decrease of plasma a-amylase during the time-course study of chronic hypoxia. Conclusion: Pancreatic glutathione was depleted only in the early period of chronic hypoxia followed by a rapid recovery, suggesting that adaptive response of the pancreas may occur during chronic hypoxia. The enhancement of glutathione-dependent antioxidant capacity during chronic hypoxia prevented oxidative damage to the membrane of the pancreatic cells.