Role of nitric oxide and oxidative stress in pathophysiology of liver injury in streptozotocin-induced type 1 diabetic rats

Abstract

Type 1 diabetes mellitus (T1DM) is a severe chronic metabolic disorder characterized by hyperglycaemia because of the alterations in insulin secretion or its action. It is previously shown that hyperglycemia related oxidative stress (OS) and excessive nitric oxide (NO) production may cause severe complications in kidney and brain. In this report, it is aimed to investigate the cytotoxic effects of NO and to evaluate possible interaction with T1DM related hepatopathology. Expression levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), Cu/Zn superoxide dismutase (SOD1) and glutathione reductase (GR) were examined by immunohistochemistry in liver tissues. Results of the study revealed that levels of 8-OHdG (P<0.001), eNOS (P<0.001), eNOS (P<0.001), SOD1 (P<0.001) and GR (P<0.001) were remarkably higher in liver with T1DM than control. The most prominent finding of this study is the increased levels of 8-OHdG in the mostly hepatocyte cytoplasm. These results suggest an involvement of oxidative DNA damage and OS might play a pivotal role on hepatic degeneration and this is a novel insight of pathogenesis on the explanation of cellular processes in streptozotocin (STZ)-induced type 1 diabetic rats'liver. Furthermore, these results also suggested that STZ-induced hepatic pathology might have been augmented by the contribution of high NO expression mediated OS. Taken together, the results suggest NO related hepatic inflammation and degeneration closely implicated in pathophysiology of T1DM. The results also clearly indicated that OS plays an important role on hepatic pathology and OS biomarkers might indicate the progress of the T1DM.