Abstract
Problem statement: Involvement of oxidative stress in the pathogenesis of diabetic complications has been proposed. 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a new sensitive biomarker of the oxidative DNA damage in vivo. Apoptosis via Fas/Fas Ligand (FasL) interactions has been proposed to be a major T-cell-mediated effector mechanism in autoimmune diabetes. This study was undertaken to investigate whether the serum levels of 8-OHdG and circulating soluble Fas/Fas Ligand, two transmembrane glycoproteins involved in apoptosis, are altered in patients with type 2 diabetes. Approach: 8-OHdG, sFas and sFasL were measured with the ELISA method in twenty normal controls (group I), thirty patients with type 2 DM (duration ranged from 1-3 years, group II) and in thirty patients with type 2 DM (duration ranged from 5-10 years, group III). Also, serum glucose (Fasting and postprandial), HbA1c, insulin, lipid profile (total cholesterol, triacylglycerol, HDL-c and LDL-c) and serum malondialdehyde (MDA) level were determined. Results: The patients with a long duration of diabetes were poorly controlled and had significantly higher levels of HbA1c (p<0.05) when compared to control group. Serum levels of total cholesterol, triacylglycerol and LDL-c were significantly higher (p<0.05) in diabetic patients in comparison with healthy normal control, while HDL-c level was significantly lower in both groups than in the control group (p<0.05). 8-OHdG and MDA levels were significantly higher in both diabetic groups than in the control group. sFas serum levels were significantly increased in both diabetic groups as compared with normal controls (10.5±3.2, 14.4±3.4 ng mL-1 Vs 4.5±2.1 ng mL-1, p<0.05), but the levels were significantly higher in patients with long duration of diabetes when compared with that of short duration of diabetes (p<0.05). sFasL serum levels were less than 0.1 ng mL-1 in normal control group and the same results were observed in sera from groups of diabetic patients. A significant positive correlation was observed between 8-OHdG and each of HbA1c, MDA, HOMA index and sFas in diabetic group of long duration. On the other hand, there was a positive correlation between sFas levels and each of HbA1c, MDA and HOMA index. Also MDA was positively correlated with HbA1c and HOMA index. HbA1c was positively correlated with HOMA index. Conclusion: In type 2 diabetic patients, 8-OHdG could be a sensitive biomarker for evaluating oxidative DNA damage, there seems to be a dysregulation of apoptosis, as expressed by enhanced sFas levels, suggesting that these markers may be helpful for the early diagnosis of type 2 diabetic patients.
Highlights
Diabetes mellitus is characterized by increased production of Reactive Oxygen Species (ROS), sharp reduction in antioxidant defense and altered cellular redox status
The aim of this study was designed to evaluate the oxidative DNA damage (8-hydroxydeoxyguanosine), in addition to elucidate the changes of Fas/Fas ligand levels to perdict the early diagnosis of type 2 diabetic patients
III: Type 2 diabetic patients with duration ranged from 5-10 years
Summary
Diabetes mellitus is characterized by increased production of Reactive Oxygen Species (ROS), sharp reduction in antioxidant defense and altered cellular redox status. Hyperglycemia, a key clinical manifestation of diabetes mellitus, generates more reactive oxygen species, and attenuates antioxidative mechanisms by scavenging enzymes and substances (Zhang et al, 2011). A potentially harmful imbalance between the level of pro-oxidants and anti-oxidants. It can cause cellular injury and tissue damage by promoting several reactions e.g., lipid perxidation, Corresponding Author: Mohamed H.
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