ABSTRACT
Haptoglobin is a hemoglobin-binding acute-phase protein which possesses anti-inflammatory and antioxidative properties. In this study, we investigated changes in protein expression of rat haptoglobin under diabetes-related inflammatory and oxidative stress conditions induced by an i.p. injection of streptozotocin. The progress of diabetes during an 8-week follow-up period was associated with the increased presence of haptoglobin in the serum and in the liver. This increase was most prominent during the first 2 weeks after which it started to decline. Temporary changes in haptoglobin expression strongly correlated with the serum levels of TNF-α and IL-6. Lower haptoglobin expression at the fourth week and thereafter correlated with a decrease in TNF-α concentration and changes in the TNF-α/IL-6 ratio. Based on the decrease of GSH/GSSG ratio and antioxidant enzyme activities in the liver until the end of fourth week, it was concluded that the liver was exposed to oxidative stress and injury which in the presence of the above-mentioned inflammatory mediators lead to different haptoglobin expression profiles at different stages of diabetes. An inverse correlation was observed between the haptoglobin and free iron serum levels in diabetic rats. The higher levels of haptoglobin during the first 2 weeks were accompanied by a lower level of free iron. In view of the established function of haptoglobin, we discuss its possible role in decreasing oxidative stress during the early stage of diabetes.
Subject(s)
Antioxidants/metabolism , Diabetes Mellitus, Experimental/blood , Haptoglobins/metabolism , Liver/metabolism , Animals , Diabetes Mellitus, Experimental/pathology , Disease Progression , Gene Expression , Glutathione/blood , Haptoglobins/genetics , Inflammation/blood , Inflammation/pathology , Interleukin-6/blood , Iron/blood , Liver/pathology , Male , Oxidative Stress , Rats , Rats, Wistar , Streptozocin , Thiobarbituric Acid Reactive Substances/metabolism , Tumor Necrosis Factor-alpha/bloodABSTRACT
PURPOSE: The aim of this study was to investigate whether the daily administration of α-lipoic acid (LA) during 4 weeks prevents the redox disturbance in red blood cells (RBC) described in diabetes METHODS: Multiple low-dose streptozotocin (STZ) diabetes was induced in rats by the administration of 40 mg/kg STZ intraperitoneally (i.p.) for 5 consecutive days. LA was applied at a dose of 10 mg/kg i.p. for 4 weeks, starting from the last day of STZ administration. RESULTS: The LA-treated diabetic rats exhibited a general systemic improvement, revealed as the near restoration of body weight and of essential biochemical parameters. The latter was displayed as decreased hyperglycemia, lower triglyceride levels and lower serum activities of alanine aminotransferases and aspartate aminotransferases that point to a general improvement of diabetes-linked organ "lesions". The LA-treated diabetic rats also exhibited significant alleviation of oxidative stress, manifested as decreased lipid peroxidation and lower glycation levels of serum proteins and hemoglobin, while the RBC exhibited increased activities of antioxidant enzymes and elevated levels of reduced glutathione. In RBC, this was accompanied by decreased post-translational glycosylation by O-bound ß-N-acetylglucosamine (O-GlcNAc) of the antioxidant enzymes superoxide dismutase and catalase and of heat shock proteins HSP70 and HSP90. CONCLUSION: LA through its powerful antioxidant activity preserves the structural and functional integrity of RBC in diabetes. The RBC can then assume a more efficient role as the first line of systemic defense against diabetic complications arising from oxidative stress-induced damage of other tissues and organs.
