Antioxidant enzyme alterations in experimental and clinical diabetes

Abstract

Previous studies from our laboratory have demonstrated the presence of complex alterations in the activities of antioxidant enzymes in various tissues of rats with streptozotocin (STZ)-induced diabetes. In the present investigation, it is shown that rats made diabetic with alloxan (ALX), an agent differing from STZ both chemically and in its mechanism of diabetogenesis, show virtually identical tissue antioxidant enzyme changes which, as is the case with STZ, are preventable by insulin treatment. The finding that the patterns of antioxidant enzyme alterations in chemically-induced diabetes are independent of the diabetogenic agent used and the presence of similar abnormalities in tissues of spontaneously diabetic (BB) Wistar rats (particularly when diabetic control is less than optimal) suggest that the changes observed are a characteristic feature of the uncontrolled diabetic state and that these may be responsible for (or predispose to) the development of secondary complications in clinical diabetes. Comparative studies involving red cells of diabetic rats and human diabetics revealed a number of common changes, namely an increase in glutathione reductase activity, a decreased susceptibility to oxidative glutathione depletion (which was related to the presence of hyperglycemia) and an increased production of malondialdehyde (an indirect index of lipid peroxidation) in response to in vitro challenge with hydrogen peroxide. In the diabetic patients, the extent of this increase in susceptibility of red cell lipids to oxidation paralleled the severity of diabetic complications. Our results suggest that increased (or uncontrolled) oxidative activity may play an important role in the pathogenesis of complications associated with the chronic diabetic state.

High dose propofol enhances red cell antioxidant capacity during CPB in humans

“…This is important because the myocardium is vulnerable to oxidative injury due to low levels of antioxidant enzymes found in these tissues. 2s, 26 Our intention is to substantiate this finding with expanded study ofpropofol's antioxidant potential during ACBP. This study was designed to find the appropriate dose of propofol to enhance red cell antioxidant status, not to find the appropriate dose for optimal hemodynamic stability.…”

Lipid Peroxidation in the Pancreas and Other Organs in Streptozotocin Diabetic Rats

“…Diabetes mellitus should be associated with increased oxidative stress because blood concentrations of lipid peroxides increase in experimental and clinical diabetes (1,2). Oxidative stress means the production of highly reactive oxygen radicals that are toxic to the cells, par ticularly to the cell membrane in which these radicals interact with the lipid bilayer and produce lipid peroxides (3).…”

Modulation of Antioxidant Enzyme Expression and Activity by Paraquat in Renal Epithelial NRK-52E Cells

“…For instance, a significant increase in GSH-Px (Godin et al, 1988;Kakkar et al,1995;Duncan et al,1996;Ray et al, 2007), CAT (Matkovics et al, 1982;Yadav et al,1997;Ray et al, 2007), and SOD activity (Garcia-Alfonso et al, 1995;Ray et al, 2007) and decrease in GSH-Px (Senator et al, 2004;Sindhu et al, 2005), CAT (Kakkar et al,1995, Sommerburg et al, 2002 and SOD activity (Kakkar et al, 1995;Senator et al, 2004) has been noted during oxidative stress injury depending on the experimental conditions. However, in the current study, paraquat significantly reduced the activity and expression of SOD, the activity of CAT with no significant change in CAT expression.…”

“…For example, under diabetic conditions in which oxidative stress plays an important role in the development of complications involving oxidant injury (Maiese et al, 2007;Kaneto et al, 2007), SOD activity has been shown to be reduced (Godin et al, 1988) or unaffected , CAT activity increased (Matkovics et al, 1982;Yadav et al,1997) or unaffected (Kakkar et al,1995) and GSH-Px activity increased (Godin et al, 1988;Kakkar et al, 1995;Duncan et al, 1996) or decreased (Tagami et al, 1992;Van den Branden et al, 2000). Antioxidant enzyme activities are also altered in chronic renal failure (CRF) in which oxidative stress also plays an important part (Modlinger et al, 2004), however, as with diabetic conditions, the true effects are still unclear.…”