The effect of oxidants on biomembranes and cellular metabolism.
During the reductive process in the tissues, the aerobes generate a number of oxidants. Unless these oxidants are reduced, oxidative damage and cell death would occur. Oxidation of plasma membrane lipids leads to autocatalytic chain reactions which eventually alter the permeability of the cell. The role of oxidative damage in the pathophysiology of diabetic complications and ischemic reperfusion injury of myocardium, especially the changes in the channel activity which may lead to arrhythmia have been studied. Hyperglycemia activates aldose reductase which could efficiently reduce glucose to sorbitol in the presence of NADPH. Since NADPH is also aldose required by glutathione reductase for reducing oxidants, its diversion would lead to membrane lipid oxidation and permeability changes which are probably responsible for diabetic complications such as cataractogenesis, retinopathy, neuropathy etc. Antioxidants such as butylated hydroxy toluene (BHT) and also reductase inhibitors prevent or delay some of these complications. By using patch-clamp technique in isolated frog myocytes, we have shown that hydroxy radicals generated by ferrous sulfate and ascorbate as well as lipid peroxides such as t-butyl hydroperoxide facilitate the entry of Na+ by oxidizing Na+-channels. Increased intracellular Na+ leads to an increase in Na+/Ca2+ exchange. The increased Na+ concentration by itself may produce electrical disturbance which would result in arrhythmia. Increased Ca2+ may affect proteases and may help in the conversion of xanthine dehydrogenase to xanthine oxidase, consequently increased production of super oxide radicals. Increased membrane lipid peroxidation and other oxygen free-radical associated membrane damage in myocytes has been demonstrated.
Srivastava
S K
SK
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Ansari
N H
NH
Liu
S
S
Izban
A
A
Das
B
B
Szabo
G
G
Bhatnagar
A
A
D000449:Aldehyde Reductase / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D008954:Models, Biological; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism; D010084:Oxidation-Reduction; D013401:Sugar Alcohol Dehydrogenases / Q000502:physiology*
D005609:Free Radicals; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase