Increase in antioxidant activity in procainamide-treated rats.

Recent studies suggest that in vivo procainamide oxidation underlies induction of autoimmunity by this drug. Since drug metabolism may be accompanied by generation of reactive oxygen species, plasma and liver thiobarbituric acid reacting substances (TBARS), activity of erythrocyte and liver superoxide dismutase, catalase, selenium-dependent glutathione peroxidase (Se-GPX), and plasma antioxidant activity in procainamide treated rats were evaluated. Procainamide administration increased liver lipid peroxide levels, intensified the activity of liver catalase and erythrocyte superoxide dismutase, as well as plasma antioxidant activity. The remaining biochemical parameters in the treated rats were within control values, except for the decreased erythrocyte catalase activity. We conclude, that the increased activity of free radicals observed in the treated rats could contribute to the development of procainamide induced side effects.

Modulation of procainamide toxicity by selenium-enriched yeast in rats.

Free radical processes are proposed to play a crucial role in the development of procainamide adverse effects. Therefore, selenium, as a potent antioxidant, may modified procainamide toxicity. To test this hypothesis plasma and liver thiobarbituric acid-reacting substances (TBARS), plasma antioxidant activity (AOA), erythrocyte and liver superoxide dismutase (SOD), catalase, as well as selenium-dependent glutathione peroxidase (Se-GPX) were determined in the following four groups of rats: selenium-treated (Se), procainamide-treated (P), procainamide and selenium-treated (P + Se), and control (C). Morphological studies of leukocytes [tested for lupus erythematosus (LE) cells] and liver were also made. Atypical, i.e. enlarged and swollen, leukocytes resulting from procainamide and selenium treatment were observed. These changes were found in four out of five rats in the Se group, eight out of ten in the P group, and in seven out of ten in the P + Se group. LE-like cells were observed in two rats in the P + Se group. A statistically significant decrease in plasma and liver TBARS by 20% and 36%, respectively, increased activity of SOD by 20%, catalase by 48% and Se-GPX by 15% in erythrocytes, and decreased activity of liver SOD by 17% and catalase by 22% were found in the P + Se group as compared to the P group. These results indicated that selenium exerted antioxidant effects on the procainamide-treated rats. However, selenium did not prevent the development of disturbances in leukocyte morphology, on the contrary, it possibly promoted the conversion of leukocytes to LE cells.

Effect of hemodialysis on lipid peroxidation and antioxidant system in patients with chronic renal failure.

Plasma lipid peroxidation, activity of erythrocyte superoxide dismutase (SOD) and catalase, and serum antioxidant activity (AOA) in uremic patients were examined before and after hemodialysis. An increased level of lipid peroxidation, a decreased serum AOA level, and elevated SOD and normal catalase activity before hemodialysis were observed in uremic patients compared with controls. Hemodialysis was found to produce increased lipid peroxidation, a simultaneous decrease of SOD activity, and lack of any changes in serum AOA and erythrocyte catalase. It is suggested that intensification of lipid peroxidation during hemodialysis could account for accelerated progress of atherosclerosis in patients with renal insufficiency.

Myocardial lipid peroxidation in rats treated chronically with hydralazine and its amelioration by vitamin A.

The effect of long-term intake of hydralazine on myocardial lipid peroxidation (measured as formation of thiobarbituric acid-reactive substances and lipid peroxide concentrations), superoxide dismutase activity, and the protective action of vitamin A were studied in rats. Hydralazine was administered to rats for 6 months. Compared with the controls, the left ventricle of the hydralazine-treated animals had an increased thiobarbituric-acid reactive substance content and lipid hydroperoxide concentrations per g of wet tissue. Simultaneous administration of vitamin A prevented the changes in lipid peroxidation and significantly increased the superoxide dismutase activity compared with that in hydralazine-treated rats. The results seem to indicate that the increase of lipid peroxidation in rats treated with hydralazine is due not only to the stimulation, but also to the inhibition of superoxide dismutase activity.

[Retinol level, superoxide dismutase activity and the degree of lipid peroxidation in rats with drug-induced collagenosis]. / Poziom retinolu i aktywnosc dysmutazy ponadtlenkowej a nasilenie peroksydacji lipidów u szczurów w przebiegu polekowej kolagenozy.

The retinol effect on symptoms of late toxicity of hydralazine in rats of Wistar strain during induction of the collagenosis-like syndrome has been studied. Studies have been performed during 360 days, and examination were done in three months lasting intervals. Animals were divided into 3 groups: the first was treated with hydralazine, the second with hydralazine plus retinol, and the third corresponded to the control group. It has been stated that the long-term administration of hydralazine caused the lowering of the retinol level in the serum and liver progressing according to the time of the drug use. The mean lowering of the retinol concentration for animals of the first group was 20.7% in the serum and 24.7% in the liver. Analogous results in the second group were 12.1% and 14.7%, respectively. Simultaneously activity of superoxide dismutase measured in the kidney and heart muscle homogenates was significantly lowered in animals receiving hydralazine solely. Retinol administered together with hydralazine caused an increase in the enzyme activity (about 30%) when compare with animals treated only with hydralazine. The lowering of the retinol level and of dismutase activity caused beneficial conditions for increased lipid peroxidation measured by an increase in the malonic aldehyde concentration. The concentration of malonic dialdehyde in kidneys of rats treated solely with hydralazine increased about twofold, and in the heart muscle about 3.5-fold. The supplementation of the diet with retinol in rats treated solely with hydralazine partially limited effects of enhanced free radical activity reflected in increased lipid peroxidation.