Red Blood Cell Membrane Lipid Research Articles

Lipid Peroxidative Potency of Photosensitized Thiazide Diuretics

We examined the lipid peroxidative potency and photohemolytic activity of thiazide diuretics, especially penflutizide (PFZ), to determine the molecular mechanism of thiazide phototoxicity. Ultraviolet A irradiation of squalene in the presence of PFZ, hydrochlorothiazide, methiclothiazide, benzylhydrochlorothiazide, or trichlormethiazide induced in vitro peroxidation as measured by production of the hydroperoxides and thiobarbituric acid-reactive substances. Among the thiazides, PFZ showed the highest potency to photooxidize lipids. PFZ-photosensitized peroxidation of squalene was repressed by the presence of sodium azide or 2,5-dimethylfuran and was accelerated in a D2O suspension. These findings suggest the participation of singlet oxygen in PFZ photoperoxidation of squalene (type II mechanism). PFZ-photosensitized lysis of red blood cells (RBC) accompanied by formation of hydroperoxides in RBC membrane lipids was also noted. These results suggest that membrane lipids can be one of the target molecules of thiazide phototoxicity.

Red blood cell membrane lipid peroxidation in continuous ambulatory peritoneal dialysis patients.

We have recently described that in the erythrocytes from uremic patients on chronic hemodialysis, the pentose-phosphate shunt is defective, the membrane concentrations of malonyldialdehyde, resulting from peroxidation of polyunsaturated fatty acids in the membranes themselves, are increased, and the concentrations of vitamin E, an antioxidizing agent, are reduced. In the present study we have analyzed these same metabolic aspects in a group of uremic patients in continuous ambulatory peritoneal dialysis. We have found normal function of the pentose-phosphate shunt, slightly elevated concentrations of malonyldialdehyde compared to controls, but definitely lower than in chronic hemodialysis patients, and higher tocopherol concentrations than in both controls and chronic hemodialysis patients.

An essential requirement for ferrous-haemoglobin in the hydrogen peroxide stimulated oxidation of red blood cell membrane lipids

An essential requirement for ferrous-haemoglobin in the hydrogen peroxide stimulated oxidation of red blood cell membrane lipids

Evidence of red blood cell membrane lipid peroxidation in haemodialysis patients.

Some metabolic alterations of the pentose-phosphate shunt can increase susceptibility to red blood cell (RBC) lipid peroxidation in uraemic patients on maintenance haemodialysis. We investigated this phenomenon in 19 uraemic patients undergoing chronic haemodialysis by determining RBC malonyldialdehyde (MDA), a secondary product of lipid peroxidation and plasma and RBC tocopherols, which are powerful antioxidants. Evidence of RBC membrane lipid peroxidation was demonstrated by an increase of RBC MDA. RBC tocopherols were significantly decreased because of enhanced antioxidant activity. No significant variations of these parameters were found before and after dialysis.

Altered lipoprotein metabolism in spontaneous vitamin E deficiency of owl monkeys

Certain owl monkeys (AOT) develop spontaneous hemolytic anemia that responds to vitamin E. The anemia is associated with red blood cell lipid peroxidation and altered red blood cell membrane lipid composition. To investigate these changes, plasma lipid and lipoprotein profiles were characterized in anemic, anemia-susceptible, and anemia-resistant AOT. The plasma vitamin E and vitamin A concentrations were assessed as an index of fat absorption and the effect of corn oil supplementation and vitamin E-selenium injection were measured. Anemia-susceptible AOT had depressed plasma levels of vitamin E and A and an altered lipoprotein metabolism characterized by elevated ratios of low/high density lipoprotein cholesterol and free to esterified cholesterol in these lipoproteins. Vitamin E-selenium injection in anemia-susceptible AOT increased the plasma vitamin E, and vitamin E and corn oil supplements reduced the high density lipoprotein free to esterified cholesterol ratio. The data suggest that the AOT suffer from fat malabsorption and that the consequences (including tocopherol deficiency) result in altered cholesterol metabolism.

On the mechanism of phenylhydrazine-induced hemolytic anemia

The thiobarbituric acid (TBA)-reactants have been measured in the circulating red blood cells (RBC) and RBC trapped in the spleens of normal and phenylhydrazine-treated rats. There was significant TBA-reactivity in the circulating RBC of phenylhydrazine-treated rats which was increased 3-fold in RBC obtained from the spleen. Since lipid peroxidation accompanies formation of TBA-reactive malonyldialdehyde, it is suggested that phenylhydrazine induces anemia as a consequence of peroxidation of RBC membrane lipids and this effect may be a result of the autoxidation of the drug and the interaction of oxygen radicals with membrane lipids.

The relationship of red cell membrane lipid content to red cell morphology and survival in patients with liver disease.

The relationship of red blood cell (RBC) membrane lipid content to RBC morphology and survival was studied in patients with liver diseases. An increase in RBC cholesterol and phospholipid was detected in most patients with hepatocellular disease or cholestatic jaundice but the alteration in RBC lipid content did not correlate with RBC survival. The main abnormality of RBC morphology observed was the presence of macrocytes and target cells. In a small proportion of patients (approximately 3%) with severe hepatocellular disease, significant numbers of severely deformed ("spur") cells were seen. In these patients haemolysis was moderately severe and the RBC lipid profile showed increased membrane cholesterol without a concomitant increase in phospholipids. It is concluded that only in patients with "spur" cell anaemia do the morphological alterations lead to premature removal of cells from the circulation. The cause of the shortened RBC survival in jaundiced patients without "spur" cells remains to be determined.