Effect of coumarins on mitochondrial function I. Uncoupling of oxidative phosphorlation.

8-Acetyl-5,7-diemthoxy-4-phenylcoumarin at concentrations 0.03 to 0.3 mM uncoupled oxidative phosphorylation, in vitro, in rat liver mitochondria. Preincubation of mitochondria with the compound enhanced this effct. Similar uncoupling was observed with 5,7-dihydroxy-4phenylcoumarin; 7-acetonyloxycoumarin; 6,7-dimethyl-4-phenylcoumarin and 4-phenyldaphentin also. All these compounds stimulated mitochondrial ATPase activity three- to eight-fold. However, coumarin, the paretn substance of all these compounds had no effect on oxidative phosphorylation in mitochondria.

Effect of vitamin E on lipid components of atherogenic rats.

Rats were made atherogenic by feeding a synthetic diet containing high fat (20%) and cholesterol (2%) for two, three or four weeks. For alpha-tocopherol acetate supplementation studies, the rats on atherogenic diet for two weeks received alpha-tocopherol acetate 5 mg or 20 mg/100 g body weight once daily, orally for two weeks along with the atherogenic diet. Atherogenic diet fed rats showed elevated plasma cholesterol, hepatic total lipids, triglycerides and cholesterol and the increase in the constituents paralleled the period of feeding the diet. Administration of alpha-tocopherol acetate lowered the plasma cholesterol and hepatic lipid components in a dose-dependent manner. Supplementation with alpha-tocopherol acetate reduced the elevated osmotic fragility of erythrocytes from atherogenic diet fed rats to that of control levels. Thus alpha-tocopherol acetate administration to experimental atherogenic rats could normalize the altered lipid profile of atherogenesis and thereby reduce the risk for infarction.

Effect of lipid antioxidants on rat erythrocyte hemolysis.

Lipid antioxidants, DPPD, DAH, BHT, SQ, retinol and alpha-tocopherol were studied for their effects on normal rat erythrocytes. Retinol, BHT and SQ were found to induce hemolysis while DPPD, DAH and alpha-tocopherol were non-hemolytic. Further more the three antioxidants BHT, SQ and retinol showed a synergistic effect on the lysis. Retinol, BHT or SQ alone, and BHT or SQ along with retinol when administered to rats produced a marked modification of the erythrocyte membrane integrity, simultaneously lowering the levels of membrane bound enzymes--acetyl choline esterase and ATPase. It is concluded that the lipid antioxidants may therefore be classified on the basis of their lytic action in vitro.

Production of aflatoxin m in a liquid medium.

Aspergillus flavus NRRL 3251 grown on modified yeast extract-sucrose medium produced 1 mg of aflatoxin M(1) per 100 ml of medium.

Pathways of glucose catabolism in Mycobacterium smegmatis.

Glucose metabolism in Mycobacterium smegmatis was investigated by the radiorespirometric method and by assaying for key enzymes of the major energy-yielding pathways. Glucose is oxidized in this organism mainly through the Embden-Meyerhof-Parnas pathway, irrespective of the carbon source used for growth. The pentose phosphate pathway plays only a minor role and its extent depends on the carbon source used for growth. Enzymes of glycolytic and oxidative pathways were detected in cells grown on glucose, glycerol, or pyruvate but enzymes of the Entner-Duodroff pathway could be detected only in glucose-grown cells. Labeled acetate is utilized by cells cultured on glucose, glycerol, and pyruvate. In all cases more of C1 of acetate was converted to CO2 while incorporation into cellular constituents was maximum from C2 of acetate.

Effect of coumarins on mitochondrial function.

Several derivatives of coumarin inhibited mitochondrial respiration and ATPase activity. The extent of inhibition depended on the concentration of the coumarins as well as on the substituents of the coumarin ring. Some of the coumarins stimulated ATPase activity, but all of them inhibited uncoupler-stimulated ATPase activity. Coumarins with free or substituted phenolic groups were found to exert profound effects on respiration and ATPase activity.