RESUMO
1. A high cholesterol diet caused guinea pig erythrocytes to become sensitive to lysis by cholesterol oxidase (CO), a protein not hemolytic to normal cells. 2. Lysis was associated with conversion of membrane cholesterol to its oxidation product (delta-4-cholesten-3-one). 3. Intravenous injection of CO to hypercholesterolemic guinea pigs produced a reduction in serum cholesterol, but was not lethal as it was in rabbits. 4. Homogenized spleen, liver and kidney from the hyperlipidemic animals were sensitive to in vitro cholesterol oxidation while tissues from non-lipemic animals were resistant to modification.
Assuntos
3-Hidroxiesteroide Desidrogenases/toxicidade , Colesterol Oxidase/toxicidade , Eritrócitos/efeitos dos fármacos , Hipercolesterolemia/sangue , Animais , Sobrevivência Celular/efeitos dos fármacos , Colesterol na Dieta , Cobaias , Hipercolesterolemia/etiologia , Rim/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Baço/metabolismoRESUMO
Intravenous injection of cholesterol oxidase into hyperlipidemic rabbits in which aortic atheromatous lesions have been induced by dietary means is lethal within hours, whereas injection of the same enzyme into normal rabbits has no visible adverse effect. The lethal effect of the enzyme is explicable by the finding that injection of cholesterol-oxidase treated low-density lipoprotein kills normal rabbits, in contrast to untreated low-density lipoprotein which does not. Enzymically oxidized low-density lipoprotein was also found to be cytotoxic for two human cell lines and for cultured bovine aortic endothelial cells. We suggest that in vivo enzymic conversion of low-density lipoprotein cholesterol to low-density lipoprotein cholestenone may possibly play a role in the initiation of atheromatous lesions in humans.
Assuntos
3-Hidroxiesteroide Desidrogenases/toxicidade , Colesterol Oxidase/toxicidade , Colesterol na Dieta , Lipoproteínas LDL/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol Oxidase/metabolismo , Replicação do DNA/efeitos dos fármacos , Cobaias , Humanos , Camundongos , Oxirredução , CoelhosRESUMO
Cholesterol oxidase (3 beta-hydroxysteroid oxidase) from the Actinomyces lavendulae mycelium oxidizes cholesterol of blood serum in vitro. The half-inactivation time for the enzyme in blood serum (37 degrees) is 90 min. After intravenous injection of the enzyme (1--2 units per kg) to rabbits with experimental hypercholesterinemia the cholesterol content in the blood is decreased directly proportional to the single dose of the enzyme and duration of injection. After 6-8 injections the level of non-esterified and total cholesterol is drastically decreased (by 90-97% and 65-68%, respectively). The acute toxicity of cholesterol oxidase preparations for mice decreases depending on the degree of the enzyme purification.
Assuntos
3-Hidroxiesteroide Desidrogenases/farmacologia , Colesterol Oxidase/farmacologia , Colesterol/sangue , Actinomyces/enzimologia , Animais , Colesterol Oxidase/metabolismo , Colesterol Oxidase/toxicidade , Cinética , Camundongos , CoelhosRESUMO
Cholesterol oxidase (3 beta-hydrosteroid oxidase), isolated from Actinomyces lavendulae, oxidized unesterified cholesterol in rabbit blood serum without detergents in vitro. Intravenous administration of the enzyme into hypercholesterolemic rabbits at a dose of 0.5-2.0 un/kg decrease distinctly the cholesterol content in blood. The rate of the decrease depended on the dose of the preparation. Acute toxicity of the cholesterol oxidase preparations for mice correlated with the degree of purification of the enzyme. Cholesterol oxidase from Act. lavendulae may be considered as a potential hypocholesterolemic drug.
