INFLUENCES OF LOVASTATIN ADMINISTRATION ON THE RESPIRATORY BURST OF LEUKOCYTES AND THE PHOSPHORYLATION POTENTIAL OF MITOCHONDRIA IN GUINEA-PIGS

Lovastatin, a cholesterol-lowering drug, decreased plasma cholesterol and cardiac tissue coenzyme Q(10) levels in guinea pigs given 20 mg per kg body weight twice a day. Plasma cholesterol levels were reduced 40% in animals 2 to 4 months of age and 61% in animals 2 years of age. Coenzyme Q(10) values in cardiac muscle and cardiac mitochondria of the treated, older group were decreased 31% and 37%, respectively. A significant decrease was not observed in coenzyme Q(10) levels of the younger animal group. The potential to phosphorylate ADP to ATP driven by pyruvate-malate and succinate oxidation was decreased 43% and 45%, respectively, for cardiac mitochondria from the treated, 2-year-old animals. A decrease in phosphorylation potential was not observed for the younger group. The respiratory burst of leukocytes isolated from the intraperitoneal cavities of the treated, older animals was decreased 67%, while leukocytes isolated directly from their blood was decreased 76% (Diebold, B., Bhagavan, N. and Guillory, R. (1991) FASEB J. 5, A1203). In contrast to the intact leukocytes, the superoxide production of the cell-free systems prepared from leukocytes isolated from treated and untreated animals did not differ significantly. These observations suggest that in vivo lovastatin may not directly affect the leukocyte superoxide generating system, but may influence it indirectly possibly by modifying the lipid content of the membrane.