Ba. Diebold et al., INFLUENCES OF LOVASTATIN ADMINISTRATION ON THE RESPIRATORY BURST OF LEUKOCYTES AND THE PHOSPHORYLATION POTENTIAL OF MITOCHONDRIA IN GUINEA-PIGS, Biochimica et biophysica acta (G). General subjects, 1200(2), 1994, pp. 100-108
Lovastatin, a cholesterol-lowering drug, decreased plasma cholesterol
and cardiac tissue coenzyme Q(10) levels in guinea pigs given 20 mg pe
r kg body weight twice a day. Plasma cholesterol levels were reduced 4
0% 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 th
e treated, older group were decreased 31% and 37%, respectively. A sig
nificant decrease was not observed in coenzyme Q(10) levels of the you
nger animal group. The potential to phosphorylate ADP to ATP driven by
pyruvate-malate and succinate oxidation was decreased 43% and 45%, re
spectively, for cardiac mitochondria from the treated, 2-year-old anim
als. A decrease in phosphorylation potential was not observed for the
younger group. The respiratory burst of leukocytes isolated from the i
ntraperitoneal cavities of the treated, older animals was decreased 67
%, while leukocytes isolated directly from their blood was decreased 7
6% (Diebold, B., Bhagavan, N. and Guillory, R. (1991) FASEB J. 5, A120
3). 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 possibl
y by modifying the lipid content of the membrane.