Abstract
Isoprene is a normal constituent of human breath and may be derived from the cholesterol synthetic pathway. Acute and chronic lovastatin and a cholesterol-supplemented diet were used to determine whether a mechanistic link exists between isoprene and cholesterol biosynthesisin vivo in humans. The acute effects of lovastatin, a competitive inhibitor of the rate-limiting step of cholesterol biosynthesis, on breath isoprene excretion was determined by administering a single 20, 40 or 80 mg dose of this drug to five healthy male subjects at 8 p.m. and measuring their breath isoprene levels every 4 h for one 24 h cycle before and after treatment. When compared to the baseline cycle, all three doses of lovastatin significantly reduced breath isoprene levels at 6 and 10 h post-drug treatment. Chronic lovastatin therapy (40 mg b.i.d. for 6 wk) reduced 6 a.m. breath isoprene levels (time of maximum baseline value) by 27 ± 9% (SEM) and cholesterol synthesis measured in freshly isolated mononuclear leukocytes (ML) by 12 ± 6%. A cholesterol-supplemented diet (1070 mg, total) ingested for 6 wk reduced breath isoprene excretion and ML sterol synthesis by 16 ± 5 and 19 ± 4%, respectively. The parallel decreases in isoprene excretion and cholesterol synthesis caused by these pharmacologic and dietary means suggest that breath isoprene is derived from the cholesterol synthesis pathway.
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Abbreviations
- DMPP:
-
dimethylallyl pyrophosphate
- HMG-CoA:
-
3-hydroxy-3-methyl-glutaryl coenzyme A
- ML:
-
mononuclear leukocytes
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Stone, B.G., Besse, T.J., Duane, W.C. et al. Effect of regulating cholesterol biosynthesis on breath isoprene excretion in men. Lipids 28, 705–708 (1993). https://doi.org/10.1007/BF02535990
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DOI: https://doi.org/10.1007/BF02535990