Isoprene in expired breath as a marker of cholesterol synthesis for the statin therapy monitoring

Zadák, Z; Hyšpler, Radomı́r; Crhova, S.; Gasparič, J.; Čížková, Martina; Balasova, V.

doi:10.1016/s0021-9150(99)80791-6

Cited by 8 publications

(6 citation statements)

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“…Deneris et al (5) have demonstrated the in vitro synthesis of isoprene from DL-mevalonate and proposed that breath isoprene is linked to cholesterol biosynthesis, which relies on the mevalonate pathway. Administration of the drug lovastatin or other statins, competitive inhibitors of the rate-limiting step of cholesterol biosynthesis in humans, has been demonstrated to suppress isoprene in the breath (22,26). Small amounts of breath isoprene may arise from peroxidation of the cholesterol precursor squalene (21).…”

Section: Discussionmentioning

confidence: 99%

Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling

Karl¹,

Prazeller²,

Mayr³

et al. 2001

Journal of Applied Physiology

240

227

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Numerous publications have described measurements of breath isoprene in humans, and there has been a hope that breath isoprene analyses could be a noninvasive diagnostic tool to assess blood cholesterol levels or cholesterol synthesis rate. However, significant analytic problems in breath isoprene analysis and variability in isoprene levels with age, exercise, diet, etc., have limited the usefulness of these measurements. Here, we have applied proton transfer reaction-mass spectrometry to this problem, allowing on-line detection of breath isoprene. We show that breath isoprene concentration increases within a few seconds after exercise is started as a result of a rapid increase in heart rate and then reaches a lower steady state when breath rate stabilizes. Additional experiments demonstrated that increases in heart rate associated with standing after reclining or sleeping are associated with increased breath isoprene concentrations. An isoprene gas-exchange model was developed and shows excellent fit to breath isoprene levels measured during exercise. In a preliminary experiment, we demonstrated that atorvastatin therapy leads to a decrease in serum cholesterol and low-density-lipoprotein levels and a parallel decrease in breath isoprene levels. This work suggests that there is constant endogenous production of isoprene during the day and night and reaffirms the possibility that breath isoprene can be a noninvasive marker of cholesterologenesis if care is taken to measure breath isoprene under standard conditions at constant heart rate.

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Section: Discussionmentioning

confidence: 99%

Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling

Karl¹,

Prazeller²,

Mayr³

et al. 2001

Journal of Applied Physiology

240

227

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“…Although breath isoprene is of endogenous origin (30,(33)(34)(35)(36)(37)(38)(39) and is not produced within the airways (40), we do not know all its different biochemical sources. Different evidence suggests that isoprene is a by-product of cholesterol biosynthesis (35)(36)(37)(41)(42)(43)(44)(45)(46)(47)(48)(49). Small amounts of this VOC may arise from peroxidation of squalene, a cholesterol precursor (41).…”

Section: Menmentioning

confidence: 99%

“…Administration of lipid-lowering (statin) therapy results in a proportional decrease in breath isoprene and plasma total cholesterol concentrations in healthy volunteers (43,49) and intensive care patients (48). On the other hand, a cholesterol-rich diet also decreases isoprene levels in exhaled breath (43) due to feedback inhibition of HMG-CoA reductase (3hydroxy-3-methyl-glutaryl-CoA reductase) (50,51).…”

Section: Menmentioning

confidence: 99%

Breath isoprene – aspects of normal physiology related to age, gender and cholesterol profile as determined in a proton transfer reaction mass spectrometry study

Kushch¹,

Arendacká²,

Štolc³

et al. 2008

Clinical Chemistry and Laboratory Medicine

137

149

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“…Isoprene is an interesting and important VOC both in atmospheric chemistry and human breath gas analysis. [19][20][21][22] For instance, the study of isoprene-OH-initiated peroxy radial spectroscopy and kinetics offers insight into the formation of ground-level ozone; 23 and isoprene is the most abundant VOC in human breath gas and has been identified as a biomarker related to blood cholesterol levels. 24 Isoprene has well-documented absorption spectra in the UV region, but its NIR spectra are unknown.…”

Section: Resultsmentioning

confidence: 99%

Absorption Cross-Sections of the C—H Overtone of Volatile Organic Compounds: 2 Methyl-1,3-Butadiene (Isoprene), 1,3-Butadiene, and 2,3-Dimethyl-1,3-Butadiene

2007

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Many molecules or transient radicals have well-documented absorption cross-sections in the ultraviolet (UV) region, but their absorption cross-sections in the near-infrared (NIR) region are much less often known and are difficult to measure. We propose a method to determine the unknown NIR absorption cross-sections using the known absorption cross-sections in the UV region, in which single-path UV absorption spectroscopy and NIR continuous wave cavity ringdown spectroscopy (cw-CRDS) are employed in a cross-arm reaction chamber for simultaneous measurements. Without knowing the actual sample partial pressures (or concentrations), the NIR absorption cross-sections can be accurately determined through the two sets of measurements. The method is demonstrated by measuring the NIR absorption cross-section of the first overtone of the asymmetric C-H stretch of 2-methyl-1,3-butadiene (isoprene) (3.24 (+/-0.16) x 10(-22) cm(2) molecule(-1)) at 1651.52 nm using the known value of the absorption cross-section at 220 nm. The diode laser wavelength was calibrated by atmospheric cavity ringdown spectra of CH(4), CO(2), and H(2)O. By comparison with sample pressure measurements, this method can also be used as a pressure calibration means for the reaction chamber, and this has been demonstrated with two additional measurements of the absorption cross-sections of 1,3-butadiene and 2,3-dimethyl-1,3-butadiene (2.50 (+/- 0.08) x 10(-22) and 2.82 (+/-0.16) x 10(-22) cm(2) molecule(-1), respectively) at 1651.52 nm. The applicability of the method to determining absorption cross-sections using the simultaneous measurements of cw-CRDS and single-path absorption spectroscopy is discussed.

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Isoprene in expired breath as a marker of cholesterol synthesis for the statin therapy monitoring

Cited by 8 publications

References 0 publications

Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling

Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling

Breath isoprene – aspects of normal physiology related to age, gender and cholesterol profile as determined in a proton transfer reaction mass spectrometry study

Absorption Cross-Sections of the C—H Overtone of Volatile Organic Compounds: 2 Methyl-1,3-Butadiene (Isoprene), 1,3-Butadiene, and 2,3-Dimethyl-1,3-Butadiene

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