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Tobacco Smoke and CYP1A2 Activity in a US Population with Normal Liver Enzyme Levels.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is common among 30% of American adults. Former and current smokers are at higher risk for NAFLD compared to never smokers. The ratio of urine caffeine metabolites to caffeine intake-namely, urine caffeine metabolite indices-has previously been used as a proxy for CYP1A2 activity, which is one of the main liver metabolizing enzymes. CYP1A2 activity is associated with NAFLD progression. No studies to our knowledge have examined the associations of liver enzymes, smoking intensity, and secondhand smoke (SES) with CYP1A2 activity (using caffeine metabolite indices) across smoking status. We analyzed national representative samples from the 2009-2010 National Health and Nutrition Examination Survey (NHANES). Interestingly, even within a normal range, several liver enzymes were associated with caffeine metabolite indices, and patterns of many of these associations varied by smoking status. For instance, within a normal range, aspartate aminotransferase (AST) in never smokers and bilirubin in current smokers were inversely associated with 1-methyluric acid and 5-acetylamino-6-amino-3-methyluracil (URXAMU). Furthermore, we observed a common pattern: across all smoking statuses, higher AST/alanine aminotransferase (AST/ALT) was associated with 1-methyluric acid and URXAMU. Moreover, in current smokers, increased lifelong smoking intensity was associated with reduced caffeine metabolite indices, but acute cigarette exposure as measured by SES levels was associated with increased caffeine metabolite indices among never smokers. In summary, commonly used liver enzyme tests can reflect the CYP1A2 activity even within a normal range, but the selection of these enzymes depends on the smoking status; the associations between smoking and the CYP1A2 activity not only depend on the intensity but also the duration of tobacco exposure.

SUBMITTER: Garduno A

PROVIDER: S-EPMC7956356 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeLiver function of intensive care patients is routinely monitored by static blood pathology. For specific indications, liver specific cytochrome activity may be measured by the commercially available maximum liver function capacity (LiMAx) test via quantification of the cytochrome P450 1A2 (CYP1A2) dependent C-methacetin metabolism. Sedation with the volatile anesthetic isoflurane was suspected to abrogate the correlation of LiMAx test with global liver function. We hypothesized that isoflurane has a CYP1A2-activity and LiMAx test result decreasing effect.MethodsIn this monocentric, observational clinical study previously liver healthy intensive care patients, scheduled to be changed from propofol to isoflurane sedation, were enrolled. LiMAx testing was done before, during and after termination of isoflurane sedation.ResultsThe mean LiMAx value decreased during isoflurane sedation. Septic patients (n = 11) exhibited lower LiMAx values compared to non-septic patients (n = 11) at all time points. LiMAx values decreased with isoflurane from 140 ± 82 to 30 ± 34 µg kg-1 h-1 in the septic group and from 253 ± 92 to 147 ± 131 µg kg-1 h-1 in the non-septic group while laboratory markers did not imply significant hepatic impairment. Lactate increased during isoflurane inhalation without clinical consequence.ConclusionSepsis and isoflurane have independently demonstrated an effect on reducing the hepatic CYP1A2-activity. A network model was constructed that could explain the mechanism through the influence of isoflurane on hypoxia inducible factor (HIF-1α) by upregulation of the hypoxia-inducible pathway and the downregulation of CYP1A2-activity via the ligand-inducible pathway. Thus, the increased anaerobic metabolism may result in lactate accumulation. The influence of isoflurane sedation on the validated correlation of global liver function with CYP1A2-activity measured by LiMAx testing needs to be investigated in more detail.

Project description:Tobacco smoking is endocrine-disrupting and may interfere with vitamin D endocrine systems (VDES), but supporting evidence is limited and inconsistent. Also, there is a lack of evidence on whether the association between tobacco smoke exposure and VD levels exhibit temporal variation. Data from the National Health and Nutrition Examination Survey was used to evaluate the association between tobacco smoke exposure and VD levels among US general participants from 2001 to 2014. We examined the linear association between serum cotinine and 25(OH)D concentrations, as well as relationship between tobacco smoke exposure categories (active, passive, non-smoking) with VD status (deficiency, inadequacy, sufficiency, intoxication), and assessed whether specific gender, age (3-11, 12-19, 20-59, ≥ 60 years), ethnicity/race, or body mass index (BMI) groups were disproportionately impacted. During 2001-2004, a decrease in both serum cotinine and passive smoking prevalence was observed, with a stabilized active smoking rate. The estimates for the association between tobacco smoke exposure and suboptimal VD levels increased over the study period. Overall results indicated that serum cotinine was negatively associated with 25(OH)D in all participants. Tobacco smoke exposure, including both active and passive smoking exposure, was associated with increased risk of VD deficiency. Moreover, active smoking was additionally related to enhanced risk of VD inadequacy. These associations showed some age and gender differences, with consistent and stronger associations observed in female adults. In contrast, effects of tobacco smoke exposure on VD levels were mostly negative or non-significant among children and adolescents aged 3-19 years. The percentage of US general population with active smoking exposure stabilized over the 14-year period and was still high. Tobacco smoke exposure may disrupt vitamin D levels with an increasing temporal trend in the risk. Our results also provided initial evidence of smoking exposure on VD intoxication, which needs to be further verified. Convincing studies have linked tobacco use exposure, to dysfunctional VDES accompanied with declined serum levels of VD metabolites. However, evidence on the association between tobacco smoke exposure and VD status was rather limited and inconsistent, and there were no researches to date that estimated the temporal variation of the association as well as the effects of smoke exposure on VD intoxication. This study analyzed national survey data, to evaluate the temporal trends in effects of tobacco smoke exposure on VD levels over a decade, and to comprehensively assess the impacts of tobacco smoke exposure on VD levels across specific subgroups. The evidence suggests that the prevalence of active smoking exposure stabilized over the 14-year period and was still high. Moreover, tobacco smoke exposure may disrupt vitamin D levels among general population, with an increasing temporal trend and age-, gender-differences in risk.

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Tobacco Smoke and CYP1A2 Activity in a US Population with Normal Liver Enzyme Levels.

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