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A Randomized Trial of Effects of Alcohol on Cytochrome P450 Eicosanoids, Mediators of Inflammation Resolution, and Blood Pressure in Men
Author(s) -
Barden Anne E.,
Chavez Venus,
Phillips Michael,
Mas Emilie,
Beilin Lawrence J.,
Croft Kevin D.,
Mori Trevor A.,
Puddey Ian B.
Publication year - 2017
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13466
Subject(s) - eicosapentaenoic acid , docosahexaenoic acid , arachidonic acid , eicosanoid , oxidative stress , isoprostane , medicine , isoprostanes , endocrinology , inflammation , blood pressure , epoxygenase , chemistry , polyunsaturated fatty acid , cytochrome p450 , lipid peroxidation , biochemistry , fatty acid , enzyme , metabolism
Background Cardiovascular effects of alcohol consumption may be influenced by both pro‐ and anti‐inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure ( BP ), oxidative stress, and 20‐hydroxyeicosatetraenoic acid (20‐ HETE ), a vasoconstrictor and pro‐inflammatory eicosanoid synthesized by cytochrome P450 (CYP450) enzymes from arachidonic acid. This study in men examined the effect of consuming red wine ( RW ) on BP in relation to changes in 20‐ HETE , oxidative stress (F 2 ‐isoprostanes), markers of inflammation, anti‐inflammatory CYP 450 epoxyeicosatrienoic acids ( EET s), and specialized pro‐resolving mediators of inflammation ( SPM s) derived from eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ). Methods Normotensive men ( n = 22) were randomly allocated to drink RW (375 ml/d) or the equivalent volume of dealcoholized red wine ( DRW ) or water for 4 weeks in a 12‐week, 3‐period crossover trial. BP , heart rate, 20‐ HETE , F 2 ‐isoprostanes, and SPM were measured at baseline, 4, 8, and 12 weeks. Results Drinking RW increased BP ( p < 0.05), plasma and urinary 20‐ HETE ( p < 0.05), plasma F 2 ‐isoprostanes ( p < 0.0001), and the SPM s 18‐hydroxyeicosapentaenoic acid (18‐ HEPE ) from EPA , and resolvin D1 (RvD1) and 17R‐resolvin D1 (17R‐RvD1) from DHA (all p < 0.05) compared with DRW and water. EET s and high‐sensitivity C‐reactive protein were unaffected by RW . Plasma 18‐ HEPE was positively related to urinary 20‐ HETE ( p < 0.008) only after RW . Conclusions This study has shown that men consuming moderate‐to‐high alcohol as RW for 4 weeks had increased BP , 20‐ HETE , and oxidative stress, as well as specific SPM that resolve inflammation. These paradoxical findings require further studies to determine whether alcohol stimulates different CYP 450 enzymes and whether the findings can be replicated in females.