Nicotine enhances alcoholic fatty liver in mice: Role of CYP2A5.

Abstract

Tobacco and alcohol are often co-abused. Nicotine can enhance alcoholic fatty liver, and CYP2A6 (CYP2A5 in mice), a major metabolism enzyme for nicotine, can be induced by alcohol. CYP2A5 knockout (cyp2a5-/-) mice and their littermates (cyp2a5+/+) were used to test whether CYP2A5 has an effect on nicotine-enhanced alcoholic fatty liver. The results showed that alcoholic fatty liver was enhanced by nicotine in cyp2a5+/+ mice but not in the cyp2a5-/- mice. Combination of ethanol and nicotine increased serum triglyceride in cyp2a5+/+ mice but not in the cyp2a5-/- mice. Cotinine, a major metabolite of nicotine, also enhanced alcoholic fatty liver, which was also observed in cyp2a5+/+ mice but not in the cyp2a5-/- mice. Nitrotyrosine and malondialdehyde (MDA), markers of oxidative/nitrosative stress, were induced by alcohol and were further increased by nicotine and cotinine in cyp2a5+/+ mice but not in the cyp2a5-/- mice. Reactive oxygen species (ROS) production during microsomal metabolism of nicotine and cotinine was increased in microsomes from cyp2a5+/+ mice but not in microsomes from cyp2a5-/- mice. These results suggest that nicotine enhances alcoholic fatty liver in a CYP2A5-dependent manner, which is related to ROS produced during the process of CYP2A5-dependent nicotine metabolism.

• Authors: Xue Chen, Emmanuel Owoseni, Julia Salamat, Arthur I Cederbaum, Yongke Lu
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 657 Pg. 65-73 (11 01 2018) ISSN: 1096-0384 [Electronic] United States
• PMID: 30222954 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Ethanol
• Nicotine
• Aryl Hydrocarbon Hydroxylases
• Cyp2a5 protein, mouse
• Cytochrome P450 Family 2
• Cotinine

Topics

• Animals
• Aryl Hydrocarbon Hydroxylases (genetics, metabolism)
• Chemical and Drug Induced Liver Injury (etiology, metabolism)
• Cotinine (adverse effects, blood, metabolism, urine)
• Cytochrome P450 Family 2 (genetics, metabolism)
• Ethanol (toxicity)
• Fatty Liver, Alcoholic (etiology, metabolism)
• Female
• Gene Knockout Techniques
• Liver (metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Microsomes, Liver (metabolism)
• Nicotine (adverse effects, metabolism)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)