TY - JOUR
T1 - Nicotine enhances alcoholic fatty liver in mice
T2 - Role of CYP2A5
AU - Chen, Xue
AU - Owoseni, Emmanuel
AU - salamat, Julia
AU - Cederbaum, Arthur I.
AU - Lu, Yongke
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - CYP2A6
KW - Cotinine
KW - Metabolism
KW - Oxidative stress
KW - Reactive oxygen species
KW - Triglyceride
UR - http://www.scopus.com/inward/record.url?scp=85053778499&partnerID=8YFLogxK
U2 - 10.1016/j.abb.2018.09.012
DO - 10.1016/j.abb.2018.09.012
M3 - Article
C2 - 30222954
AN - SCOPUS:85053778499
SN - 0003-9861
VL - 657
SP - 65
EP - 73
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
ER -