التفاصيل البيبلوغرافية
| العنوان: |
Nicotine enhances alcoholic fatty liver in mice: Role of CYP2A5. |
| المؤلفون: |
Chen, Xue1 chenx1@etsu.edu, Owoseni, Emmanuel2 owosenie@etsu.edu, salamat, Julia2 salamat@etsu.edu, Cederbaum, Arthur I.3 Arthur.cederbaum@mssm.edu, Lu, Yongke1,4 luy004@etsu.edu |
| المصدر: |
Archives of Biochemistry & Biophysics. Nov2018, Vol. 657, p65-73. 9p. |
| مصطلحات موضوعية: |
*NICOTINE, *FATTY liver, *OXIDATIVE stress, *TRIGLYCERIDES, *FIBROBLASTS |
| مستخلص: |
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. Graphical abstract Image 1 Highlights • Nicotine augments alcoholic fatty liver, which is CYP2A5-dependent. • Nicotine metabolite cotinine also enhances alcoholic fatty liver in a CYP2A5-dependent manner. • Metabolism of nicotine and cotinine by CYP2A5 produces ROS. • Nicotine and cotinine enhance alcoholic fatty liver via elevated oxidative stress. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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