DLPC attenuates alcohol-induced cytotoxicity in HepG2 cells expressing CYP2E1.
OBJECTIVE
Alcoholic liver injury was shown to result largely from oxidative stress generated by ethanol metabolism via cytochrome P4502E1 (CYP2E1). Our aim was to determine whether this could be overcome by using dilinoleoylphosphatidylcholine (DLPC), an innocuous antioxidant extracted from soybeans.


METHODS
To address this question, we determined whether DLPC protects against alcohol-induced cytotoxicity in HepG2 cells expressing CYP2E1. A HepG2 subclone (2E1) expressing CYP2E1 and a control subclone (Neo) were exposed for 2 h to DLPC (10 microM), and then 100 mM ethanol was added for 5 days.


RESULTS
Ethanol significantly decreased cell viability in the 2E1 cells and increased apoptosis. These alterations were attenuated by DLPC with the most significant effects in the 2E1 cells. This was accompanied by a reduction of the ethanol-induced oxidative stress, including diminished hydrogen peroxide production in the 2E1, but not in the Neo cells. The mitochondrial membrane potential was significantly diminished by ethanol in both cells. It was also improved after adding DLPC, but only in the 2E1 cells. In these cells, mitochondrial glutathione (GSH) was also partially restored by DLPC, which significantly inhibited the CYP2E1 induction by ethanol.


CONCLUSIONS
DLPC opposes the cytotoxicity induced by alcohol in HepG2 cells expressing CYP2E1, a protective action due, at least in part, to an attenuation of the alcohol-induced oxidative stress and the alteration in the mitochondrial membrane potential. On account of these beneficial effects of DLPC and its innocuity, it is now germane to assess its therapeutic action in alcoholics.
Xu
Youqing
Y
Liver Research Center, Beijing Friendship Hospital, Beijing, China.
Leo
Maria A
MA
Lieber
Charles S
CS
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis* / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010713:Phosphatidylcholines / Q000494:pharmacology*
D010713:Phosphatidylcholines; D000431:Ethanol; C002448:1,2-linoleoylphosphatidylcholine; D019392:Cytochrome P-450 CYP2E1