Role of Medium‐Chain Triglycerides in the Alcohol‐Mediated Cytochrome P450 2E1 Induction of Mitochondria

Abstract

Mitochondria participate in the induction of CYP2E1 by alcohol and contribute to lipid peroxidation and GSH depletion. Thus, lipid composition of the diet is an important determinant for the beneficial effect of MCT, with a diet containing a mixture of LCT/MCT being ineffective.

Role of CYP2E1 in Mitochondrial Dysfunction and Hepatic Injury by Alcohol and Non-Alcoholic Substances

“…Interestingly, when compared to other members of cytochrome P450 genes, CYP2E1 possesses a remarkably high NADPH oxidase activity, resulting in increased production of reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ), hydroxyl radical, and superoxide anion [16, 17], all of which can produce peroxynitrite through interaction with nitric oxide, or under toxic conditions, increase the levels of lipid peroxidation [18–20]. The increased ROS can exert deleterious effects on the cell functions and even survival mainly through damaging cellular and mitochondrial macromolecules including mitochondrial DNA.…”

Cytochrome P450 2E1: Its Clinical Aspects and a Brief Perspective on the Current Research Scenario

“…Although the list of the studies discussed here is not complete and the studies which have not been represented do not account for lesser importance of the Alcohol induced liver injury/alcohol induced liver cell toxicity Salmela et al ( 1998 ) , Takahashi et al ( 1993 ) , Tsutsumi et al ( 1993 ) , Koivisto et al ( 1996 ) , Ma et al ( 1991 ) , Aleynik et al ( 1999 ) , Mi et al ( 2000 ) , Aleynik and Lieber ( 2001 ) , Xu et al ( 2005 ) , Lieber et al ( 2007b ) , Dai et al ( 1993 ) , Carroccio et al ( 1994 ) , Wu and Cederbaum ( 1993b , Kukielka and Cederbaum ( 1994 ) , Lu et al ( , 2010 , Bai and Cederbaum ( 2006 ) , Nieto et al ( 2000 ) , Osna et al ( 2003Osna et al ( , 2005Osna et al ( , 2007Osna et al ( , 2008Osna et al ( , 2009Osna et al ( , 2010 , Castillo et al ( 1992 ) , Gebhardt et al ( 1997 ) , Oneta et al ( 2002 ) , Wang et al ( 2009 ) , CurryMcCoy et al ( 2010 ) , Wan et al ( 1995 ) , Morimoto et al ( 1993Morimoto et al ( , 1994Morimoto et al ( , 1995a , Gouillon et al ( 1999Gouillon et al ( , 2000 , Bardag-Gorce et al ( 2000, 2006 , Donohue et al ( 2006 ) , Garige et al ( 2005 ) , …”

“…When MCT replaces all the fat, like in the alcohol-MCT 32% group, CYP2E1 is signi fi cantly reduced both in mitochondria and microsomes (Lieber et al 2007b ) . Thus, mitochondria participate in the induction of CYP2E1 by alcohol and contribute to lipid peroxidation and GSH depletion and a diet rich in MCT is bene fi cial in ameliorating injury.…”

“…In rats fed either 32% of calories as dietary long-chain triglycerides (LCT) (alcohol), or 16% as LCT + 16% as medium-chain triglycerides (MCT) (alcohol-MCT 16%), or 32% as MCT only (alcohol-MCT 32%), both alcohol and alcohol-MCT 16% groups have a signi fi cant increase in mitochondrial and microsomal CYP2E1 (Lieber et al 2007b ) . When MCT replaces all the fat, like in the alcohol-MCT 32% group, CYP2E1 is signi fi cantly reduced both in mitochondria and microsomes (Lieber et al 2007b ) .…”

Ações do óleo de peixe e triglicerídeos de cadeia média na esteatose hepática e estresse oxidativo induzidos pela dieta hiperlipídica em ratos

“…O mecanismo proposto que justifica o uso dos TCMs na esteatose hepática é a prevenção da inibição da -oxidação de ácidos graxos (Lieber, Cao et al 2007;Lieber, DeCarli et al 2008). …”