CHAPTER 17: Multiple Roles of Betaine in Protecting Against Alcohol- Induced Liver Injury
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Published:15 May 2015
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P. G. Thomes, S. M. Bligh, and K. K. Kharbanda, in Betaine: Chemistry, Analysis, Function and Effects, ed. V. R. Preedy, The Royal Society of Chemistry, 2015, pp. 285-310.
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Alcoholic liver disease is a major health problem worldwide. Findings in many laboratories have demonstrated that ethanol feeding impairs several of the multiple steps in methionine metabolism. This results in decreasing the levels of the key methylating agent, hepatic S-adenosylmethionine, while increasing the levels of two toxic metabolites, homocysteine and S-adenosylhomocysteine. These result in serious functional consequences, including reductions in essential methylation reactions and upregulation of the endoplasmic reticulum-stress response. The ultimate outcome is increased fat deposition (steatosis), increased apoptosis, accumulation of damaged proteins and alterations in specific signaling pathways, causing progressive liver damage. Of all the therapeutic modalities presently used to attenuate alcohol-induced liver injury, betaine has been shown to be one the most effective dietary agents in a variety of experimental models of alcoholic liver disease. Betaine, by virtue of its participation in the remethylation of homocysteine, reduces the levels of toxic metabolites, homocysteine and S-adenosylhomocysteine, restores S-adenosylmethionine level and thereby reverses steatosis, prevents apoptosis, reduces accumulation of damaged proteins and attenuates oxidant stress. Thus, betaine is a promising therapeutic agent in relieving defects in hepatic methylation and other alterations associated with chronic alcohol abuse.