The effect of taurine depletion by beta-alanine treatment on the susceptibility to ethanol-induced hepatic dysfunction in rats.
Alcohol was administered chronically to female Sprague-Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in significant hepatic steatosis and lipid peroxidation. Beta-alanine, when co-administered with alcohol, seemed to increase hepatic steatosis, as assessed histologically, but decreased triglyceride levels as measured biochemically. In addition, beta-alanine and especially alcohol co-administered with beta-alanine, significantly increased homocysteine and cysteine excretion into urine throughout the 28-day period of ethanol administration. Serum homocysteine levels were significantly higher in alcohol- and alcohol plus beta-alanine-treated animals compared to pair-fed control animals. Alcohol did not affect the urinary excretion of taurine, except after 21 days, when levels were reduced. Levels of liver taurine were markedly depleted in animals receiving alcohol and particularly alcohol plus beta-alanine, compared to pair-fed controls. Liver and serum taurine levels were also markedly depleted in animals receiving beta-alanine and alcohol plus beta-alanine, compared to non-beta-alanine-treated animals. There was evidence of slight cholestasis in animals treated with alcohol and more so with alcohol plus beta-alanine, as indicated by raised serum alkaline phosphatase and bile acids. These in vivo findings demonstrate for the first time that animals treated with beta-alanine may be more susceptible to ethanol-induced hepatic dysfunction, possibly as a result of taurine depletion.
Kerai
M D
MD
Pharmacy Department, Kings' College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 8WA, UK.
Waterfield
C J
CJ
Kenyon
S H
SH
Asker
D S
DS
Timbrell
J A
JA
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003545:Cysteine / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005235:Fatty Liver, Alcoholic / Q000209:etiology; D005260:Female; D006710:Homocysteine / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000187:drug effects* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015091:beta-Alanine / Q000494:pharmacology*
D002492:Central Nervous System Depressants; D014280:Triglycerides; D006710:Homocysteine; D015091:beta-Alanine; D013654:Taurine; D000431:Ethanol; D003545:Cysteine