Effect of betaine supplementation on changes in hepatic metabolism of sulfur-containing amino acids and experimental cholestasis induced by alpha-naphthylisothiocyanate.
Alterations in the hepatic metabolism of sulfur amino acids in experimental cholestasis induced by alpha-naphthylisothiocyanate (ANIT) (100 mg/kg, po) were monitored in male mice for 1 week. We also examined the effects of betaine supplementation (1% in drinking water) for 2 weeks on the hepatotoxicity and changes in the sulfur amino acid metabolism induced by ANIT treatment. Acute ANIT challenge elevated the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, and total bilirubin contents from 5 h after the treatment, reaching a peak at t = 48-72 h. Hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels were decreased significantly in a manner almost inversely proportional to the changes in serum parameters measured to determine the ANIT-induced toxicity. Hepatic glutathione and cysteine levels were elevated at t = 120 h after the treatment. Betaine supplementation blocked or significantly attenuated induction of the hepatotoxicity by ANIT. The decrease in SAM and SAH levels was also inhibited by betaine intake. The results indicate that betaine supplementation may antagonize the induction of experimental cholestasis and changes in the metabolism of sulfur amino acids associated with ANIT treatment. The underlying mechanism and pharmacological significance of its action are discussed.
Kim
Young C
YC
College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul 151-742, South Korea. youckim@snu.ac.kr
Jung
Young S
YS
Kim
Sang K
SK
D015058:1-Naphthylisothiocyanate / Q000633:toxicity; D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000603:Amino Acids, Sulfur / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001622:Betaine / Q000008:administration & dosage / Q000494:pharmacology*; D001663:Bilirubin / Q000378:metabolism; D002779:Cholestasis / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D019587:Dietary Supplements; D005978:Glutathione / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism
D000603:Amino Acids, Sulfur; D001622:Betaine; D015058:1-Naphthylisothiocyanate; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005978:Glutathione; D003545:Cysteine; D001663:Bilirubin