Influence of buthionine sulfoximine, S-adenosylmethionine and glutathione on liver regeneration following partial hepatectomy.
This study was designed to evaluate the effect of derangement in methionine metabolism, and the effects of S-adenosylmethionine (SAM) and glutathione (GSH) on liver regeneration. Rats were treated immediately and 6 h after 70% hepatectomy (PH) as follows: (1) SAM, (2) GSH, (3) buthionine sulfoximine (BSO; inhibitor of SAM and GSH synthesis), (4) BSO + SAM, (5) BSO + GSH, and (6) buffer solution (B). The control group consisted of laparotomized animals treated with B. The increase in hepatic DNA synthesis, hepatocyte mitotic activity, and protein synthesis were observed in PH rats while in BSO rats, a delayed onset of liver regeneration was observed. SAM induced an earlier onset of hepatocyte mitotic activity, and reduced the inhibitory effect of BSO. GSH treatment exerted an inhibitory effect on liver regeneration and worsened the negative effect of BSO. It is concluded that derangement in methionine metabolism can impair the development of liver regeneration. The data also demonstrate the favourable effect of SAM and negative effect of GSH.
Holecek
M
M
Charles University School of Medicine, Department of Physiology and Radioisotope Laboratory, Hradec Králové, Czech Republic. holecek@lfhk.cuni.cz
Skopec
F
F
Sprongl
L
L
D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology*; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects; D007930:Leucine / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008940:Mitotic Index; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000494:pharmacology*
D000596:Amino Acids; D000963:Antimetabolites; D019328:Buthionine Sulfoximine; D012436:S-Adenosylmethionine; D004247:DNA; D005978:Glutathione; D007930:Leucine