The hepatoprotective effect of hepatic stimulator substance (HSS) against liver regeneration arrest induced by acute ethanol intoxication.
Male Wistar rats were randomized to receive ethanol (2.5 ml/kg by gastric intubation every 8 hr; group I), equal volumes of isocaloric to ethanol sucrose solution (group II), or ethanol and HSS (100 mg/kg intraperitoneally 10 and 16 hr after partial hepatectomy; groups III and IV, respectively) for up to 96 hr after partial hepatectomy, with ethanol administration starting 1 hr prior to partial hepatectomy. Animals were killed at 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, and 96 hr after partial hepatectomy. The rate of liver regeneration was evaluated by the mitotic index in H&E-stained sections, immunochemical detection of Ki67 nuclear antigen, rate of [3H]thymidine incorporation into hepatic DNA, and liver thymidine kinase enzymatic activity. The biological activity of HSS in groups I and II rats was evaluated using a bioassay. Ethanol administration arrested liver regeneration during the first 32 hr after partial hepatectomy and suppressed HSS activity throughout the period examined. Liver regeneration progressed after 32 hr despite the low levels of HSS activity. HSS administration at 10 and 16 hr reversed liver regeneration arrest induced by ethanol. Acute ethanol administration induces cell cycle arrest during the first 32 hr after partial hepatectomy and suppression of HSS biological activity seems to contribute to this effect. HSS administration reversed the inhibitory effect of ethanol on liver regeneration and caused synchronized entrance of hepatocytes in the S phase of the cell cycle. HSS seems to participate in the network of growth factors controlling the G1/S cell cycle checkpoint.
Kondili
Vasiliki G
VG
Department of Experimental Pharmacology, Medical School, Athens University, 75 Mikras Asias Street, Athens 115 27, Greece.
Tzirogiannis
Konstantinos N
KN
Androutsos
Christos D
CD
Papadimas
George K
GK
Demonakou
Maria D
MD
Hereti
Rosa I
RI
Manta
Georgia A
GA
Kourentzi
Kalliopi T
KT
Triantaphyllou
Maro I
MI
Panoutsopoulos
Georgios I
GI
D000208:Acute Disease; D000435:Alcoholic Intoxication / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D000431:Ethanol / Q000633:toxicity*; D006133:Growth Substances / Q000502:physiology*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008934:Mitogens / Q000502:physiology*; D008940:Mitotic Index; D010455:Peptides / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016196:S Phase / Q000502:physiology
D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D008934:Mitogens; D010455:Peptides; C073456:hepatic stimulator substance; D000431:Ethanol
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