Document Detail

Stimulation of oval cell and hepatocyte proliferation by exogenous bombesin and neurotensin in partially hepatectomized rats.
MedLine Citation:
PMID:  22180848     Owner:  NLM     Status:  PubMed-not-MEDLINE    
AIM: To investigate the effect of the neuropeptides bombesin (BBS) and neurotensin (NT) on oval cell proliferation in partially hepatectomized rats not pretreated with a known hepatocyte inhibitor.
METHODS: Seventy male Wistar rats were randomly divided into five groups: I = controls, II = sham operated, III = partial hepatectomy 70% (PHx), IV = PHx + BBS (30 μg/kg per day), V = PHx + NT (300 μg/kg per day). Forty eight hours after liver resection, portal endotoxin levels and hepatic glutathione redox state were determined. α-fetoprotein (AFP) mRNA (in situ hybridisation), cytokeratin-19 and Ki67 antigen expression (immunohistochemistry) and apoptosis (TUNEL) were evaluated on liver tissue samples. Cells with morphological features of oval cells that were cytokeratin-19 (+) and AFP mRNA (+) were scored in morphometric analysis and their proliferation was recorded. In addition, the proliferation and apoptotic rates of hepatocytes were determined.
RESULTS: In the control and sham operated groups, oval cells were significantly less compared to groups III, IV and V (P < 0.001). The neuropeptides BBS and NT significantly increased the proliferation of oval cells compared to group III (P < 0.001). In addition, BBS and NT induced a significant increase of hepatocyte proliferation (P < 0.001), whereas it decreased their apoptotic activity (P < 0.001) compared to group III. BBS and NT significantly decreased portal endotoxemia (P < 0.001) and increased the hepatic GSH: GSSG ratio (P < 0.05 and P < 0.001, respectively) compared to group III.
CONCLUSION: BBS and NT stimulated oval cell proliferation in a model of liver regeneration, without use of concomitant suppression of hepatocyte proliferation as oval cell activation stimuli, and improved the hepatocyte regenerative response. This peptides-induced combined stimulation of oval cell and hepatocyte proliferation might serve as a possible treatment modality for several liver diseases.
Stelios F Assimakopoulos; Athanassios C Tsamandas; Ilias H Alexandris; Christos Georgiou; Constantine E Vagianos; Chrisoula D Scopa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  World journal of gastrointestinal pathophysiology     Volume:  2     ISSN:  2150-5330     ISO Abbreviation:  World J Gastrointest Pathophysiol     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-19     Completed Date:  2012-08-15     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101547471     Medline TA:  World J Gastrointest Pathophysiol     Country:  China    
Other Details:
Languages:  eng     Pagination:  146-54     Citation Subset:  -    
Department of Internal Medicine, University Hospital of Patras, Patras 26504, Greece.
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