Τίτλος:
Effect of 5-HT7 receptor blockade on liver regeneration after 60-70% partial hepatectomy
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: Serotonin exhibits a vast repertoire of actions including cell proliferation and differentiation. The effect of serotonin, as an incomplete mitogen, on liver regeneration has recently been unveiled and is mediated through 5-HT2 receptor. The aim of the present study was to investigate the effect of 5-HT7 receptor blockade on liver regeneration after partial hepatectomy. Methods: Male Wistar rats were subjected to 60-70% partial hepatectomy. 5-HT7 receptor blockade was applied by intraperitoneal administration of SB-269970 hydrochloride two hours prior to and sixteen hours after partial hepatectomy and by intraperitoneal administration of SB-258719 sixteen hours after partial hepatectomy. Animals were sacrificed at different time points until 72 h after partial hepatectomy. Liver regeneration was evaluated by [3H]-thymidine incorporation into hepatic DNA, the mitotic index in hematoxylin-eosin (HE) sections and by immunochemical detection of Ki67 nuclear antigen. Reversion of 5-HT7 blockade was performed by intraperitoneal administration of AS-19. Serum and liver tissue lipids were also quantified. Results: Liver regeneration peaked at 24 h ([3H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and at 32 h (mitotic index in HE sections) in the control group of rats. 5-HT7 receptor blockade had no effect on liver regeneration when applied 2 h prior to partial hepatectomy. Liver regeneration was greatly attenuated when blockade of 5-HT7 receptor was applied (by SB-258719 and SB-269970) at 16 h after partial hepatectomy and peaked at 32 h ([3H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and 40 h (mitotic index in HE sections) after partial hepatectomy. AS-19 administration totally reversed the observed attenuation of liver regeneration. Conclusions: In conclusion, 5-HT7 receptor is a novel type of serotonin receptor implicated in hepatocyte proliferation. © 2014 Tzirogiannis et al.
Συγγραφείς:
Tzirogiannis, K.N.
Kourentzi, K.T.
Zyga, S.
Papalimneou, V.
Tsironi, M.
Grypioti, A.D.
Protopsaltis, I.
Panidis, D.
Panoutsopoulos, G.I.
Περιοδικό:
BMC Gastroenterology
Εκδότης:
BioMed Central Ltd.
Λέξεις-κλειδιά:
Ki 67 antigen; serotonin 7 receptor; 3 [2 [2 (4 methyl 1 piperidinyl)ethyl] 1 pyrrolidinesulfonyl]phenol; 3,N-dimethyl-N-(1-methyl-3-(4-methylpiperidin-1-yl)propyl)benzenesulfonamide; DNA; lipid; phenol derivative; piperidine derivative; serotonin 7 receptor; serotonin antagonist; serotonin receptor; sulfonamide; thymidine, animal experiment; Article; cell proliferation; controlled study; immunochemistry; liver regeneration; male; mitosis index; nonhuman; partial hepatectomy; protein function; quantitative analysis; rat; receptor blocking; animal; blood; cytology; dose response; drug effects; lipid metabolism; liver; liver cell; liver resection; metabolism; physiology; Wistar rat, Animals; Cell Proliferation; DNA; Dose-Response Relationship, Drug; Hepatectomy; Hepatocytes; Lipid Metabolism; Lipids; Liver; Liver Regeneration; Male; Phenols; Piperidines; Rats, Wistar; Receptors, Serotonin; Serotonin Antagonists; Sulfonamides; Thymidine
DOI:
10.1186/s12876-014-0201-2
