Hepatotrophic factors reduce hepatic fibrosis in rats.
BACKGROUND
Hepatic fibrosis occurs in response to several aggressive agents and is a predisposing factor in cirrhosis. Hepatotrophic factors were shown to stimulate liver growth and to restore the histological architecture of the liver. They also cause an improvement in liver function and accelerate the reversion of fibrosis before it progresses to cirrhosis.


OBJECTIVE
To test the effects of hepatic fibrosis solution composed by amino acids, vitamins, glucose, insulin, glucagon and triiodothyronine on hepatic fibrosis in rats.


METHODS
Fibrosis was induced in rats by gastric administration of dimethylnitrosamine (10 mg/kg) for 5 weeks. After liver biopsy, the rats received either hepatotrophic factors solution (40 mg/kg/day) or saline solution for 10 days by intraperitoneal injection. Blood samples and liver fragments were collected for hepatic function analysis, standard histopathology evaluation, and morphometric collagen quantification.


RESULTS
Rats in the hepatotrophic factors group showed a decrease of the histopathological components of fibrosis and an increase of their hepatic mass (12.2%). There was no development of neoplasic lesions in both groups. Compared with the saline group, the hepatotrophic factors group also had a decrease of blood levels of hepatic-lesion markers (AST, ALT) and a decrease of collagen content in the portal spaces (31.6%) and perisinusoidal spaces (42.3%), as well as around the hepatic terminal vein (57.7%). Thus, hepatotrophic factors administration in the portal blood promoted a regenerative hepatic response, with an overall reduction of the volumetric density of collagen, improved hepatic function, and a general improvement in the histopathological aspects of fibrosis.


CONCLUSIONS
Taken together, these results suggest the potential therapeutic use of this hepatotrophic factors solution to treat chronic liver diseases.
Cogliati
Bruno
B
Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo, São Paulo, SP, Brazil. bcogliati@usp.br
Pereira
Hélder de Moraes
Hde M
Dagli
Maria Lúcia Zaidan
ML
Parra
Osório Miguel
OM
Silva
José Roberto Machado Cunha da
JR
Hernandez-Blazquez
Francisco Javier
FJ
D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D003094:Collagen / Q000032:analysis*; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D007287:Inorganic Chemicals / Q000008:administration & dosage*; D008106:Liver Cirrhosis, Experimental / Q000473:pathology / Q000628:therapy*; D018529:Nutritional Support; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions / Q000627:therapeutic use; D014815:Vitamins / Q000008:administration & dosage*
D000596:Amino Acids; D006571:Heterocyclic Compounds; D007287:Inorganic Chemicals; D012996:Solutions; D014815:Vitamins; D003094:Collagen; D005947:Glucose