Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction-an experimental study in growing animals.
BACKGROUND
Many chronic liver diseases lead to progressive hepatic fibrosis, a condition that can ultimately result in loss of organ function and severe portal hypertension necessitating hepatic transplantation. Within the last few decades, studies have been conducted to demonstrate the possibility of drug modulation of hepatic fibrogenesis. Regarding biliary obstruction, it has been suggested that administration of corticosteroids could promote better late outcomes for children with biliary atresia submitted to Kasai's portoenterostomy. Models used to test potential antifibrogenic drugs such as pentoxifylline (PTX) have not included growing animals.


METHODS
In this experimental study, 119 young rats (21st or 22nd days) were submitted to laparotomy and common bile duct ligation (CBDL) or to sham surgery (SHAM). Animals were allocated into 5 groups, according to surgical procedure, and administered the following solutions: (1) CBDL + distilled water, (2) SHAM + distilled water, (3) CBDL + PTX, (4) CBDL + prednisolone (PRED), and (5) CBDL + PTX + PRED (PTX + PRED). Each group was further divided into 2 subgroups according to the length of the experiment (15 or 30 days). At the end of the defined period, animals were weighed, and a hepatic fragment was collected from each one for analyses.


RESULTS
The PTX animals exhibited increased weight gain compared to animals in the PRED or PTX + PRED groups. Animals from the 3 therapeutic groups (PTX, PRED, and PTX + PRED) showed diminished collagen-filled area in portal spaces. Total portal space area was increased in the PTX group.


CONCLUSIONS
Hepatic fibrosis induced by bile duct ligation in young rats could be modulated by pharmacologic interventions. Administration of PTX or PRED, or the combination of both, resulted in diminished collagen-filled areas in portal spaces.
Andrade
Wagner de Castro
Wde C
Pediatric Surgery Division, Laboratory of Pediatric Surgery, University of Sao Paulo Medical School, CEP 01246-903 Sao Paulo, Brazil.
Tannuri
Uenis
U
da Silva
Luiz Fernando Ferraz
LF
Alves
Venancio Avancini Ferreira
VA
D000818:Animals; D001656:Biliary Atresia / Q000150:complications / Q000188:drug therapy; D001660:Biliary Tract Diseases / Q000151:congenital; D002779:Cholestasis / Q000150:complications / Q000517:prevention & control*; D003137:Common Bile Duct Diseases / Q000150:complications / Q000517:prevention & control; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy*; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000517:prevention & control*; D010431:Pentoxifylline / Q000494:pharmacology* / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011239:Prednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects
D005938:Glucocorticoids; D010726:Phosphodiesterase Inhibitors; D011239:Prednisolone; D010431:Pentoxifylline