PMID- 19944210 OWN - NLM STAT- MEDLINE DCOM- 20100203 LR - 20131121 IS - 1531-5037 (Electronic) IS - 0022-3468 (Linking) VI - 44 IP - 11 DP - 2009 Nov TI - Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction-an experimental study in growing animals. PG - 2071-7 LID - 10.1016/j.jpedsurg.2009.05.020 [doi] AB - 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. FAU - Andrade, Wagner de Castro AU - Andrade Wde C AD - Pediatric Surgery Division, Laboratory of Pediatric Surgery, University of Sao Paulo Medical School, CEP 01246-903 Sao Paulo, Brazil. FAU - Tannuri, Uenis AU - Tannuri U FAU - da Silva, Luiz Fernando Ferraz AU - da Silva LF FAU - Alves, Venancio Avancini Ferreira AU - Alves VA LA - eng PT - Journal Article PL - United States TA - J Pediatr Surg JT - Journal of pediatric surgery JID - 0052631 RN - 0 (Glucocorticoids) RN - 0 (Phosphodiesterase Inhibitors) RN - 9PHQ9Y1OLM (Prednisolone) RN - SD6QCT3TSU (Pentoxifylline) SB - IM MH - Animals MH - Biliary Atresia/complications/drug therapy MH - Biliary Tract Diseases/congenital MH - Cholestasis/complications/*prevention & control MH - Common Bile Duct Diseases/complications/prevention & control MH - Disease Models, Animal MH - Drug Therapy, Combination MH - Glucocorticoids/*pharmacology/therapeutic use MH - Humans MH - Hypertension, Portal/*drug therapy MH - Ligation MH - Liver Cirrhosis, Experimental/etiology/*prevention & control MH - Pentoxifylline/*pharmacology/therapeutic use MH - Phosphodiesterase Inhibitors/*pharmacology/therapeutic use MH - Prednisolone/*pharmacology/therapeutic use MH - Rats MH - Rats, Wistar MH - Weight Gain/drug effects EDAT- 2009/12/01 06:00 MHDA- 2010/02/04 06:00 CRDT- 2009/12/01 06:00 PHST- 2009/02/24 00:00 [received] PHST- 2009/05/10 00:00 [revised] PHST- 2009/05/11 00:00 [accepted] PHST- 2009/12/01 06:00 [entrez] PHST- 2009/12/01 06:00 [pubmed] PHST- 2010/02/04 06:00 [medline] AID - S0022-3468(09)00414-X [pii] AID - 10.1016/j.jpedsurg.2009.05.020 [doi] PST - ppublish SO - J Pediatr Surg. 2009 Nov;44(11):2071-7. doi: 10.1016/j.jpedsurg.2009.05.020.