Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction in growing animals: immunohistochemical analysis of the expression of TGF- β and VEGF

Abstract

OBJECTIVE:During the neonatal and infancy periods, some chronic liver diseases may lead to progressive hepatic fibrosis, which is a condition that can ultimately result in the loss of organ function and severe portal hypertension necessitating hepatic transplantation. In a previous report, pharmacological interventions were demonstrated to modulate hepatic fibrosis induced by bile duct ligation in young rats. The administration of pentoxifylline or prednisolone, or the combination of both, resulted in reduced fibrogenesis in portal spaces. The objectives of the present study were to evaluate the expression of transforming growth factor β and vascular endothelial growth factor after bile duct ligation in young rats and to assess the effect of those same drugs on cytokine expression.METHODS:In this experimental study, 80 young rats (21 or 22 days old) were submitted either to laparotomy and common bile duct ligation or to sham surgery. The animals were allocated into four groups according to surgical procedure, and the following treatments were administered: (1) common bile duct ligation + distilled water, (2) sham surgery + distilled water, (3) common bile duct ligation + pentoxifylline, or (4) common bile duct ligation + prednisolone. After 30 days, a hepatic fragment was collected from each animal for immunohistochemical analysis using monoclonal antibodies against transforming growth factor β and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed.RESULTS:The administration of pentoxifylline reduced the transforming growth factor β-marked area and the amount of transforming growth factor β expressed in liver tissue. This effect was not observed after the administration of prednisolone. There was a significant reduction in vascular endothelial growth factor expression after the administration of either drug compared with the non-treatment group.CONCLUSIONS:The administration of pentoxifylline to cholestatic young rats resulted in the diminished expression of transforming growth factor β and vascular endothelial growth factor in liver tissue. The administration of steroids resulted in the diminished expression of vascular endothelial growth factor only. These pathways may be involved in hepatic fibrogenesis in young rats submitted to bile duct ligation and exposed to pentoxifylline or prednisolone.

Pentoxifylline and Methylprednisolone Additively Alleviate Kidney Failure and Prolong Survival of Rats after Renal Warm Ischemia-Reperfusion

“…In another study, added to dexamethasone, it enhanced the alleviation of an induced limb ischemia in rat by 2-fold [ 27 ]. In the rat model of biliary obstruction, treatment with PTX or/and prednisolone for 30 days resulted in reduced portal fibrosis, however with no additive effect of the drug combination [ 28 ]. The clinical setting where the effects of PTX were repeatedly confronted with those of steroids was alcoholic hepatitis.…”

Efficacy and Safety of Pentoxifylline on Patients with Non-Alcoholic Steatohepatitis; Randomized Controlled Trial

“…Also, PTX inhibits several pro-in ammatory cytokines such as TNF-α [21,22]. Previous studies reported that the anti brogenic effects of PTX have been suggested by several studies [23,24]. Therefore, we intended to appraise the e cacy of PTX on NASH patients for 6 months in comparison with NASH patients who received regular treatment through evaluation of anthropometric, hematological, hepatic function, lipid pro le parameters, and non-invasive hepatic brosis score regarding active fatty (FLI), aspartate aminotransferase to platelet ratio (APRI) index, brosis-4 (FIB-4) index, NAFLD brosis score (NFS).…”