The role of oxymatrine in regulating TGF-ß1 in rats with hepatic fibrosis

Abstract Purpose: To investigate whether oxymatrine (OMT) prevents hepatic fibrosis in rats by regulating liver transforming growth factor β1 (TGF-β1) level. Methods: Hepatic fibrosis was induced in rats by thioacetamide (TAA). Blood was collected at the end of week 12 to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutathione (GSH). Changes in liver tissue were observed after hematoxylin-eosin (HE) staining. Results: Fibrosis was confirmed by Masson's collagen staining. Liver TGF-β1 level was determined by ELISA. OMT significantly reduced serum ALT and AST but increased GSH levels in rats with hepatic fibrosis. Moreover, it significantly improved liver histology in rats with TAA-induced hepatic fibrosis. It significantly decreased liver TGF-β1 level compared to that in the untreated group. It also significantly reduced collagen deposition in rats. Conclusion: Oxymatrine is effective in protecting rats from thioacetamide-induced hepatic fibrosis by regulating TGF-β1 expression.

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

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.

Capillaria hepatica-induced septal fibrosis in rats: a contribution to the study of liver fibrogenesis / Contribuição para o estudo da fibrogenesis hepática em ratos infectados com Capillaria hepatica

INTRODUCTION: Septal fibrosis of the liver regularly develops in rats infected with the nematode Capillaria hepatica. Curative treatment of the infection prevents the development of septal fibrosis when intervention occurs up to postinfection day (PID) 15, but not later. The present investigation aimed to demonstrate which parasitic factors are present when the process of septal fibrosis can no longer be prevented by curative treatment. METHODS: Wistar rats were infected with 600 embryonated eggs of C. hepatica administered by gavage and treated with ivermectin and mebendazole in separate groups at PIDs 10, 12, 15, 17 or 20. Rats from each group and their nontreated controls, were killed and examined 40 days after the end of treatment. RESULTS: Findings by PID 15 were compatible with the stage of complete maturation of infection, when worms and eggs were fully developed and a complex host-parasite multifocal necroinflammatory reaction showed greater intensity, but with no signs of septal fibrosis, which appeared from PID 17 onward. CONCLUSIONS: Since the worms spontaneously died by PID 15, not only septal fibrosis production, but also its maintenance and further development appeared dependent on the presence of eggs, which were the only parasitic factor remaining thereafter.

INTRODUÇÃO: A fibrose septal do fígado se desenvolve regularmente em ratos infectados pelo nematódeo Capillaria hepatica. O tratamento curativo da infecção, feito antes do 15º dia da infecção, mas não mais tarde, impediu o aparecimento da fibrose septal. O presente trabalho procura verificar qual o estado do parasitismo aos 15 dias da infecção, crucial para patogenia da fibrose septal. MÉTODOS: Ratos foram infectados por via digestiva com 600 ovos embrionados de C. hepatica e tratados com Ivermectina e mebendazol, em grupos separados, aos 10, 12, 15, 17 ou 20 dias após a infecção. O animal de cada grupo e seus respectivos controles foram mortos e examinados aos 40 dias após o fim do tratamento. RESULTADOS: Os achados aos 15 dias da infecção mostraram a maturação completa da parasitose, com presença de ovos e vermes, circundados por reação necro-inflamatória, mas ainda sem fibrose septal. Daí por diante, a fibrose septal se fez presente. CONCLUSÕES: Como os vermes morrem espontaneamente após o 15º dia da infecção, não apenas a origem, mas o posterior crescimento e a manutenção da fibrose septal dependem da presença dos ovos acumulados no fígado, os quais são os únicos elementos parasitários presentes após o 15º dia da infecção por C. hepatica no rato.

Comparative effects of colchicine and silymarin on CCI4-chronic liver damage in rats

The comparative effects of colchicine (10 µg day-1, p.o.) and silymarin (50 mg kg-1, p.o.) each given for 5 days a week on the chronica carbon tetrachloride (CCl4) liver damage were studied. Treatment with CCl4, resulted in a marked reduction of Na+, K+, and Ca2+-ATPases in plasma liver membranes as compared to vehicles or either silymain or chochicine alone. Collagen content in livers of animals treated with CCl4 was increased about four-folds as compared to controls and histological examination of liver samples showed thad collagen incfrease distorted the normal liver architecture. Colchicine or silymarin treatment completely prevented all the changes observed in CCl4-cirrhotic rats (namely, lipid peroxidation, Na+, k+ and Ca2+-ATPases), except for livel collagen conten which was reduced only 55 percent as compared with CCl4-treated rats and for alkaline phosphatase and glutamic pyruvic transminase wich still remained above controls. In the CCl4 + silymarin group, the loss of glycogen content was completely prevented. However, when rats were treated with CCl4+colchicine, liver glycogen content could not be restored. The hepatoprotective effects of colchicine or silymarin were very similar in regard to the prevention of chronic liver damage