Role of LTB4 and nitric oxide in the gastroprotective effect of Prosthechea karwinskii leaves extract in the indomethacin-induced gastric injury in the rat.

Gastric injury is mainly described by inflammation of the gastric epithelium. Recently, our group of work demonstrated that Prosthechea karwinskii leaves extract induces both an in vitro antioxidative action and an in vivo gastroprotective effect in a rat. However, the molecules involved in the gastroprotective action by Prosthechea karwinskii are not known. Thus, the aim of this study is to determine whether Prosthechea karwinskii extract modifies anti-inflammatory and antioxidative biomarkers in an in vivo rat model of indomethacin-induced gastric injury. Rats were orally administered with indomethacin and Prosthechea karwinskii leaf extract. Our results suggest that the gastroprotective effect of Prosthechea karwinskii leaf extract is related to the reduction in leukocyte infiltration and antioxidative action in a model of indomethacin-induced gastric injury. Further studies are warranted to investigate the role of the compounds identified in the gastroprotective action of Prosthechea karwinskii leaves extract.

Coffee consumption prevents fibrosis in a rat model that mimics secondary biliary cirrhosis in humans.

Investigations demonstrated that oxidative stress plays an important role in injury promotion in cholestatic liver disease. We hypothesized that coffee attenuates cholestasis-induced hepatic necrosis and fibrosis via its antioxidant, anti-inflammatory, and antifibrotic properties. The major aim of this study was to evaluate the hepatoprotective properties of coffee and caffeine in a model of chronic bile duct ligation (BDL) in male Wistar rats. Liver injury was induced by 28-day BDL, and conventional coffee, decaffeinated coffee, or caffeine was administered daily. After treatment, the hepatic oxidative status was estimated by measuring lipid peroxidation, the reduced to oxidized glutathione ratio, and glutathione peroxidase. Fibrosis was assessed by measuring the liver hydroxyproline content. The transforming growth factor-ß, connective tissue growth factor, α-smooth muscle actin, collagen 1, and interleukin-10 proteins and mRNAs were measured by Western blot and polymerase chain reaction, respectively. Conventional coffee suppressed most of the changes produced by BDL; however, caffeine showed better antifibrotic effects. Coffee demonstrated antioxidant properties by restoring the redox equilibrium, and it also prevented the elevation of liver enzymes as well as hepatic glycogen depletion. Interestingly, coffee and caffeine administration prevented collagen increases. Western blot assays showed decreased expression levels of transforming growth factor-ß, connective tissue growth factor, α-smooth muscle actin, and collagen 1 in the coffee- and caffeine-treated BDL groups. Similarly, coffee decreased the mRNA levels of these proteins. We conclude that coffee prevents liver cirrhosis induced by BDL by attenuating the oxidant processes, blocking hepatic stellate cell activation, and downregulating the main profibrotic molecules involved in extracellular matrix deposition.

Antifibrotic and antioxidant effects of N-acetylcysteine in an experimental cholestatic model.

OBJECTIVES: Several studies have suggested that oxidative stress may play an important role in the pathogenesis of hepatic injury during cholestasis in rats and humans. The aim of this study was to evaluate the ability of N-acetylcysteine (NAC) to prevent the damage induced by bile duct ligation (BDL) for 28 days in male Wistar rats. METHODS: NAC was administered daily (300 mg/kg, orally) for 28 days. Alanine aminotransferase was quantified in the serum; lipid peroxidation, glutathione, and catalase activity were measured in the liver. Fibrosis was assessed by measuring the liver hydroxyproline content; transforming growth factor-ß (TGF-ß), interleukin (IL)-6, and IL-10 were determined in the liver by a western blot and quantified densitometrically. RESULTS: The induction of cholestatic damage by BDL was associated with an increase in alanine aminotransferase. Oxidative stress was also evaluated; lipid peroxidation increased, whereas the liver glutathione content and catalase activity decreased by BDL. NAC treatment prevented these alterations. Hydroxyproline was increased by chronic BDL, but NAC preserved the normal hydroxyproline levels. Cytokines TGF-ß, IL-6, and IL-10 increased after 28 days of BDL. NAC was effectively significant in preventing TGF-ß and IL-6 expression and further augmented the IL-10 expression. CONCLUSION: Our data indicate that in the development to cholestatic liver damage, oxidative stress plays an important role and this in turn leads to fibrosis. This study shows that the beneficial effects of NAC are because of its antioxidant and immunomodulatory properties.

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