Study of Potential Anti-inflammatory and Anti-fibrotic Effects of Matthiola arabica Boiss. in an Experimental Model of Liver Fibrosis in Rats

Abstract

The present study was designed to investigate the potential anti-fibrotic effect of glucosinolates hydrolysis products of MatthilaarabicaBoiss., one of the Brassicaceae’s plants which is present in the Egyptian desert. Also, the possible molecular mechanisms underlying this anti-fibrotic activity were elucidated, particularly its effects on fibrosis markers, oxidative stress and inflammatory markers in an experimental model of CCl4- induced liver fibrosis in rats. This was performed throughpreparation of fraction rich in ITCs containing ethyl ITC , 3-butenyl ITC ( napin), 4-(Methylthio)-3-butenyl ITC (dehydroerucin), 4-(Methylsulfinyl) butyl ITC (Sulforaphane), 5-(Methylthio)-4-pentenenitrile (dehydroerucin nitrile) and 5-(Methylthio) pentanenitrile(erucin nitrile) using phytochemical methodsand quantifying the total intact glucosinolates in plant fresh aerial part.To fulfill this goal, the study was divided in two parts: Part I: Screening for the hepatoprotective dose of ITCs in a model of CCl4- induced a cute hepatotoxicity. Thirty animals were randomized into five different groups and treated with either CCl4 (1ml/ kg, once in the seventh day) and/or one of thedifferent doses of ITCs fraction (7.5, 15 and 30mg /kg for six consecutive days) for one week. The following parameters were investigated: 1. Hepatotoxicity indicies: Alanine aminotransferase (ALT) and aspartate aminotransferase(AST). 2. Histopathologicalexamination:Hematoxylin and Eosin (H & E) staining for routine histopathological examination. The findings of part I can be summarized as follows: 1. Serum ALT and AST levels were significantly increased in the CCl4-intoxicated group by 4 and 3folds, respectively as compared to the control group, while pre-treatment of animals with different doses of ITCs fraction showeda significant decrease in the serum ALT and AST levels as compared to CCl4 group, in a dose dependent manner.Indeed, the highest dose (30mg/kg) of ITCs fraction showed the highest hepatoprotection where it decreasedALT and AST serum levels by 61 and51.5%,respectively as compared to CCl4-intoxicated group. Hence, the dose of 30mg/kg of ITCs fraction was selected to be used in the liver fibrosis model.

2. Histopathological examination using Hematoxylin and Eosin (H & E) stain showed extensive hepatocellular damage evidenced by the presence of centrolobular necrosis in diffuse manner all over the hepatocytes, ballooning degeneration, inflammatory infiltration oflymphocytes and fatty changes in most hepatic parenchyma inCCl4-intoxicated group.Interestingly,the pretreated rats with different doses of ITCs fraction revealed that ITCs fraction was able to reduce or even prevent the development of histopatholoogical damage particularly at the high dose (30mg/kg).