The investigation of effects of pentoxifylline and caffeic acid phenethyl ester in treatment D-galactosamine induced acute hepatitis in wistar albino rats

The aim of this study was to investigate histological changes occurred in hepatic tissue and effects of pentoxifylline (PTX) and caffeic acid phenethyl ester (CAPE) on these changes by using histological and biochemical methods in rats, in which hepatitis was established by galactosamine (GAL).In this study, forty-nine Wistar Albino male rats which were provided from Inonu University Laboratory Animals Research Center were used. Rats were divided into 7 groups as follows: Group 1, control group; Group 2, Gal (24) group; Group 3, GAL (continue) group; Group 4, GAL+ PTX group; Group 5, GAL+ CAPE group; Group 6, PTX group; and Group 7, CAPE group. Rats, other than those in Group 2, were sacrified under ketamine/xylazine anesthesia and liver of the rats were removed after 21 days. Right lobe of liver was used for biochemical analysis, whereas left one for histological analysis. Removed tissue samples were appied to routine tissue processes and embedded in paraffin. Histological (Mayer?s Hematoxylin-eosine, PAS, Masson?s trichrome, Toluidine blue) and immunohistochemical (Ki-67 and kaspaz-3) staining methods were applied to sections obtained from paraffin blocks and preparations were examined by using Leica DFC-280 light microscope.In histological evaluations, irregular areas with discrete appearance than normal histological structure were seen in the liver parenchyma of groups treated to galactosamine. These focal areas were comprised of inflammatory, necrotic and apoptotic cells. Glycogen loss was observed in the hepatocytes localized at the periphery of lobule. Mast cells stained to violet were solely observed in portal areas. It was found that number of mast cells in the connective tissue of portal areas were significantly higher in GAL groups compared to other groups (p=0.0001). In addition, number of cells with positive staining by Ki-67 and caspase-3 was significantly increased in GAL groups compared to control group (p=0.0001).In biochemical analyzes, there was an increase in MDA and MPO levels, while a decrease was observed in GSH and GPx activity in groups treated to GAL compared to control group. On the other hand, it was seen that, in the groups treated to GAL, histological and biochemical injuries in the liver were recovered by administration of PTX and CAPE. In these groups, borders of GAL-induced focal areas involving inflammatory, apoptotic and necrotic cells were regressed. Moreover, it was found that numbers of mast cells and caspase-3 positive cells were decreased, while number of Ki-67 positive cells was significantly increases. In the biochemical analysis, MDA and MPO levels were decreased compared to GAL group, while GSH and GPx levels were significantly increased.In this study showed that ameliorative effects of PTX and CAPE on GAL-induced liver injury. In conclusion, we think that the treatment of liver diseases the use of agents with antioxidant and anti-inflammatory properties such as PTX and CAPE have beneficial effects.Key Words: Hepatitis, Galactosamine, Pentoxifylline, CAPE