The protective effects of oleuropein on diethylnitrosamine (den) and phenobarbital (FB) induced liver demage in rats

Canser is the name given to a high mertality rısked disease that some of the body's cells begin to divide without control and spread into vasculer or lymphatic system than to the other sides of body. Genetic and enviramental factors are effective on developing canser. Exposure to factors such as air pollution water pollution or agricultural items are the fist line etiologic factors. Nitrozamines are well known carsinogenic compenents. Diethylnitrosamine (DEN) is one of the nitrozamines that cause hepatic carsinoma, metabolites of DEN helps the covalent binding of the tumor causes to electrons which take role in oxidaxion. Phenobarbital is a nonselective central nervous system depressant which is primarilly used in parsiel or generalized epilepsy. It circulates in the blood as %50 binded to proteins. Number of grups effected the pharmacokinetic of phenobarbital is less than the number of drugs are effected by the phenobarbital effects on cytocrom p450 system phenobarbital increases the metabolism rates of these group of drugs. Oleuropein has important biological properties on olive fruit and its leaves. It has phenolic constituents which have positive effects on huma health. According to the resent studies it has shown that oleuropein has antimicrobial, antiviral and antifungal properties. Oleuropein is nontoxic anticanser substance found in olive it self and it's leaves. Oleuropein surrounds the canser cells irreversibly so prevents their invading and spreading around. In certain doses of oleuropein as medicine prevents mitosis of canser cells. The present study aimed to evaluate if oleuropein has a preventive effect on liver injury in rats which has been given diethylnitrosamine (DEN), phenobarbital (PB) In this study 50 Sprague-Dawley type male rats which are 220±20 gr weight are used. They are divided in to 5 groups as control group, diethylnitrosamine (DEN) group, diethylnitrosamine (DEN)+ phenobarbital (PB) group, diethylnitrosamine (DEN)+phenobarbital (PB)+oleuropein (OLE) group and oleuropein (OLE) group. At the end of the study all rats are given 75 mg/kg ketamine and 10 mg/kg xylazine intraperitoneally and they are decapited. At the end of the 8 week of the study blood and liver samples of the decapited rats are taken. In these samples malondialdehyde (MDA), catalase (CAT), süperoxide dismutase (SOD), glutathione(GSH) levels are studied and histological changes are examined. Although there was a significant difference among the groups in terms of liver GSH and MDA levels and CAT activities, there was no significant difference among the groups in SOD activity. There was a significant decrease in liver GSH levels in the DEN and DEN+PB groups compared to the control group while there was no statistically significant difference between the OLE, and DEN+PB+OLE groups and the control group. In terms of CAT activity of the liver, a significant decrease was observed in the OLE group compared to the DEN, DEN+PB, DEN+PB+OLE groups. DEN+PB group liver MDA levels were significantly lower than DEN+PB+OLE group liver MDA levels. There was no difference among groups in terms of liver SOD levels. The application of DEN separately and with PB, and OLE for treatment resulted in a statistically significant difference in blood MDA, GSH levels, and CAT, SOD activities. There was a statistically significant increase in blood MDA levels of the DEN+PB group compared to the control. OLE treatment caused a significant reduction in OLE group MDA levels compared to those of control, just as MDA levels of DEN+PB+OLE group compared to those of DEN+PB group. Blood CAT activity indicated a significant increase in the OLE group compared to the DEN+PB group. Moreover, it showed a significant increase in DEN+PB+OLE group compared to the those of DEN+PB group. Upon blood GSH levels were compared, there was no statistically significant difference between the DEN+PB+OLE group and the control group, while DEN and DEN+PB groups showed a significant decrease compared to the control group. GSH levels in the OLE group were significantly higher than those of control. There was no difference in the blood SOD levels of OLE and DEN+PB+OLE groups compared to the control whereas these levels significantly decreased in the DEN+PB group compared to the control group. In conclusion we can say that oxidative stress has an important role on liver carsinogenesis and there is a relationship between hepatocarsinogenesis and lipid peroxidaxion. CAT has an important role on cell damage because of it's function of translating H2O2 to harmless products. It seems application of oleuropein in significant dosage and time period has protective effects against oxidative stress on rat blood and liver parameters, during liver damage period. But there is need for further studies about oleuropein for treatment options of damage.