Protection Against Diethylnitrosamine Induced Hepatocarcinogenesis by Nigella SativaIn Rats

This investigation has been conducted to study the protective effect of water extract of Nigella sativa (NS) against Diethylnitrosamine (DEN) induced hepatocarcinogenesis in rats. Seventy five Wistar rats, divided into five equal groups, were used. Group A rats were dosed with DEN (200 mg/ kg) intra-peritoneally; 12 hours later the rats were given NS water extract orally at a dose of 6 g/ kg/ day for 8 weeks. Group B rats were injected with DEN only and stayed for 8 weeks (positive control). Group C rats received NS extract daily per os for 8 weeks (negative control). Group D rats were dosed with DEN and after 6 weeks they received NS extract daily for another 6 weeks. Group E rats were administered with NS extract daily for 6 weeks, then dosed with DEN, and kept for 6 weeks. The experimental rats were subjected to partial hepatectomy (PH) two weeks after the administration of DEN, except those of group C in which PHwas done two weeks after the administration of NS extract. All rats were euthanized at the end of the experiments and postmortem examination was carried out. Sample from livers and lungs were taken in 10% neutral formaline for histopathology and immunohistochemistry. The results of liver histopathology in all groups revealed the presence of degenerative changes in the form of hepatocyte cytoplasmic vacuolations. These were mild to moderate in groups A, D & E but marked in group B rats. In the negative control group (C) the changes were minimal.Cell dysplasia, seen as cellular pleomorphism, nuclear hyperchromacia, presence of binucleate and multinucleate cell, was observed in all groups receiving DEN; these changes were more obvious in group B and are considered as premalignancy changes. No necrotic or inflammatory alterations were noticed. Immunohistochemistry was done to identify the Glutathione-S Transpherase Placental form (GST-P) positive foci, as tumor marker, in all liver sections using the avidin-biotin complex method. There was a significant decrease in the number of positive foci of GST-P in liver sections of the test groups particularly groups Aand Ewhen compared with group Breceiving only DEN. It was concluded that NS water extract could have a protective effect against DEN-mediated hepatocarcinogenesis in rats if given within few hours after DEN injection or 6week before injection of DE