Investigation of antitumor efficacy of urtica dioica in experimentally diethylnitrosamine-induced hepatocellular carcinogenesis process in rats

Cancer is the second commonest cause of death a disease that causes after cardiovascular system diseases the most death. A large part of the primary malignant tumors of the liver is hepatocellular carcinoma. Diethylnitrosamine (DEN) constitutes a large part of genetically effective chemical carcinogens. DEN is found in cigarette smoke, cured and fried foods, cosmetic products, alcoholic beverages, processed meat products, chemicals used in agriculture and various industrial products. DEN are metabolized in the liver and have carcinogenic, teratogenic, toxic and mutagenic effects. DEN is widely used as an inducer for tumor formation of the liver in experimental animals. It is known that stinging nettle (Urtica dioica) which is widely used in alternative medicine today, has many medicinal properties such as anticanccinogenic, anti-inflammatory, antimicrobial, antitoxic, antioxidant, hepatoprotective, antidiabetic and hypoglycemic. In the present study, the antitumor activity of Urtica dioica was investigated in the process of hepatocellular carcinogenesis induced by diethylnitrosamine in rats. For this purpose; 40 rats in total were divided into 5 groups of 8 each. The control group was fed with normal rat food. UDS group rats were given 1 ml of UDS extract (0.5 ml ether oil extract and 0.5 ml ethanol extract) orogastrically daily for 16 weeks. DEN group were given 200 mg/kg DEN once intraperitoneally. DEN+UDSE-1 group were given 200 mg/kg DEN once intraperitoneally and 1 ml of UDS ethanol extract orogastrically daily for 16 weeks. DEN+UDSE-2 group were given 200 mg/kg DEN once intraperitoneally and 1 ml of UDS ether oil extract orogastrically daily for 16 weeks. At the end of the 16 weeks trial, samples were taken from the necropsied rats for biochemical and histopathological analysis. Biochemically; DEN application caused the levels of TOS and MDA, the activities of AST, ALT and LDH to increas, but the levels of TAS, GSH, CAT, SOD and GSH-Px to decrease. However, it was observed that the use of UDSE together with DEN increased antioxidant capacity, suppressed oxidative stress and prevented liver damage. On the other hand, it was determined that DEN administration significantly increased levels of tumor markers CA 15-3, CA 19-9 and CA 125-II activities, especially caspase-3 levels and the use of UDSE together with DEN reverses these increases. Pathologically, in the DEN group, there was a fine granular appearance on the surface of the livers. Histopathologically, the dysplasias in the form of large and small cell changes were commonly observed in hepatocytes. Additionally, bile duct hyperplasia, inflammatory cell infiltrations, fibrosis and cholestasis were seen in the liver parenchyma. In the groups receiving UDSE with DEN, dysplastic large cell changes, cystic degenative hepatocytes and fibrosis were not observed, however the other pathological changes were at mild levels. Immunohistochemically, in the DEN group, there was a significant retraction in Hep par-1, AFP, caspase-3 and iNOS staining, while in the groups receiving UDTE with DEN, there was a significant decrease in the expression of these antibodies. According to these results, in the process of hepatocellular carcinogenesis induced by diethylnitrosamine, it was concluded that UDS extract has a very significant antitumor activity by preventing tissue damage due to its strong antioxidant capacity.