HISTOLOGICAL AND IMMUNOHISTOCHEMICAL STUDIES ON HEPATOCARCINOGENESIS INDUCED BY IETHYLNITROSAMINE AND THE PROTECTIVE ROLE OF CURCUMIN IN ALBINO RATS
Samia M. Madbouly and Eman M. El-Mancy
Department of Zoology, Girls college for Arts, Science and Education, Ain Shams University
Hepatocellular carcinoma is a major health problem worldwide and representing the third largest cause of cancer related death. Diethylnitrosamine (DEN), is a potent genotoxic carcinogen that has been shown to induce liver tumours and liver damage upon administration. Carbon tetrachloride (CCl4) is generally not used as a carcinogen, it can be used as a tumour promoter by inducing liver regeneration. Adriamycin(ADR), an antitumour antibiotic, has been found effective against a variety of human cancers. However, with increasing use, it was found to have cardiotoxicity. Curcumin (CCM) is a naturally occurring phytochemical, is potent antioxidant, inhibiting lipid peroxidation, reducing oxidative damage and effectively scavenging superoxide, the hydroxyl radical and nitrogen dioxide. So, this study aimed to investigate the protective effect of curcumin as natural antioxidant against ADR toxicity. In the present study, 65 adult male albino rats were divided into two main groups: control and carcinogenic groups. Control group (20 rats) was divided into negative control and positive control treated with curcumin. The carcinogenic group (carcinogeneted by a single dose i.p of 200 mg/kg/b.w. DEN and CCl4 at a dosage of 1 ml/kg/b.w. twice a week for 10 weeks), was subdivided into 3 groups: the first was the carcinogenic group; the second was treated with only ADR (2.5 mg/kg/b.w. once a week i.p. for 4 weeks), and the third group was treated with ADR and CCM (250 mg/kg/b.w.) daily for 4 weeks. Histological results showed hepatic portal cirrhosis and hepatic arterioles manifested severe branching. The liver tissue also showed well differentiated hepatic neoplasms, as well as poorly differentiated malignant tissue after 16 weeks of treatment with DEN. Cells forming neoplastic mass are pleomorphic, irregular and their nuclei are hyperchromatic. Treatment with ADR only, initiated minor improvement against the carcinogenic agent DEN. The liver tissue showed regression of invasive hepatocellular carcinoma. There was a slight improvement of hepatic lobular architecture. After treatment with ADR and CCM, most hepatocytes markedly retained their normal structure with their small vesicular nuclei and normal chromatin material. It may therefore be concluded that the combined treatment with adriamycin and curcumin had significant beneficial effect on hepatic regeneration, and curcumin as a natural antioxidant exerts more protection against DEN carcinogenesis. Immunohistochemical results showed significant increase in number of proliferating cell nuclear antigen (PCNA) positive cells in DEN-treated group as compared to the control groups. The carcinogenic group which was treated only with adriamycin chemotherapy exhibited minor improvement, while the carcinogenic group, when treated with adriamycin and curcumin, exhibited more improvement of PCNA-positive cells within the hepatocytes.