Therapeutic Efficacy of Allyl Isothiocyanate Evaluated on N-Nitrosodiethylamine/Phenobarbitol induced Hepatocarcinogenesis in Wistar Rats

  • G. Thiyagarajan Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai-600 020, India.
  • A. S. Gowtham Kumar Genetics Division, Central Research Laboratory, Chettinad University, Kelambakkam, Chennai-603103, India.
  • V. Ramakrishnan Department of Pharmacology, Chettinad University, Kelambakkam, Chennai-603103, India.
  • N. Madhusudhanan Department of Pharmacology, Sri Manakula Vinayagar Medical College and Hospital, Pondicherry-605107, India.
  • C. Anbu Selvam Department of Pharmacology and Environmental Toxicology, Dr. A.L.M.P.G.I.B.M.S, University of Madras, Taramani, Chennai-600113, India.
Keywords: Hepatocarcinogenesis, Allyl isothiocyanate, Antioxidants, Marker enzymes, Alfa-fetoprotein


N-nitrosodiethylamine (NDEA) is a potential carcinogenic agent that induces liver cancer. To evaluate the chemotherapeutic effect of Allyl isothiocyanate in the experimental model, Wistar male rats were administered single dose of intraperitoneal (IP) injection of NDEA. Two weeks after administration of NDEA, Phenobarbital at the concentration of 0.05% was incorporated in rat chow for up to 14 successive weeks to promote liver cancer. Allyl isothiocyanate (AITC) (2mg/kg body weight) in addition with 0.5ml of corn oil was given orally on a daily basis. At the end of this experimental period, the rats were sacrificed and the blood samples were taken for biochemical studies. The levels of the marker enzymes for liver function were measured in serum. The results of the biochemical studies showed that NDEA administration followed by phenobarbital induces macro and microscopic liver tumors that increase the levels of marker enzymes and decreases the level of antioxidant in the serum in addition to loss of body weight. Conclusively, the administration of AITC as therapeutic treatment for hepatocarcinoma has significantly reduced the tumor development and counteracted all the biochemical effects induced by NDEA.


Download data is not yet available.


[1]. IARC. N-nitrosodiethanolamine (2000). IARC Monogr. Eval. Carcinog. Risks Hum. 77: 403–438.
[2]. Loeppky, R.N. (1999). The mechanism of bioactivation of N-nitrosodiethanolamine. Drug Meta. Rev., 31:175–193.
[3]. Fahey, Zhang & Talalay (1997). Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc. Natl. Acad. Sci. USA, 94: 10367–10372.
[4]. Uematsu, Hirata, Suzuki, Ilda, Ueta & Kamata (2002). Determination of isothiocyanates and related compounds in mustard and horseradish extract used as natural food additives. Shokuhin Eiseigaku Zassihi, 43:10–17.
[5]. Chung, Morse, Eklind & Lewis (1992). Quantitation of human uptake of the anticarcinogen phenethyl isothiocyanate after a watercress meal. Cancer Epidemiol. Biomark. Prev., 1: 383–388.
[6]. Zhang, Talalay, Cho & Posner (1992). A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc. Natl. Acad. Sci., USA, 89: 2399–2403.
[7]. Akhilesh Kumar, Saritha S. D’Souza, Sanjay Tickoo, Bharathi P, Salimath & Singh (2009) Antiangiogenic and proapoptotic activities of Allyl isothiocyanate inhibit ascites tumor growth in-vivo. Integ. Cancer Therap., 8 (1): 75-87.
[8]. Hisashi Matsuda, Momotaro Ochi, Akifumi Nagatomo & Masayuki Yoshikawa (2007). Effects of allyl isothiocyanate from horseradish on several experimental gastric lesions in rats. Europ. J. of Pharmacology, 561:172–181.
[9]. King, J. (1965a). The phosphohydrolysases-acid and alkaline phosphatase. In: Practical Clinical Enzymology. Ed. by Van D. Nostrand Co. Ltd, London. 191-208.
[10]. Balasubramanian, M.P., Dhandaythapani, S., Nellaiyappan, K. & Ramalingam, K. (1983) Comparative studies on phosphomonoesterase in helminths. Helminthologia, 20: 111-120.
[11]. King, J. (1965b). The Transferases – alanine and aspartate transaminases. In: Practical and Clinical Enzymology. Van Nostrand Co. Ltd., London. Pp.121-138.
[12]. Marklund, S. & Marklund, G. (1974). Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Ero. J. Biochem., 47: 469-474.
[13]. Sinha, A.K. (1972). Colorimetric assay of catalase. Anal. Biochem., 47: 389 394.
[14]. Rotruck, Pope, Ganther, Swanson, Hafeman & Hoekstra (1973). Selenium: biochemical role as a component of glutathione peroxidase. Science, 179: 588-590.
[15]. Muzio, G., Marengo, B., Salvo, R. et al., (1999). Liver cancer is induced by a subnecrogenic dose of NDEA when associated with fasting/refeeding: role of glutathione-transferase and lipid peroxidation. Free Radic. Biol. Med., 26:1314–1320.
[16]. Bansal, A.K., Trivedi, R., Soni, G.L. & Bhatnagar, D. (2000). Hepatic and renal oxidative stress in acute toxicity of N-nitrosodiethylamine in rats. Indian J. Exp. Biol., 38:916– 920.
[17]. Tameda, M., Shiraki, K., Ooi, K. et al. (2005). Aspartate aminotransferase- immunoglobulin complexes in patients with chronic liver disease. World J. Gastroenterol., 11:1529–1531.
[18]. Sreepriya, M. & Bali, G. (2005). Chemopreventive effects of embelin and curcumin against N-nitrosodiethylamine/ Phenobarbital induced hepatocarcinogenesis in Wistar rats. Fitoterapia, 76: 549–555.
[19]. Yuen, M.F. & Lai, C.L. (2005). Serological markers of liver cancer. Best Pract. Res. Clin. Gastroenterol., 19: 91–99.
[20]. Karbownik, M., Lewinski, A. & Reiter, R.J. (2001). Anticarcinogenic actions of melatonin which involve antioxidative processes: comparison with other antioxidants. Int. J. Biochem. Cell Biol., 33: 735–753.
[21]. Canuto, R.A., Muzio, G., Biocca, M.E. & Dianzani, M.U. (1991). Lipid peroxidation in rat AH-130 hepatoma cells enriched in vitro with arachidonic acid. Cancer Res., 51: 4603–4608.
[22]. Burdon R.H. (1995). Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radic. Biol. Med., 18:775–794.
[23]. Huang, Z.Z., Chen, C., Zeng, Z. et al., (2001). Mechanism and significance of increased glutathione level in human hepatocellular carcinoma and liver regeneration. FASEB J., 15:19–21.
[24]. Senturker, S., Karahalil, B., Inal, M. et al., (1997). Oxidative DNA base damage and antioxidant enzyme levels in childhood acute lymphoblastic leukemia. FEBS Lett., 416:286–290.
[25]. Safford, S.E., Oberley, T.D., Urano, M. & St Clair, D.K. (1994). Suppression of fibrosarcoma metastasis by elevated expression of manganese superoxide dismutase. Cancer Res., 54: 4261– 4265.
[26]. Antolin, I., Rodriguez, C., Sainz, R.M et al., (1996). Neurohormone melatonin prevents cell damage: effect on gene expression for antioxidant enzymes. FASEB J., 10: 882–890.
[27]. Bansal, A.K., Bansal, M., Soni, G. & Bhatnagar, D. (2005). The protective role of vitamin E pre-treatment on Nnitrosodiethylamine induced oxidative stress in rat liver. Chem. Biol. Interact., 156:101–111.
[28]. Cameron, R.G., Armstrong, D., Gunsekara, A., Varghese, G. & Speisky, H. (1991). Utilization of circulating glutathione by nodular and cancerous intact rat liver. Carcinogenesis, 12: 2369– 2372.
How to Cite
Thiyagarajan, G., Gowtham Kumar, A., Ramakrishnan, V., Madhusudhanan, N., & Selvam, C. (2010). Therapeutic Efficacy of Allyl Isothiocyanate Evaluated on N-Nitrosodiethylamine/Phenobarbitol induced Hepatocarcinogenesis in Wistar Rats. Journal of Advanced Laboratory Research in Biology, 1(1), 5-9. Retrieved from