CHEMOPREVENTIVE POTENTIAL OF DIPHENYLMETHYL SELENOCYANATE 527 Copyright © 2007 John Wiley & Sons, Ltd. J. Appl. Toxicol. 2007; 27: 527–537 DOI: 10.1002/jat JOURNAL OF APPLIED TOXICOLOGY J. Appl. Toxicol. 2007; 27: 527–537 Published online 9 March 2007 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/jat.1230 Protective effect of diphenylmethyl selenocyanate against CCl 4 -induced hepatic injury Rajat Kumar Das, Sk. Ugir Hossain and Sudin Bhattacharya Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India Received 6 June 2006; Revised 28 November 2006; Accepted 26 December 2006 ABSTRACT: Organoselenocyanates represent an important class of chemopreventive agent, which possess antioxidative, antimutagenic as well as cancer chemopreventive properties. The present study is an attempt to evaluate the protective effect of diphenylmethyl selenocyanate — a synthetic organoselenocyanate against carbon tetrachloride (CCl 4 )-induced hepatic damage in Swiss albino mice in vivo. Mice were pretreated with the Se-compound orally in a duration dependent manner (7 and 15 days) to observe its protective action against an acute toxic dose (24 h) of CCl 4 (single injection at a dose of 20 μl and 50 μl kg -1 b.w.) that induced hepatic necrosis and caused DNA damage (strand breaks) in the hepatocytes. This study revealed that pretreatment with the Se-compound reduced the extent of massive hepatic necrosis in a duration dependent manner, but it had no modulatory effect on hepatocellular apoptosis caused by acute toxic doses of CCl 4 . It was also found that the Se-compound could significantly (P < 0.01) prevent the CCl 4 -induced elevation of DNA damage in hepatocytes measured by comet assay in a duration dependent manner. So these findings will further strengthen the view that organoselenocyanate is an effective chemopreventive agent against acute hepatic damage, caused by halogenated alkanes such as CCl 4 . Copyright © 2007 John Wiley & Sons, Ltd. KEY WORDS: organoselenocyanates; diphenylmethyl selenocyanate; carbon tetrachloride (CCl 4 ); CCl 4 induced liver necrosis; CCl 4 induced liver apoptosis; CCl 4 induced DNA damage; comet assay * Correspondence to: Dr Sudin Bhattacharya, Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, India. E-mail: sudinb1957@yahoo.co.in Introduction Hepatic injury induced by halogenated alkanes has been recognized as one of the most common toxicological problems (Weber et al., 2003). Carbon tetrachloride (CCl 4 ) is one of the chlorinated hydrocarbons that have a widespread use in various industries as a solvent. It is also used in medicine as a vermifuge in the treatment of hookworm disease. On the other hand, exposure to CCl 4 by inhalation, ingestion or absorption through the skin resulted in many cases of poisoning. CCl 4 is a potent hepatotoxin in a variety of experimental animal models (Weber et al., 2003), and induces necrosis (Sivikova et al., 2001) and apoptosis (Jialan et al., 1998) in the liver. Prolonged administration of CCl 4 leads to fibrosis, cirrhosis and hepatic carcinoma (Wernke and Schnell, 2004). The increasing amount of information in recent years on the role of reactive oxygen species in pathology has brought new ideas for the therapy of a variety of diseases. Several reports have appeared describing the antioxidant activity of organoselenium compounds (Nogueira et al., 2004; Meotti et al., 2004) in different experimental models. In fact, selenium (Se) is an essen- tial trace element required for animals and humans for its possible role as a potent antioxidant against oxidative stress induced by xenobiotic compounds of diverse nature (Ozardali et al., 2004) protecting cell membranes from free radical damage (Olivieri et al., 1996). Selenium is involved in maintaining normal liver function, protein synthesis and protects against toxic minerals such as arsenic, cadmium, mercury and lead. Studies suggest that low selenium status may increase the risk of oxidative damage and cancer (Rayman, 2000). It was reported in the literature that different forms of Se-compounds have a hepatoprotective role against CCl 4 induced hepato- cellular damage in various animal model systems (Ianas et al., 1995; Wasser et al., 2001; Atkinson et al., 2001; Zhang et al., 1996). It has been revealed that organic selenium is more efficiently absorbed in the body (Garcia, 2004) and is less toxic than inorganic Se- compounds (Ganther, 1987; Wu et al., 1995). Efforts are under way to develop suitable organoselenium com- pounds with least toxicity and better antioxidant efficacy. Diphenylmethyl selenocyanate, a synthetic organo- selenium compound, was reported earlier as a potential cancer chemopreventive agent against chemically induced carcinogenesis (Ghosh et al., 2005a, 2005b; Das and Bhattacharya, 2004, 2005; Das et al., 2004b, 2005). It was shown that diphenylmethyl selenocyanate was