lesion scoring and p450 isoenzyme activity in liver of hepatocarcinogenesis rats treated with strobilanthes crispus

abstract objective : in this study, we have undertaken efforts to ascertain the anticancer potency of s. crispus (sc) extract on diethylnitrosamine (den) and acetylaminofluorene (aaf) induced hcc with special attention to hepatic drug metabolism and to investigate the effect of sc on preneoplastic marker enzyme activity specifically of microsomal aniline hydroxylase (ah) activity and lesion scoring in rats treated with den and aaf and controls. materials and methods : thirty male sprague dawley rats were divided to six equal number groups. in the first three groups, hepatocellular carcinoma was induced with diethylnitrosamine and acetylaminofluorene.  three groups in each branch were randomly assigned to receive  5% w/v of sc extract, glycyrrhizin or no treatment. after 12 weeks of treatment, the rats were sacrificed. lesion scoring analysis and aniline hydroxylase assays were performed as outcome measures. results : the obtained results have shown a significant, increase (p<0.05) of liver microsome ah in cancer group rats after 12 weeks. treatment with glycyrrhizin caused decrease in liver ah activity compared to control group. meanwhile, treatment with sc caused overall decrease in liver ah activity almost near to control group. meanwhile, microscopic observation of the lesion score during hepatocarcinogenesis revealed that cells of cancer group without treatment were severely necrotic at week 12. s. crispus treatment reduced the severity in cancer group rats at week 12.  conclusion :   s. crispus only ameliorated the cancer incidence in the liver, however did not fully recover the liver tumor similar to the normal cells. this might be due to short experimental duration. the chemopreventive action may be due to the scavenging of the reactive oxygen radicals from the system, as well as inhibition of the enzymes responsible for the activation of den. in this study, sc extract may act as a chemopreventive agent which exerts its protective effects by inhibition of enzymes involved in metabolic activation of carcinogen (phase i enzyme i.e anh) keywords : strobilanthes crispus, hepatocarcinogenesis, lesion score and aniline hydroxylase please cite this article as: hanachi p , fauziah o , asmah r. lesion scoring and p450 isoenzyme activity in liver of hepatocarcinogenesis rats treated with strobilanthes crispus. iran j cancer prev. 2008; 1(1): 12-16. references 1. premalatha b, sachdanandam p. potency of semocarpus anacarddium. linn nut milk extract against aflatoxin b1-induced hepatocarcinogenesis reflection on microsomal biotransformation enzymes. pharmacological research. 2000; 42(2): 161-166. 2. lewis  w.h., elvin-lewis, m.p.f. from plants affecting man’s health : medical botany. in cancer. edited by wiley, a. new york: interscience publication. 1997; 105-148. 3. rates, s.m.k. plants as source of drugs. toxicon 2001; 39: 603-613. 4. sunatro p.a. materia medika indonesia. jakarta: penerbit ditektoral pengawasan  obat dan  makanan ; 1977. 5. hanachi p, shamaan na ramli j, arshad jh,. syed ma.. the effect of benzo(a)pyrene on glutathione s-transferase, glutathione peroxidase in the liver and kidney mouse mus musculus. pakistan journal medical science. 2003; 19: 197-202. 6. tepsuwan a.,  kupradinum p., kusamran w.r. : effect of  siamese cassia leaves on the activities of chemical carcinogen metabolizing enzymes and on mammary gland carcinogenesis in the rat. mutation research: 1999; 428 : 363-373. 7. conney a.h, wang z.y, huang m.t, ho c.t,yang c.s. (1992): inhibitory effect of oral administration of green tea on tumourigenesis by ultraviolet light, 12-0-tetradecanoylphorbol-13-acetate and n-nitrosodiethylamine in mice. in cancer chemoprevention. edited by w. lee, l. martin, b.w. charles and k. gary. new york : crc press inc. ; 1992 : 362 8. elizabeth manickam. the nutritional and antinutritional composition of strobilanthes crispus (l) bremek and its anticancer effect during hepatocarcinogenesis. master thesis, university putra malaysia. 1999. 9. solt d, farber e. new principle for the analysis of chemical carcinogenesis. nature 1976; 263: 701-703. 10. hesham m. s,  mostafa h. m,  o'connor p.j, rafferty j.a. , michael j. d.  evidence for the presence of active cytochrome p450 systems in schistosoma mansoni and schistosoma haematobium adult worms. febs letters 2002; 519(1-3): 205-209. 11. stevens a., lowe j.s, young b. from staging and grading of chronic hepatitis: in wheater’s basic histopathology: toronto; 2002: 157. 12. imai y, ito a, sato r. evidence for biochemically different types of vesicles in the hepatic microsomal fraction. j biochem. (tokyo) 1966, 60: pp 417. 13. waxman d.j, morrissey j.j, leblanc g.a. female-predominant rat hepatic p450 forms j (iiei) and 3 (iiai) are under hormonal regulatory               controls distinct form those of the sex-specific p450 forms. endocrinol. 1984; 124: 2954-2966. 14. bradford m.m.a: rapid and sensitive method for quantitation of microgram quantities of protein utilising the principle of protein dye binding. anal. biochem 1976; 50: 249-253. 15. jeena k.j, joyk.c, kuttan r. effect of emblica officinalis, phyllanthus amarus and picrorrhiza kurroa on n-nitrosodiethylamine induced hepatocarcinogenesis. cancer letters 1999; 136: 11-16.