Anticarcinogenic activity of allylmercaptocaptopril against aflatoxin-B1 induced liver carcinoma in rats
Amaç: Bu çalışma güçlü bir karaciğer kanser nedeni olan aflatoksin B1 tarafından oluşturulan karaciğer kanserine karşı aliyilmerkaptokaptopril’inin (AMC) koruyucu etkisinin hücresel ve moleküler mekanizmasını araştırmak amacıyla yapıldı. Metod: Bu çalışmada, biz heksokinaz, fosfoizomeraz ve aldolaz gibi glikolitik enzimlerin ve glukoz-6-fosfataz ve fruktoz 1,6 bifosfataz gibi glukoneogenik enzimlerin saptanması ile enzimatik karaciğer fonksiyonlar ile birlikte karaciğerde AMC’nin koruyucu etkisini saptamaktır. Total protein, DNA ve RNA içeriğinin saptanması etkisini açığa çıkarmak için yapıldı. Bulgular: Ratlarda aflatoksin B1 tedavisi control grubuyla karşılaştırıldığında belirgin olarak heksokinaz, fosfoglukoizomeraz ve aldolaz gibi glikolitik enzimlerin düzeylerinde artma ve serum total protein, glukoneogenik enzimler, DNA ve RNA içeriğinde belirgin azalma ile ile sonuçlanmaktadır. AMC’nin uygulanması enzimatik karaciğer fonksiyonları ve total protein, DNA ve RNA içeriğinde yenileme ile sonuçlandı. Sonuç: AMC hepatoselüler kanserde glikolitik ve glukoneogenik enzimler, DNA ve RNA sentez fonksiyonlarını modüle etme yeteneğine sahip olduğu gösterilmiştir.
Ratlarda aflatoksin-B1'in oluşturduğu karaciğer kanserinde aliyilmerkaptokaptopril'in antikanserojen etkisi
Aim: The present study was aimed to investigate the cellular and molecular mechanisms of protective effects of allylmercaptocaptopril (AMC) against liver carcinoma induced by Aflatoxin B1, a potent inducer of liver cancer. Method: In this study we determined the protective effect of AMC on liver tissue, as well as on enzymatic liver functions by estimating glycolytic enzymes like hexokinase, phosphoisomerase and aldolase, gluconeogenic enzymes like glucose-6-phosphatase and fructose 1,6 biphosphatase. Determination of total protein, DNA and RNA content also made to elucidate its action. Result: Aflatoxin B1 treatment to rats resulted in significantly elevated levels of glycolytic enzymes like hexokinase, phosphoglucoisomerase and aldolase and along with significant decrease in serum total protein, gluconeogenic enzymes and DNA and RNA content when compared to the control rats. The administration of AMC to the hepatocellular carcinoma bearing rats resulted in restoration of most of enzymatic liver functions and also total protein content, DNA and RNA content. Conclusion: Allylmercaptocaptopril has an ability to modulate the function of glycolytic and gluconeogenic enzymes, DNA and RNA synthesis in hepatocellular carcinoma which proved its anticarcinogenic activity.
___
- 1. Path FRC, Ali Abdel S. An update on the pathogenesis and pathology of Hepatocellular Carcinoma. Bah Med Bull 2007;29:1-8.
- 2. Asmaa IG, Shahid AK, Mireille BT, Imam W, Simon D, Robinson T. Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis. World J of Gastroenterol 2008;14:4300-8.
- 3. Noore A, Monica R, Deborah B. Epidemiology of primary liver cancer. Cancer Forum 2009;33:1-5.
- 4. Daniel MK, Daniel ZV, Misael U, Nahum MS. Hepatocellular carcinoma: An overview. Annal Hep 2006;5:16-24.
- 5. William FW, Agostino M. Captopril as a chemopreventive agent. Free Patent Online 1993; Pt no.5192524.
- 6. Amitai E, Mirelman D, Peleg E, Wilchek M, Miron T, Rabinkov A, MorOron H, Rosenthal T. The Effects of Allicin on Weight in Fructose-Induced Hyperinsulinemic, Hyperlipidemic, Hypertensive Rats. American J Hyper 2003;16:1053-6.
- 7. Miron T, Rabinkov A, Peleg E, et al. Allylmercaptocaptopril: a new antihypertensive drug. Am J Hypertens 2004; 17: 71-3.
- 8. Stoll A, Seebeck E. Die synthesis des naturlichen Aliins und senier drei optish aktiven Isomerasen. Hel Chem Acta 1948;31:189-210.
- 9. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin-Phenol reagents. J Biol Chem 1951;193:265-75.
- 10. Darrow RA, Colowick SP. Methods Enzymol 1962; 226-7.
- 11. Horrocks JE, Ward J, King JA. A routine method for the determination of phosphoglucoisomerase activity in body fluid. J Clin Pathol 1963;16: 248-52.
- 12. Bergmeyer HU. Methods of Enzymatic Analysis, Second Edition, 1974, Volume I, 430
- 13. Taussky HH, Shorr EJ. Biol Chem 1953; 202:675-85.
- 14. Nordlie, RC, Arion WJ. Methods Enzymology 1966;9:619- 25.
- 15. Gancedo JM, Gancedo C. Fructose 1,6-disphosphatase, phospho fructokinase and glucose-6-phosphate dehydrogenase from fermenting and non-fermenting yeasts. Arch Microbiol 1971;76:132-8.
- 16. Kamali M, Manhouri H. A Modified Orcinol Reaction for RNA Determination. Clin Chem 1969;15:390-2.
- 17. Burton K. A Study of the Conditions and Mechanism of the Diphenylamine Reaction for the Colorimetric Estimation of Deoxyribonucleic Acid. Biochem J 1956;62:315-23.
- 18. Bannasch P, Mayer D, Hacker HJ. Hepatocellular glycogenesis and hepatocarcinogenesis. Biochim Biophys Acta 1980;605:217-45.
- 19. Hertzfeld A, Greengard O. Enzyme activities in human fetal and neoplastic tissues. Cancer 1980;46:2047-54.
- 20. Parry DM, Pedersen PL. Intracellular localization and properties of particulate hexokinase in the Novikoff ascites tumour. J Biol Chem 1983;258:10904-12.
- 21. Arora KK, Pedersen PL. Functional significance of mitochondrial bound hexokinase in tumour cell metabolism. J Biol Chem 1988;263:17422-28.
- 22. Campbell DM, King, EJ. Serum phosphatases and glycolytic enzymes in cancer of the breast. Biochem J 1962; 82:23-8.
- 23. Hennipman A, Van Oirschot BA, Smits J, Rijksen G,Stacil GEJ. Heterogeneity of glycolytic enzyme activity and isozyme composition of pyruvate kinase in breast cancer. Tumour Biol 1988;9:178-88.
- 24. Quistorff, B. Gluconeogenesis in periportal and perivenous hepatocytes of rat liver, isolated by a new high-yield digitonin/ collagenase perfusion technique. Biochem J 1985;229:221-6.
- 25. Graham MM, Spence AM, Muzi M, Abbot GL. Deoxyglucose kinetics in rat brain tumour. J CerebBlood Flow Metab 1989;9:315-22.
- 26. Weber G, Cantero A. Comparison of carbohydrate metabolism in normal and neoplastic liver. EnzymeStudies. Acta Unio Internat Contra Cancrum 1960;16:1002.
- 27. Ellis EN, Burnette JJ, Sedlack R, Dyas C, Blackemore WSA. Surgery 1991;173:329.
- 28. Lancaster MC. Comparative Aspects of Aflatoxin-induced Hepatic Tumors. Cancer Research 1968; 28:2288-92.
- 29. Roebuck BD, Maxuitenko YY. In: Eaton DL, Groopman JD, editors. Toxicology of aflatoxins. San Diego: Academic Press, 1994:27-43.