Attenuation of p-dimethylaminoazobenzene initiated genotoxicity and cytotoxicity in mice by the combined treatment of a traditional homeopathic remedy Chelidonium Majus 200C and vitamin-C

DOI QR코드

DOI QR Code

Biswas, Surjyo Jyoti;Karmakar, Susanta Roy;Khuda-Bukhsh, Anisur Rahman

  • 투고 : 2012.09.04
  • 심사 : 2012.11.20
  • 발행 : 2012.11.30

초록

The homeopathic remedy Chelidonium majus 200C (Chel-200) is traditionally used by homeopathic practitioners in liver ailments arising out of hepatotoxicity. The present investigation was aimed at examining whether vitamin C (L-ascorbic acid or AA), used in both traditional and orthodox medicines, can show better effects when used in combination with Chel-200, in favorably modifying the toxicological effects induced by the chronic feeding of p-dimethylaminoazobenzene (p-DAB, initiator) and phenobarbital (PB, promoter) in mice for 7 days through 120 days to induce hepatotoxicity and liver tumors. Mice were euthanized at 7, 15, 30, 60, 90, and 120 days of carcinogen feeding to assess various cytogenetical, biochemical and histological changes occurring in them. In a placebo controlled study, Chel-200 or the respective placebo (Alcohol-200C or Alc, "vehicle" of homeopathic drug), was orally administered to toxicant-fed mice. Sub-groups of the mice receiving Chel-200 were also fed either AA or an Alc placebo and their individual and conjoint effects were studied against the respective controls, to evaluate if the combination therapy of Chel-200 with AA can be of additional help in the amelioration of the toxicities generated by the toxicants. The combined feeding of Chel-200 and AA appeared to reduce the cytotoxic and genotoxic effects significantly, when compared to either only the Chel-200 or AA fed group. A similar trend was also obtained in the results of scanning and transmission electron microscopic studies of the livers. Experiments in other mammalian models are warranted to confirm if these drugs in combination could be used in palliative care of human patients with liver diseases including cancer.

키워드

p-dimethylaminoazobenzene;hepatocarcinogenesis;ultra-high dilution;L-ascorbic acid;homeopathy;Chelidonium Majus 200C

참고문헌

  1. Biswas SJ, Pathak S, Khuda-Bukhsh AR. Assessment of genotoxic and cytotoxic potentials of an anti-epileptic drug, phenobarbital, in mice: a time course study. Mutat Res. 2004;563:1-11. https://doi.org/10.1016/j.mrgentox.2004.05.016
  2. Alcain FJ, Buron MI. Ascorbate on cell growth and differentiation. J Bioenerg Biomembr. 1994;26:393-398. https://doi.org/10.1007/BF00762780
  3. Ames BN. Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science. 1983;221: 1256 -1264. https://doi.org/10.1126/science.6351251
  4. Bergmeyer HU, Brent E. Methods of enzymatic analysis. In: Bergmeyer HU ed. (New York, Academic Press), pp. 735-760, 1974
  5. Bhattacharyya SS, Paul S, Dutta S, Boujedaini N, Khuda-Bukhsh AR. Anti-oncogenic potentials of a plant coumarin (7-hydroxy-6 methoxy-coumarin) against 7-12-dimethylbenz anthracene-induced skin papilloma in mice: the possible role of several key signal proteins. Zhong Xi Yi Jie He Xue Bao. 2010;8:645-654. https://doi.org/10.3736/jcim20100708
  6. Biswas SJ, Bhattacharjee N, Khuda-Bukhsh AR. Efficacy of a plant extract (Chelidonium majus L) in combating induced hepatocarcinogenesis in mice. Food Chem Toxicol. 2008;46:1474-1487. https://doi.org/10.1016/j.fct.2007.12.009
  7. Biswas SJ, Khuda-Bukhsh AR. Effect of a homeopathic drug, Chelidonium, in amelioration of p-DAB induced hepatocarcinogenesis in mice. BMC Complementary Altern Med. 2002;2:4. https://doi.org/10.1186/1472-6882-2-4
  8. Biswas SJ, Khuda-Bukhsh AR. Ameliorating effect of an anti-oxidant (L-Ascorbic acid) on genotoxicity and cytotoxicity in mice during p-DAB-induced hepatocarcinogenesis. Ind J Cancer. 2004;41:79-87.
  9. Biswas SJ, Khuda-Bukhsh AR. Cytotoxic and genotoxic effects of the azo-dye p-dimethylaminoazobenzene in mice: a time-course study. Mutat Res. 2005;587:1-8. https://doi.org/10.1016/j.mrgentox.2005.06.011
  10. Block G. Vitamin C and Cancer prevention: The epidemiological evidence. Am J Clin Nutr. 1991;53:270S-280S. https://doi.org/10.1093/ajcn/53.1.270S
  11. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52: 302-310. https://doi.org/10.1016/S0076-6879(78)52032-6
  12. Cahlikova L, Opletal L, Kurfürst M, Macakova K, Kulhánkova A, Hostalkova A. Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Chelidonium majus (Papaveraceae). Nat Prod Commun. 2010;5:1751-1754.
  13. Colombo ML, Bosisio E. Pharmacological activities of Chelidonium majus L. (Papaveraceae). Pharmacol Res. 1996;33:127-134. https://doi.org/10.1006/phrs.1996.0019
  14. Dawson EB, Harris WA, Powell LC. Relationship between ascorbic acid and male fertility. World Rev Nutr Diet. 1990;62:1-26.
  15. Frei BL, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A. 1989;86:6377- 6381. https://doi.org/10.1073/pnas.86.16.6377
  16. Halliwell B. Vitamin C and genomic stability. Mutat Res. 2001;475:29-35. https://doi.org/10.1016/S0027-5107(01)00072-0
  17. Jackson JA, Riordan HD, Hunninghake RE, Riordan N. High dose intravenous vitamin C and long time survival of a patient with cancer of the head of the pancreas. J Orthomol Med.1995;10:87-88.
  18. Kaegi E. Unconventional therapies for cancer: Vitamins A, C and E. The task force on alternative therapies of the Canadian breast cancer research initiative. CMAJ. 1998;158:1483-1488.
  19. Kaya B. Anti-genotoxic effect of ascorbic acid on mutagenic dose of three alkylating agents. Turk J Biol. 2003;27:241-246.
  20. Khuda-Bukhsh AR, Pathak S. Homeopathic drug discovery: theory update and methodological aspect. Expert Opin Drug Discov. 2008;3:979-990. https://doi.org/10.1517/17460441.3.8.979
  21. Khuda-Bukhsh AR. Towards understanding molecular mechanisms of action of homeopathic drugs: an overview. Mol Cell Biochem. 2003;253:339-345. https://doi.org/10.1023/A:1026048907739
  22. Khuda-bukhsh AR. Laboratory research in homeopathy: Integr Cancer Ther.2006;5:1-13. https://doi.org/10.1158/1535-7163.MCT-05-0310
  23. Lee KW, Lee HJ, Kang KS, Lee CY. Preventive effects of vitamin C on carcinogenesis. Lancet. 2002;359:172.
  24. Levine M. New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med. 1986;314:892-902. https://doi.org/10.1056/NEJM198604033141407
  25. Li XL, Yao JY, Zhou ZM, Shen JY, Ru HS, Liu XL. Activity of the chelerythrine, a quaternary benzo[c]phenanthridine alkaloid from Chelidonium majus L. on Dactylogyrus intermedius. Parasitol Res. 2011;109:247-252. https://doi.org/10.1007/s00436-011-2320-9
  26. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin-Phenol reagent. J Biol Chem. 1951;193:265-275.
  27. Meadows GG, Pierson HF, Abdallah RM. Ascorbate in the treatment of experimental transplanted melanoma. Am J Clin Nutr. 1991;54:1284-1291. https://doi.org/10.1093/ajcn/54.6.1284s
  28. Moore J, Phipps K, Marcer D, Lewith G. Why do people seek treatment by alternative medicine? Br Med J (Clin Res Ed). 1985;290:28-29 https://doi.org/10.1136/bmj.290.6461.28
  29. Murata M, Kobayashi M, Kawanishi S. Mechanism of oxidativeDNAdamage induced by a heterocyclic amine 2-amino-3,8-dimethylimidaze[4,5f] quinoxaline. Jpn J Cancer Res. 1999;90:268-275. https://doi.org/10.1111/j.1349-7006.1999.tb00743.x
  30. Ohnishi S, Murata M, Degawa M, Kawanishi S. Oxidative DNA damage induced by an N-hydroxy metabolite of carcinogenic 4-dimethylaminoazobenzene. Jpn J Cancer Res. 2001;92:23-29. https://doi.org/10.1111/j.1349-7006.2001.tb01043.x
  31. Park JE, Cuong TD, Hung TM, Lee I, Na M, Kim JC, Ryoo S, Lee JH, Choi JS, Woo MH, Min BS, Alkaloids from Chelidonium majus and their inhibitory effects on LPS-induced NO production in RAW264.7 cells. Bioorg Med Chem. 2011;21:6960-6963. https://doi.org/10.1016/j.bmcl.2011.09.128
  32. Prasad KN. Modulation of the effects of tumor therapeutic agents by vitamin C. Life Sci. 1980;27:275-280. https://doi.org/10.1016/0024-3205(80)90194-0
  33. Sauberlich HE. Pharmacology of vitamin C. Annu Rev Nutr. 1994;14:371-391 https://doi.org/10.1146/annurev.nu.14.070194.002103
  34. Schmid W. The micronucleus test for cytogenetic analysis, Chemical Mutagens, Principles and Methods for their Detection. (New York and London: Plenum Press), pp. 31-53, 1976
  35. Teschke R, Glass X, Schulze J. Herbal hepatotoxicity by Greater Celandine (Chelidonium majus): causality assessment of 22 spontaneous reports. Regul Toxicol Pharmacol. 2011;61:282-291. https://doi.org/10.1016/j.yrtph.2011.08.008
  36. Teschke R, Frenzel C, Glass X, Schulze J, Eickhoff A. Greater Celandine hepatotoxicity: a Clinical review. Ann Hepatol. 2012;11:838-848.
  37. Walter K, Schutt C. Acid and alkaline phosphatases in serum (Two point method), In: Bergmeyer HU. ed. (New York, Academic Press), pp. 856-860, 1974.
  38. Wattenberg LW. Inhibition of carcinogenesis by minor dietary constituents. Cancer Res. 1992;52:2085s-2091s.
  39. Wattenberg LW. Inhibition of Carcinogenesis by Minor Dietary Constituents. cancer Res.52. 2085s-2091s. 1992)
  40. Wenzel U, Nickel A, Kuntz S, Daniel H. Ascorbic acid suppresses drug induced apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions. Carcinogenesis. 2004;25:703-712.
  41. Wyrobek AJ, Gordon LA, Burkhart JG, Francis MW, Kapp RW Jr, Letz G, Malling HV, Topham JC, Whorton MD. An evaluation of the mouse sperm morphology test and other sperm in nonhuman mammals. A report of the U.S. environmental protection agency gene-tox program. Mutat Res. 1983;115:1-72. https://doi.org/10.1016/0165-1110(83)90014-3