Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
권호 표지

Effects of Vitamin E and Dehydroepiandrosterone on the Formation of Preneoplastic Lesions in Rat Hepatocellular Carcinogenesis

비타민 E와 Dehydroepiandrosterone이 화학적 발암원으로 유도한 쥐간의 전암성 병변에 미치는 영향

  • Kim, Sook-Hee (Division of Hotel Culinary Arts, Hyejeon College) ;
  • Choi, Hay-Mie (Department of Food and Nutrition, College of Human Ecology, Seoul National University)
  • 김숙희 (혜전대학 호텔조리계열) ;
  • 최혜미 (서울대학교 생활과학대학 식품영양학과)
  • Published : 2005.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

This study is designed to examine the effects of dietary supplementation with vitamin E and dehydroepiandrosterone (DHEA) on the formation of preneoplastic lesions in diethylnitrosamine (DEN) induced rat hepatocarcinogenesis. All Weaning male Sprague-Dawley rats were initiated by a single dose of DEN (200mg/kg body weight), subjected to two­thirds partial hepatectomy 3 weeks later and were sacrificed 8 weeks after DEN initiation. Two weeks after initiation, rats were fed Purina purified rodent diet 5053 (Ralston Purina Rat chow, USA) with $1.5\%$ (15,000 IU/kg diet) vitamin E, $0.5\%$ DHEA and both of those supplemented diet for 6 weeks. Placental glutathione S-transferase (GST-P) positive foci, the activities of catalase, total-glutathione peroxidase (GPx) , glutathione reductase (GR), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS) contents were decreased significantly by vitaimin E supplement. On the other hand GST-P positive foci number, Cu/Zn-superoxide dismutase (SOD) and glucose 6-phosphatase (G6Pase) activities weren't changed by vitamin E supplement. It might suggest that protective effect of vitamin E against hepatocarcinogens is not involved in the formation of the GST-P positive foci but related to the expansion of that. It seemed that vitamin E supplement helped endogenous defense system in carcinogenesis by decreasing TBARS contents, $H_2O_2$, organic peroxides. Therefore, vitamin E seemed to protect cell from free radical damage in carcinogenesis. By DHEA supplement liver weight and liver/body ratio were increased, the area and number of GST-P positive foci, the activities of catalase, GR, total GPx, GST and the TBARS contents were decreased significantly. On the other hand Cu/Zn-SOD and G6Pase activities weren't changed by DHEA supplement. In hepatocarcinogenesis the activities of antioxidant enzymes weren't increased by DHEA supplement. DHEA did not increase the oxidative stress, while DHEA seems to have anticarcinogenic effect in rats hepatocarcinogenesis.

Keywords

References

  1. Valko M, Kzakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem 266 (1-2): 37-56,2004 https://doi.org/10.1023/B:MCBI.0000049134.69131.89
  2. Ames BN. Dietary carcinogenesis and anticarcinogens. Science 221: 1256-1264,1995
  3. Watson RR, Leonard TK. Selenium and vitamin A, E and c: Nutrients with cancer prevention properties. J Am Diet Assoc 86: 505-510, 1986
  4. Harman D. Free radical theory of aging. In: the 'Free radical' disease Age 7: 111-131, 1984
  5. Krishnarnurthy S. The intriguing biological role of vitamin E. J Chem Ed 60: 456-467, 1983
  6. Watson RR, Leonard TK. Selenium and vitamin A, E and C: Nutrients with cancer prevention properties. J Am Diet Assoc 86: 505-510,1986
  7. Boscoboinik D, Szewczyk A, Hensey C, Azzi A. Inhibition of cell proliferation by $\alpha$ -tocopherol. Role of protein kinase C. J Biol Chem 266: 6188-6194, 1991
  8. Glauert HP, Lu Z, Kumar A, Bunaciu RP, Patel S, Tharappel JC, Stemm DN, Lehmler HJ, Lee EY, Robertson LW, Spear BT. Dietary vitamin E does not inhibit the promotion of liver carcinogenesis by polycWorinated biphenyls in rats. J Nutr 135 (2) : 283-286, 2005
  9. Shealy CN. A review of dehydroepiandrosterone (DHEA). Integr Physiol Behav Sci Sep-Dec 30(4): 308-313, 1995 https://doi.org/10.1007/BF02691603
  10. Schwartz AG, Pashko LL. Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase and longevity. Aging Res Rev 3 (2) : 171-187,2004 https://doi.org/10.1016/j.arr.2003.05.001
  11. Yen TY, Alan JA, Pearson DV, Acton IM. Prevention of obesity in Avy/a mice by dehydroepiandrosterone. Lipids 12: 409-413, 1977 https://doi.org/10.1007/BF02533624
  12. Coleman DL, Leiter EH, Schwizer RW. Therapeutic effects of dehydroepiandrosterone in diabetic mice. Diabetes 21: 830-833, 1982
  13. Gordon GB, Shantz LM, Talalay. Moderation of growth, differentiation and carcinogenesis by dehydroepiandrosterone. Adv Enzyme Reg 26: 355-382, 1987 https://doi.org/10.1016/0065-2571(87)90023-9
  14. Mayer D, Forstner K. hnpact of dehydroepiandrosterone on hepatocarcinogenesis if the rats.Int J Oncol 25 (4): 1021-1030, 2004
  15. Tunez I, Munoz MC, Montilla P. Treatment with Dehydroepiandrosterone prevents oxidative stress induced by 3-nitropropionic acid in synaptosomes. Pharmacology 74 (3): 106-111, 2005
  16. Cioline H, MacDonald C, Memon O, Dankwah M, Yeh GC. Dehydroepiandrosterone inhibits the expression of carcinogens-activation enzymes in vivo. Cancer 105 (3): 321-325,2003
  17. Hinson JP, Khan M. Dehydroepiandrosterone sulphate (DHEAS) inhibits growth of human vascular endothelial cells. Endocr Res 30(4): 667-671, 2004 https://doi.org/10.1081/ERC-200043956
  18. Swierczynski J, Mayer D. Dehydroepiandrosterone-induced lipid peroxidation in rat liver mitochondria. J Steroid Biochem Mol Biol Aug 58 (5-6): 599-603, 1996 https://doi.org/10.1016/0960-0760(96)00081-7
  19. Swierczynski J, Mayer D. Vitamin E prevents induction of carbonyl group formation in microsomal protein by dehydroepiandrosterone. Cancer 32 (2): 101-106, 1998 https://doi.org/10.1080/01635589809514726
  20. McIntosh MK, Goldfarb AH, Curtis LN, Cote PS. Vitamin E alters hepatic antioxidant enzymes in rats treated with dehydroepiandrosterone. J of Nutr 123: 216-224, 1993
  21. Ng HP, Wang YF, Lee CY, Hu ML. Toxicological and antioxidant effects of short-term dehydroepiandrosterone injection in young rats fed diets deficient or adequate in vitamin E. Food Chem Toxicol 37 (5): 503-508, 1999 https://doi.org/10.1016/S0278-6915(99)00032-0
  22. Rao MS, Subbarao V. Sex differences in dehydroepiandrosterone- induced hepatocarcinogenesis in the rat. Cancer Lett 13: 125 (1-1): 111-116, 1998 https://doi.org/10.1016/0304-3835(81)90136-1
  23. Ito N, Tsuda H, Tatematsu M, Inoue T, Tagawa Y, Aoki T, Uwagawa S, Kagawa M, Ogiso T, Masui T. Enhancing effect of various hepatocarcinogenesis on induction of prenesoplastic glutathione S-transferase placental form positive foci in rats-an approach for a new medium-term bioassay system. Carcinogenesis 9(3): 387-394,1988 https://doi.org/10.1093/carcin/9.3.387
  24. Krassavage WJ. Terhaar CJ. D-alpha tocopheryl poly (ethylene glycol) 1000 succinate acute toxicity, subchronic feeding, reproduction and teratologic studies in the rats. J Agric Food Chem 25: 273-278, 1977 https://doi.org/10.1021/jf60210a002
  25. Osigo T, Tatematsu M, Tarnano S, Tsuda H, Ito N. Comparative effects of carcinogenesis on the induction of placental glutathione S-transferase positive liver nodules in a short-term assay and of hepatocellular carcinogenesis in a long-term assay. Toxicol Pathol 13: 257-265, 1985 https://doi.org/10.1177/019262338501300402
  26. Misra HP, Fridovich I. Superoxide dismutase: a photochemical augmentation assay. Arch Biochem Biophys 181: 308, 1977
  27. Aebi H. Catalase in vitro. Methods in Enzymology 105: 121-126, 1984 https://doi.org/10.1016/S0076-6879(84)05016-3
  28. Carlberg I, Mannervick B. Glutathione reductase. Methods in Enzymology 113: 484-499, 1985 https://doi.org/10.1016/S0076-6879(85)13062-4
  29. Tappel AL. Glutathione peroxidase and hydroperoxides. Method Enzymology 52: 506-513, 1978 https://doi.org/10.1016/S0076-6879(78)52055-7
  30. Habig WH, Pabst MI, Jakoby WB. Glutathione S-transferase. J Biol Chem 249: 7130-7139,1974
  31. Baginski ES, Foa PP, Zak B. Glucose 6-phosphatase. Method of Enzymatic Analysis 2: 876-880, 1983
  32. Vaca CE, Harms-RingdaW M. Lipid peroxidation on the rat liver S9 fraction: Influence of membrane lipid composition. Mutation Res 162: 21-32, 1986
  33. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265-275, 1951
  34. Cleary MP. Effect of dehydroepiandrosterone treatment on liver metabolism in rats.Int J Biochem 22(3): 205-210, 1990 https://doi.org/10.1016/0020-711X(90)90331-V
  35. Cleary MP. The antiobesity effect of dehydroepiandrosterone in rats. Proc Soc Exp Biol Med Jan 196(1): 8-16, 1991
  36. Choi H, Kim J, Kim S. Suppressive effects of Vitamin E on the induction of placental Glutathione S-transferase (GST-P) positive foci and antioxidant enzyme activity in rat hepatocarcinogenesis. Korean J of Nutr 30 (7) : 803-8121, 1997
  37. Kim S, Kang S, Kim Y, Choi H. High Vitamin E Supplement is Needed to Have an Anticarcinogenic Effect of fish oil. Korean J Nutrition 31 (6): 1014-1023,1998
  38. Oberley LW, Buettner GR. Role of superoxide dismutase in cancer: A review. Cancer Res 39: 1141-1149,1979
  39. Togashi H, Shinzawa H, Wakobayoshi H, Nakamura T, Yamada N, Takahashi T, Ishikawa M. Activities of free oxygen radical scavenger enzymes in human liver. J Hepatol 11: 200-205, 1990 https://doi.org/10.1016/0168-8278(90)90114-7
  40. Kim KT, Park SC, Choi H. Induction of hepatomegaly and peroxisome activities by fish oil. Korean J of Lipidology 5 (2): 131-139,1995
  41. Aragno M, Tamagno E, Gatto V, Brignardello E, Parola S, Danni O, Boccuzzi G. Dehydroepiandrosterone protects tissues of Streptozotocin- treated rats against oxidative stress. Free Radic Biol Med Jun 26(11-12): 1467-1474,1999 https://doi.org/10.1016/S0891-5849(99)00012-X
  42. Bast A, Haenen Guido RMM. Cytochrome P-450 and vitamin E free radical reductase: formation of and protection against free radicals. In: Free radicals, Lipoproteins, and Membrane Lipids (Crastes de Paulet et al, eds), pp359-370. Plenum Press, NY, 1990
  43. Kitahara A, Yamazaki T, Ishikawa T, Camba EA, Kiyomi S. Changes in activities of glutathione peroxidase and glutathione reductase during chemical hepatocarcinogenesis in the rats. Jpn J Cancer Res 74: 649-655, 1983
  44. Salgado MC, Meton I, Egea M, Baanante IV. Transcriptional regulation of glucose-6-phosphatase catalytic subunit promoter by insulin and glucose in the carnivorous fish, Sparus aurata. J Molecular Endocrinology 33: 783-795, 2004 https://doi.org/10.1677/jme.1.01552
  45. Emmanuel F. Cellular biochemistry of the stepwise development of cancer with chemicals: G.H.A. Clows Memorial Lecture. Cancer Res 44: 5463-5474, 1984
  46. Williams JR. The effects of dehydroepiandrosterone on carcinogenesis, obesity, the immune system, and aging. Lipids 35 (3): 325-331,2000 https://doi.org/10.1007/s11745-000-0529-7