Journal of Preventive Medicine and Public Health

The Korean Society for Preventive Medicine (대한예방의학회)
권호 표지

The Protective Effects of Garlic against Carbon tetrachloride-induced Hepatotoxicity

마늘에 의한 사염화탄소 간독성의 보호 효과

  • Lee, Jong-Moon (Department of Preventive Medicine and Community Health, College of medicine, Chung-Ang University) ;
  • Park, Jung-Duck (Department of Preventive Medicine and Community Health, College of medicine, Chung-Ang University) ;
  • Hong, Yeon-Pyo (Department of Preventive Medicine and Community Health, College of medicine, Chung-Ang University) ;
  • Choi, Byung-Sun (Department of Preventive Medicine and Community Health, College of medicine, Chung-Ang University)
  • 이종문 (중앙대학교 의과대학 예방의학교실) ;
  • 박정덕 (중앙대학교 의과대학 예방의학교실) ;
  • 홍연표 (중앙대학교 의과대학 예방의학교실) ;
  • 최병선 (중앙대학교 의과대학 예방의학교실)
  • Published : 2002.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : The purpose of this study was to find the protective effects of garlic on the halogenated hydrocarbon induced hepatotoxicities, and the possible protection mechanisms involved. Methods : Male Sprague-Dawley rats received garlic (0.5%) or regular diet, for 4 weeks. This was followed by a single dose of corn oil (the controls), carbon tetrachloride (400mg/kg body weight) and trichloroethylene (2,000mg/kg body weight) being administered to each diet group. Blood samples were collected 24 hours fellowing the administration, and the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALD activities measured. The liver samples were studied for their cytochrome P450 and CYP2E1 contents, lipid peroxidation and histopathology. Results : rho results for the group receiving the 9.5% garlic diet showed a slight decrease of CYP2E1 expression compared with the regular diet group. Carbon tetrachloride was significantly decreased the CYP2E1 contents in both the regular and garlic diet groups, but the trichloroethylene remained unchanged. Garlic did not decrease the lipid peroxidation of the liver in the control group, but attenuated the increase of lipid peroxidation caused by carbon tetrachloride. Garlic attenuated the increase of both the serum AST and ALT activities caused by carbon tetrachloride. The histopathelogical observations also showed that garlic attenuated centrilobular necrosis and vacuolar degenerative changes significantly in the carbon tetrachloride treated group. Conclusions : The results indicate that garlic attenuates the carbon tetrachloride-induced hepatotoxicity, through the prevention of the metabolic activation and lipid peroxidation.

Keywords

References

  1. Louria DB, Bogden JD. The dangers from limited exposure to carbon tetrachloride. Crit Rev Toxieol 1980; 7(2): 177-188 https://doi.org/10.3109/10408448009037488
  2. Flanagan RJ, Ruprah M, Meredith TJ, Ramsey JD. An introduction to the clinical toxicology of volatile substances. Drug Saf 1990; 5(5): 359-383 https://doi.org/10.2165/00002018-199005050-00005
  3. Reuber MD, Glover EL. Cirrhosis and carcinoma of the liver in male rats given subcutaneous carbon tetrachloride. J Natl Cancer Inst 1970; 44(2): 419-27
  4. Defalque RJ. Pharmacology and toxicology of trichloroethylene: A critical review of the world literature. Clin Pharmacal Ther 1961; 2(5): 665-802 https://doi.org/10.1002/cpt196125665
  5. Waters EM, Gerstner HB, Huff JE. Trichloroethylene. I. An overview. J Toxicol EnvironHealth 1977;2(3):671-707 https://doi.org/10.1080/15287397709529469
  6. Davidson IW, Beliles RP. Consideration of the target organ toxicity of trichloroethylene in terms of metabolite toxicity and pharmacokinetics. Drug Metab Rev 1991; 23(5-6): 493-599 https://doi.org/10.3109/03602539109029772
  7. NCI(National Cancer Institute). Carcinogenesis bioassay oftrichloroethylene. Washington DC:USDREW publication; 1976
  8. van Duuren BL, Banerjee S. Covalent interactionof metabolites of the carcinogen trichloroethylene in rat hepatic microso-meso Cancer Res 1976;36(7): 2419-2422
  9. Bull RI, Templin M, Larson JL, Stevens DK. The role of dichloroacetate in the hepatocarcinogenicity of trichloroethy-lene. Toxicol Lett 1993; 68(1-2): 203-211 https://doi.org/10.1016/0378-4274(93)90131-G
  10. Guengerich FP. Catalytic selectivity of human cytochrome P450 enzymes: relevance to drug metabolismand toxicity. Toxicol Lett 1994;70(2): 133-138 https://doi.org/10.1016/0378-4274(94)90156-2
  11. McGregor D, Lang M. Carbon tetrachl-oride: genetic effects and other modes of action. Mutat Res 1996; 366(3): 181-195 https://doi.org/10.1016/S0165-1110(96)90027-5
  12. Suarez KA, Carlson GP, Fuller GC. Effect of phenobarbital or 3-methylcho-lanthrene pretreatment on carbon tetrachloride-induced lipid peroxidation in rat liver. Toxicol Appl Pharmacol 1975; 34(2): 314-319 https://doi.org/10.1016/0041-008X(75)90037-X
  13. Lindstrom TD, Anders MW, Remmer H. Effect of phenobarbital and diethyl maleate on carbon tetrachloride toxicity in isolated rat hepatocytes. Exp Mol Pathol 1978; 28(1): 48-57 https://doi.org/10.1016/0014-4800(78)90063-1
  14. Johansson I, Ingelman-Sundberg M. Carbon tetrachloride-induced lipid peroxidation dependent on an ethanol-inducible form of rabbit liver microsomal cytochrome P-450. FEBS Lett 1985; 183(2): 265-269 https://doi.org/10.1016/0014-5793(85)80790-0
  15. Barton HA, Bull R, Schultz I, Andersen ME. Dichloroacetate (DCA) dosimetry: interpreting DCA-induced liver cancerdose response and the potential for DCA to contribute to trichloroethylene-induced liver cancer. ToxicolLett 1999; 106(1): 9-21 https://doi.org/10.1016/S0378-4274(99)00016-8
  16. Bull RJ, Sanchez 1M, Nelson MA, Larson JL, Lansing AJ. Liver tumorinduction in B6C3Fl mice by dichloroacetate and trichloroacetate. Toxicology 1990; 63(3): 341-359 https://doi.org/10.1016/0300-483X(90)90195-M
  17. DeAngelo AB, Daniel FB, Stober JA, Olson GR. The carcinogenicity of dichloroacetic acid in the male B6C3Fl mouse. Fundam Appl Toxicol 1991; 16(2): 337-347 https://doi.org/10.1016/0272-0590(91)90118-N
  18. Volkel W, Friedewald M, Lederer E, Pahler A, Parker J, Dekant W. Biotrans-formation of perchloroethene: dose-dependent excretion of trichloroacetic acid, dichloroacetic acid, and N-acetyl-S(trichlorovinyl)-L-cysteine in rats and humans after inhalation. Toxicol Appl Pharmacol 1998; 153(1): 20-27 https://doi.org/10.1006/taap.1998.8548
  19. Qureshi AA, Din ZZ, Abuirmeileh N, Burger WC, Ahmad Y, Elson CEo Suppression of avian hepatic lipid metabolism by solvent extracts of garlic: impact on serum lipids. J Nutr 1983; 113(9): 1746-1755
  20. Kamanna VS, Chandrasekhara N. Hypocholesteremic activity of different fractions of garlic. Indian J Med Res 1984; 79(4): 580-583
  21. Ariga T, Oshiba S, Tamada T. Platelet aggregation inhibitor in garlic. Lancet 1981; 1(8212): 150-151
  22. Apitz-Castro R, Cabrera S, Cruz MR, Ledezma E, Jain MK. Effects of garlic extract and of three pure components isolated from it on human platelet aggregation, arachidonate metabolism, release reaction and platelet ultrastructure. Thromb Res 1983; 32(2): 155-169 https://doi.org/10.1016/0049-3848(83)90027-0
  23. Adetumbi MA, Lau BH. Allium sativum (garlic)--a natural antibiotic. Med Hypotheses 1983; 12(3): 227-237 https://doi.org/10.1016/0306-9877(83)90040-3
  24. Dausch JG, Nixon DW. Garlic: a review of its relationship to malignant disease. Prev Med 1990; 19(3): 346-361 https://doi.org/10.1016/0091-7435(90)90034-H
  25. Dorant E, van den Brandt PA, Goldbohm RA, Hermus RI, Sturmans F. Garlic and its significance for the prevention of cancer in humans: a critical view. Br J Cancer 1993; 67(3): 424-429 https://doi.org/10.1038/bjc.1993.82
  26. Ernst E. Cardioprotection and garlic. Lancet 1997; 349(9045): 131 https://doi.org/10.1016/S0140-6736(05)60911-7
  27. Buiatti E, Palli D, Bianchi S, Decarli A, Amadori D, Avellini C, Cipriani F, Cocco P, Giacosa A, Lorenzini L. A case-control study of gastric cancer and diet in Italy. Int J Cancer 1989; 44(4): 611-616 https://doi.org/10.1002/ijc.2910440409
  28. You WC, Blot WJ, Chang YS, Ershow A, Yang ZT, An Q, Henderson BE, Fraumeni JF Jr, Wang TG. Allium vegetables and reduced risk of stomach cancer. J Natl Cancer Inst 1989; 81(2): 162-164 https://doi.org/10.1093/jnci/81.2.162
  29. Matsuda T, Takada N, Yano Y, Wanibu-chi H, Otani S, Fukushima S. Dose-dependent inhibition of glutathione S-transferase placental form-positive hepatocellular foci induction in the rat by methyl propyl disulfide and propylene sulfide from garlic and onions. Cancer Lett 1994; 86(2): 229-234 https://doi.org/10.1016/0304-3835(94)90083-3
  30. Samaranayake MD, Wickramasinghe SM, Angunawela P, Jayasekera S, Iwai S, Fukushima S. Inhibition of chemically induced liver carcinogenesis in Wistar rats by garlic (Allium sativum). Phytother Res 2000; 14(7): 564-567 https://doi.org/10.1002/1099-1573(200011)14:7<564::AID-PTR664>3.0.CO;2-Z
  31. Belman S. Onion and garlic oils inhibit tumor promotion. Carcinogenesis 1983; 4(8): 1063-1065 https://doi.org/10.1093/carcin/4.8.1063
  32. Sadhana AS, Rao AR, Kucheria K, Bijani V. Inhibitory action of garlic oil on the initiation of benzo[a]pyrene-induced skin carcinogenesis in mice. Cancer Lett 1988; 40(2): 193-197 https://doi.org/10.1016/0304-3835(88)90010-9
  33. Hussain SP, Jannu LN, Rao AR. Chemopreventive action of garlic on methylc holanthrene - induced carcinogenesis in the uterine cervix of mice. Cancer Lett 1990; 49(2): 175-180 https://doi.org/10.1016/0304-3835(90)90155-Q
  34. Sparnins VL, Barany G, Wattenberg LW. Effects of organosulfur compounds from garlic and onions on benzo[a]pyrene-induced neoplasia and glutathione Stransferase activity in the mouse. Carcinogenesis 1988; 9(1): 131-134 https://doi.org/10.1093/carcin/9.1.131
  35. Hu JJ, Yoo JS, Lin M, Wang EJ, Yang CS. Protective effects of dially1 sulfide on acetaminophen-induced toxicities. Food Chem Toxicol 1996; 34(10): 963-969 https://doi.org/10.1016/S0278-6915(96)00057-9
  36. Lin MC, Wang EJ, Patten C,Lee MJ, Xiao F, Reuhl KR, Yang CS. Protectiveeffectof diallyl sulfone against acetaminophen-induced hepatotoxicity in mice. J Biochem Toxicol 1996; 11(1): 11-20 https://doi.org/10.1002/(SICI)1522-7146(1996)11:1<11::AID-JBT2>3.0.CO;2-Y
  37. Wang BH, Zuze1 KA, Rahman K, Billington D. Protective effects of aged garlic extract against bromobenzene toxicity to precision cut rat liver slices. Toxicology 1998; 126(3): 213-222 https://doi.org/10.1016/S0300-483X(98)00018-3
  38. Wang BH, Zuzel KA, Rahman K, Billington D. Treatment with aged garlic extract protects against bromo benzene toxicity to precision cut rat liver slices. Toxicology 1999; 132(2-3): 215-225 https://doi.org/10.1016/S0300-483X(99)00004-9
  39. Wang EJ, Li Y, Lin M, Chen L, Stein AP, Reuh1 KR, Yang CS. Protective effects of garlic and related organosulfur compounds on acetaminophen-induced hepatotoxicity in mice. Toxicol Appl Pharmacol 1996; 136(1): 146-154 https://doi.org/10.1006/taap.1996.0018
  40. Horie T, Murayama T, Mishima T, Itoh F, Minamide Y, Fuwa T, Awazu S. Protection of liver microsomal membra-nes from lipid peroxidation by garlic extract. Planta Med 1989; 55(6): 506-508 https://doi.org/10.1055/s-2006-962081
  41. Imai J, Ide N, Nagae S, Moriguchi T, Matsuura H, Itakura Y. Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Med 1994; 60(5): 417-420 https://doi.org/10.1055/s-2006-959522
  42. Kagawa K, Matsutaka H, Yamaguchi Y, Fukuhama C. Garlic extract inhibits the enhanced peroxidation and production of lipids in carbon tetrachloride-induced liver injury. Jpn J Pharmacol 1986; 42(1): 19-26 https://doi.org/10.1254/jjp.42.19
  43. Kourounakis PN, Rekka EA. Effect on active oxygen species of alliin and Allium sativum (garlic) powder. Res Commun Chem Pathol Pharmacol 1991; 74(2): 249-252
  44. Pessayre D, Cobert B, Descatoire V, Degott C, Babany G, Funck-Brentano C, Delaforge M, Larrey D. Hepatotoxicity of trichloroethylene-carbon tetrachloride mixtures in rats. A possible consequence of the potentiation by trichloroethylene of carbon tetrachloride-induced lipid peroxidation and liver lesions. Gastroenterology 1982; 83(4): 761-772
  45. Cojocel C, Beuter W, Muller W, Mayer D. Lipid peroxidation: a possible mechanism of trichloroethylene-induced nephrotoxicity. Toxicology 1989;55(1-2): 131-141 https://doi.org/10.1016/0300-483X(89)90180-7
  46. Lambert N, Freedman RB. The latency of rat liver microsomal protein disulphide-somerase. BiochemJ 1985; 228(3): 635-645 https://doi.org/10.1042/bj2280635
  47. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with folin phenol reagent. J Biol Chem 1951; 193: 401-404
  48. Omura T, Sato R. The carbon monoxide-binding pigment of liver microsomes. J BioI Chem 1964; 239(7): 2370-2378
  49. Laemmli UK, Beguin F, Gujer-Kellen-berger G. A factor preventing the major head protein of bacteriophage T4 from random aggregation. J Mol BioI 1970; 47(1): 69-85 https://doi.org/10.1016/0022-2836(70)90402-X
  50. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95(2): 351-358 https://doi.org/10.1016/0003-2697(79)90738-3
  51. Boyd JN, Babish JG, Stoewsand GS. Modification by beet and cabbage diet of aflatoxin AFB1-induced rat plasma $\alpha$-foetoprotein elevation, hepatic tumori-genesis, and mutagenicity of urine. Food Chem Toxicol 1982; 20(1): 47-52 https://doi.org/10.1016/S0278-6915(82)80008-2
  52. Teel RW. Effect of capsaicin on rat liver S9-mediated metabolism and DNA binding of aflatoxin. Nutr Cancer 1991; 15(1): 27-32 https://doi.org/10.1080/01635589109514108
  53. Xu Y, Ho CT, Amin SG, Han C, Chung FL. Inhibition of tobacco specific nitrosamine-induced lung tumorigenesis in A/J mice by green tea and its major polyphenol as antioxidants. Cancer Res 1992; 52(14): 3875-3879
  54. Park K, Choi H. Modification of hepatic microsomal cytochrome P450 2E1 enzyme by garlic powder in rat hepatocarcinogenesis. J Biochem Mol BioI 1997; 30(1): 73-79
  55. Williams GM, Tanaka T, Maeura Y. Dose-related inhibition of aflatoxin AFB I induced hepatocarcinogenesis by the phenolic antioxidants, butylated hydroxyanisole and butylated hydroxytoluene. Carcinogenesis 1986; 7(7): 1043-1050 https://doi.org/10.1093/carcin/7.7.1043
  56. Mandel HG, Manson MM, Judah DJ, Simpson JL, Green JA, Forrester LM, Wolf CR, Neal GE. Metabolic basis for the protective effect of the antioxidant ethoxyquin on aflatoxin AFB1 hepato-carcinogenesis in the rat. Cancer Res 1987; 47(19): 5218-5223
  57. Masuda Y, Nakayama N. Protectiveeffect of diethyldithiocarbamate and carbon disulfide against liver injury induced by various hepatotoxic agents. Biochem Pharmacol 1982; 31(17):2713-2725 https://doi.org/10.1016/0006-2952(82)90124-1
  58. Ip C, Lisk DJ. Modulation of phase I and phase II xenobiotic-metabolizing enzymes by selenium-enriched garlic in rats. Nutr Cancer 1997; 28(2): 184-188 https://doi.org/10.1080/01635589709514573
  59. Siess MH, Le Bon AM, Canivenc-Lavier MC, Suschetet M. Modification of hepatic drug-metabolizing enzymes in rats treated with alkyl sulfides. Cancer Lett 1997; 120(2): 195-201 https://doi.org/10.1016/S0304-3835(97)00309-1
  60. Guyonnet D. BelloirC, SuschetetM, Siess MH. Antimutagenicactivity of organosul-fur compounds from Allium is associated with phase II enzyme induction. Mutat Res 2001; 495(1-2): 135-145 https://doi.org/10.1016/S1383-5718(01)00205-4
  61. Lee KM, Muralidhara S, White CA, Bruckner JV. Mechanisms of the dose-dependent kinetics of trichloroethylene: oral bolus dosing of rats. Toxicol Appl Pharmacol 2000; 164(1): 55-64 https://doi.org/10.1006/taap.2000.8892
  62. Song BJ, Veech RL, Park SS, Gelboin HV, Gonzalez FJ. Induction of rat hepatic N-nitrosodimethylarnine demethylase by acetone is due to protein stabilization. J BioI Chem 1989; 264(6): 3568-3572
  63. Wang PY, Kaneko T, Tsukada H, Nakano M, Nakajima T, Sato A. Time courses of hepatic injuries induced by chloroform and by carbon tetrachloride: comparison of biochemical and histopathological changes. Arch Toxicol 1997; 71(10): 638-645 https://doi.org/10.1007/s002040050438
  64. Manno M, Ferrara R, Cazzaro S, Rigotti P, Ancona E. Suicidal inactivation of human cytochrome P-450 by carbon tetrachloride and halothane in vitro. PharmacoI ToxicoI 1992;70(1): 13-18 https://doi.org/10.1111/j.1600-0773.1992.tb00418.x
  65. Sheweita SA, Abd EI-Gabar M, Bastawy M. Carbon tetrachloride-induced changes in the activity of phase II drug-metaboli-zing enzyme in the liver of malerats: role of antioxidants. Toxicology 2001; 165(23): 217-224 https://doi.org/10.1016/S0300-483X(01)00429-2
  66. Wong FW, Chan WY, Lee SS. Resistance to carbon tetrachloride-induced epatoto-xicity in mice which lack CYP2E1 expression. Toxicol Appl Pharmacol 1998; 153(1): 109-118 https://doi.org/10.1006/taap.1998.8547