Browse > Article

The Protective Effects of Garlic against Carbon tetrachloride-induced Hepatotoxicity  

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)
Publication Information
Journal of Preventive Medicine and Public Health / v.35, no.3, 2002 , pp. 221-228 More about this Journal
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
Garlic; Carbon tetrachloride; Trichloroethylene; Liver/injuries; Protective agents;
Citations & Related Records
연도 인용수 순위
  • Reference
1 NCI(National Cancer Institute). Carcinogenesis bioassay oftrichloroethylene. Washington DC:USDREW publication; 1976
2 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   DOI   ScienceOn
3 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   DOI   ScienceOn
4 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   DOI   PUBMED
5 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   DOI   ScienceOn
6 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   DOI
7 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   DOI   ScienceOn
8 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   DOI   ScienceOn
9 Kamanna VS, Chandrasekhara N. Hypocholesteremic activity of different fractions of garlic. Indian J Med Res 1984; 79(4): 580-583
10 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   DOI   ScienceOn
11 Cojocel C, Beuter W, Muller W, Mayer D. Lipid peroxidation: a possible mechanism of trichloroethylene-induced nephrotoxicity. Toxicology 1989;55(1-2): 131-141   DOI   ScienceOn
12 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   DOI   ScienceOn
13 Teel RW. Effect of capsaicin on rat liver S9-mediated metabolism and DNA binding of aflatoxin. Nutr Cancer 1991; 15(1): 27-32   DOI   PUBMED   ScienceOn
14 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   PUBMED
15 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   DOI   ScienceOn
16 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   DOI   ScienceOn
17 van Duuren BL, Banerjee S. Covalent interactionof metabolites of the carcinogen trichloroethylene in rat hepatic microso-meso Cancer Res 1976;36(7): 2419-2422   PUBMED
18 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   DOI   ScienceOn
19 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   DOI   ScienceOn
20 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with folin phenol reagent. J Biol Chem 1951; 193: 401-404
21 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   DOI
22 Louria DB, Bogden JD. The dangers from limited exposure to carbon tetrachloride. Crit Rev Toxieol 1980; 7(2): 177-188   DOI
23 Flanagan RJ, Ruprah M, Meredith TJ, Ramsey JD. An introduction to the clinical toxicology of volatile substances. Drug Saf 1990; 5(5): 359-383   DOI   ScienceOn
24 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   DOI
25 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   DOI   ScienceOn
26 McGregor D, Lang M. Carbon tetrachl-oride: genetic effects and other modes of action. Mutat Res 1996; 366(3): 181-195   DOI
27 Lambert N, Freedman RB. The latency of rat liver microsomal protein disulphide-somerase. BiochemJ 1985; 228(3): 635-645   DOI
28 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
29 Guengerich FP. Catalytic selectivity of human cytochrome P450 enzymes: relevance to drug metabolismand toxicity. Toxicol Lett 1994;70(2): 133-138   DOI   ScienceOn
30 Ernst E. Cardioprotection and garlic. Lancet 1997; 349(9045): 131   DOI   PUBMED
31 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   DOI
32 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   DOI   ScienceOn
33 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   DOI   ScienceOn
34 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   PUBMED
35 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   DOI   ScienceOn
36 Defalque RJ. Pharmacology and toxicology of trichloroethylene: A critical review of the world literature. Clin Pharmacal Ther 1961; 2(5): 665-802   DOI
37 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   DOI   ScienceOn
38 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   DOI   ScienceOn
39 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   DOI   ScienceOn
40 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   DOI   ScienceOn
41 Ariga T, Oshiba S, Tamada T. Platelet aggregation inhibitor in garlic. Lancet 1981; 1(8212): 150-151   PUBMED
42 Dausch JG, Nixon DW. Garlic: a review of its relationship to malignant disease. Prev Med 1990; 19(3): 346-361   DOI   ScienceOn
43 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   DOI   ScienceOn
44 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   DOI   ScienceOn
45 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   DOI   ScienceOn
46 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   DOI   ScienceOn
47 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   DOI
48 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   DOI   ScienceOn
49 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   DOI   ScienceOn
50 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   DOI   ScienceOn
51 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
52 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   PUBMED
53 Waters EM, Gerstner HB, Huff JE. Trichloroethylene. I. An overview. J Toxicol EnvironHealth 1977;2(3):671-707   DOI   ScienceOn
54 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   DOI   ScienceOn
55 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   DOI
56 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   DOI   ScienceOn
57 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   DOI
58 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
59 Adetumbi MA, Lau BH. Allium sativum (garlic)--a natural antibiotic. Med Hypotheses 1983; 12(3): 227-237   DOI   ScienceOn
60 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   PUBMED
61 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   DOI
62 Omura T, Sato R. The carbon monoxide-binding pigment of liver microsomes. J BioI Chem 1964; 239(7): 2370-2378
63 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95(2): 351-358   DOI   ScienceOn
64 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   DOI   ScienceOn
65 Belman S. Onion and garlic oils inhibit tumor promotion. Carcinogenesis 1983; 4(8): 1063-1065   DOI   ScienceOn
66 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   PUBMED