Protective Effect of Hydroalcoholic Extract of Clove on Thioacetamide-Induced Hepatotoxicity Animal Model
Abstract
Background: The drug-induced liver injury (DILI) has a wide range of clinical presentations, from asymptomatic liver enzyme elevations to cirrhosis. Herbal dietary supplements may be beneficial to reduce the risk of hepatotoxicity. This study aimed to evaluate the effects of different doses of clove extracts on humoral factors in rats with hepatotoxicity induced by thioacetamide. Materials and Methods: In this experimental study, rats were divided into nine groups (10 rats per each). The Control group received no treatment. The Sham group was treated with oral administration of distilled water (0.5 ml) for 21 days. The positive control group received thioacetamide (50 mg/kg for three days) intraperitoneally. The clove group was divided into three subgroups and given daily oral administrations of 50, 150, and 300 mg/kg of clove hydroalcoholic extracts (for 21 days). Rats in the experimental group were divided into three subgroups and subjected to 50 mg/kg thioacetamide injection after receiving hydroalcoholic extracts of clove (50, 150, and 300 mg/kg, respectively) for 21 days in the last three days. All rats were sacrificed after 48 hours to measure liver function parameters (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total plasma protein, and albumin). Results: The rats that received thioacetamide showed liver damage by increased serum liver biomarkers and decreased levels of total plasma protein and albumin compared to the control group. The different doses of clove extract resulted in a significant improvement of liver damage by reduced serum liver enzymes levels and increased total plasma protein and albumin. Conclusion: Oral administration of the different doses of the clove extract (50, 150, and 300 mg/kg) for 21 consecutive days could significantly improve the changes associated with serum biomarkers of hepatotoxicityReferences
Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transpl. 2004;10(8):1018-23.
https://doi.org/10.1002/lt.20204
PMid:15390328
Potpara TS, Lip GY. Drug-induced liver injury with oral anticoagulants: a threat or not? Heart. 2017;103(11):809-11.
https://doi.org/10.1136/heartjnl-2016-310983
PMid:28213369
Abdel Salam OM, Mohammed NA, Sleem AA, Farrag AR. The effect of antidepressant drugs on thioacetamide-induced oxidative stress. Eur Rev Med Pharmacol Sci. 2013;17(6):735-44.
Singh GN, Kumar N. A Review on Drug Induced Hepatotoxicity and Its Management By Herbal Drugs. World J Pharmacy and Pharmaceut Sci. 2017;6(8):446-71.
https://doi.org/10.20959/wjpps20178-9760
Ferrajolo C, Scavone C, Donati M, Bortolami O, Stoppa G, Motola D, et al. Antidepressant-Induced Acute Liver Injury: A Case-Control Study in an Italian Inpatient Population. Drug Saf. 2018;41(1):95-102.
https://doi.org/10.1007/s40264-017-0583-5
PMid:28770534
Watkins PB. Tacrine and transaminases. Alzheimer Disease & Associated Disorders. 1994;8:S39.
https://doi.org/10.1097/00002093-199424000-00005
Hartleb M, Biernat L, Kochel A. Drug-induced liver damage--a three-year study of patients from one gastroenterological department. Med Sci Monit. 2002;8(4):CR292-6.
Bleibel W, Kim S, D'Silva K, Lemmer ER. Drug-induced liver injury: review article. Dig Dis Sci. 2007;52(10):2463-71.
https://doi.org/10.1007/s10620-006-9472-y
PMid:17805971
Abboud G, Kaplowitz N. Drug-induced liver injury. Drug Saf. 2007;30(4):277-94.
https://doi.org/10.2165/00002018-200730040-00001
PMid:17408305
Yuan L, Kaplowitz N. Mechanisms of drug-induced liver injury. Clin Liver Dis. 2013;17(4):507-18.
https://doi.org/10.1016/j.cld.2013.07.002
PMid:24099014 PMCid:PMC3793205
Liu Y, Wu F. Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment. Environ Health Perspect. 2010;118(6):818-24.
https://doi.org/10.1289/ehp.0901388
PMid:20172840 PMCid:PMC2898859
Holt MP, Ju C. Mechanisms of drug-induced liver injury. AAPS J. 2006;8(1):E48-54.
https://doi.org/10.1208/aapsj080106
PMid:16584133 PMCid:PMC2751423
Mays ET, Christopherson W. Hepatic tumors induced by sex steroids. Semin Liver Dis. 1984;4(2):147-57.
https://doi.org/10.1055/s-2008-1040654
PMid:6087460
Shapiro H, Ashkenazi M, Weizman N, Shahmurov M, Aeed H, Bruck R. Curcumin ameliorates acute thioacetamide-induced hepatotoxicity. J Gastroenterol Hepatol. 2006;21(2):358-66.
https://doi.org/10.1111/j.1440-1746.2005.03984.x
PMid:16509859
Salem AM, Mahdy KA, Hassan NS, El-Saeed GS, Farrag AR, Monem MA. Nigella sativa seed reduced galectin-3 level and liver fibrosis in thioacetamide-induced liver injury in rats. J Arab Soc Med Res. 2017;12(2):46.
https://doi.org/10.4103/jasmr.jasmr_8_17
Farrag AR, Omara EA, Galal AF, El-Toumy SA, Hassan NS, Sharaf HA, et al. Antifibrotic effects of Punica granatum peels through stimulation of hepatic stellate cell apoptosis in thioacetamide-induced liver fibrosis in rats. J Arab Soc Med Res. 2017;12(2):56.
https://doi.org/10.4103/jasmr.jasmr_12_17
Iqubal A, Iqubal MK, Haque SE. Experimental hepatotoxicity inducing agents: a Review. Int J Clin Pharmacol Res. 2016;6(11):325-5.
Amin ZA, Bilgen M, Alshawsh MA, Ali HM, Hadi AH, Abdulla MA. Protective Role of Phyllanthus niruri Extract against Thioacetamide-Induced Liver Cirrhosis in Rat Model. Evid Based Complement Alternat Med. 2012;2012:241583.
https://doi.org/10.1155/2012/241583
PMid:22649471 PMCid:PMC3357973
Chen TM, Subeq YM, Lee RP, Chiou TW, Hsu BG. Single dose intravenous thioacetamide administration as a model of acute liver damage in rats. Int J Exp Pathol. 2008;89(4):223-31.
https://doi.org/10.1111/j.1365-2613.2008.00576.x
PMid:18422601 PMCid:PMC2525782
Sahin S, Eulenburg V, Heinlein A, Villmann C, Pischetsrieder M. Identification of eugenol as the major determinant of GABAA-receptor activation by aqueous Syzygium aromaticum L.(clove buds) extract. J Funct Foods. 2017;37:641-9.
https://doi.org/10.1016/j.jff.2017.08.033
Beltrán-Villalobos KL, Déciga-Campos M, Aguilar-Mariscal H, González-Trujano ME, Martínez-Salazar MF, De los Ángeles Ramírez-Cisneros M, et al. Synergistic antinociceptive interaction of Syzygium aromaticum or Rosmarinus officinalis coadministered with ketorolac in rats. Biomed Pharmacother. 2017;94:858-64.
https://doi.org/10.1016/j.biopha.2017.07.166
PMid:28802239
Zou P, Hu S, Li W, Liu D, Chen Y. Quantitative Assessment of Germicidal Efficacy of Syzygium aromaticum Dried Flower Bud. Asian J Tradit Med. 2017;12(2):39-44.
Venugopal K, Rather HA, Rajagopal K, Shanthi MP, Sheriff K, Illiyas M, et al. Synthesis of silver nanoparticles (Ag NPs) for anticancer activities (MCF 7 breast and A549 lung cell lines) of the crude extract of Syzygium aromaticum. J Photochem Photobiol B. 2017;167:282-9.
https://doi.org/10.1016/j.jphotobiol.2016.12.013
PMid:28110253
Zhang H, Peng X, Li X, Wu J, Guo X. The application of clove extract protects Chinese-style sausages against oxidation and quality deterioration. Korean J Food Sci Anim Resour. 2017;37(1):114.
https://doi.org/10.5851/kosfa.2017.37.1.114
PMid:28316478 PMCid:PMC5355575
Radha krishnan K BS, Azhagu Saravana Babu P, Sasikala M, Sabina K, Archana G, Sivarajan M, et al. Antimicrobial and antioxidant effects of spice extracts on the shelf life extension of raw chicken meat. Int J Food Microbiol. 2014;171:32-40.
https://doi.org/10.1016/j.ijfoodmicro.2013.11.011
PMid:24308943
Babuskin S, Babu PA, Sasikala M, Sabina K, Archana G, Sivarajan M, et al. Antimicrobial and antioxidant effects of spice extracts on the shelf life extension of raw chicken meat. Int J food Microbiol. 2014;171:32-40.
https://doi.org/10.1016/j.ijfoodmicro.2013.11.011
PMid:24308943
Sharma A, Rajendran S, Srivastava A, Sharma S, Kundu B. Antifungal activities of selected essential oils against Fusarium oxysporum f. sp. lycopersici 1322, with emphasis on Syzygium aromaticum essential oil. J biosci bioengi. 2017;123(3):308-13.
https://doi.org/10.1016/j.jbiosc.2016.09.011
PMid:27876218
Abdel‐Wahhab MA, Aly SE. Antioxidant property of Nigella sativa (black cumin) and Syzygium aromaticum (clove) in rats during aflatoxicosis. J Appl Toxicol. 2005;25(3):218-23.
https://doi.org/10.1002/jat.1057
PMid:15856529
Naji KM, Al-Shaibani ES, Alhadi FA, Al-Soudi SA, D'souza MR. Hepatoprotective and antioxidant effects of single clove garlic against CCl4-induced hepatic damage in rabbits. BMC Complement Altern Med. 2017;17(1):1-2.
https://doi.org/10.1186/s12906-017-1916-8
PMid:28818066 PMCid:PMC5561638
Tanko Y, Mohammed A, Okasha MA, Umah A, Magaji R. Anti-nociceptive and anti-inflammatory activities of ethanol extract of Syzygium aromaticum flower bud in wistar rats and mice. Afr J Tradit Complement Altern Med. 2008;5(2):209-12.
https://doi.org/10.4314/ajtcam.v5i2.31275
PMid:20161939 PMCid:PMC2816534
Dwivedi V, Shrivastava R, Hussain S, Ganguly C, Bharadwaj M. Comparative anticancer potential of clove (Syzygium aromaticum)-an Indian spice-against cancer cell lines of various anatomical origin. Asian Pac J Cancer Prev. 2011;12(8):1989-93.
Osada J, Aylagas H, Sanchez-Vegazo I, Gea T, Millan I, Palacios-Alaiz E. Effect of S-adenosyl-L-methionine on thioacetamide-induced liver damage in rats. Toxicol Lett. 1986;32(1-2):97-106.
https://doi.org/10.1016/0378-4274(86)90054-8
Adam SI, Mohamed SB, Abdelgadir WS. Effects of the Aqueous Extract of Clove (" Syzygium aromaticum") on Wistar Rats. Br J Pharmacol Toxicol. 2013;4(6):262-6.
https://doi.org/10.19026/bjpt.4.5410
Schumann G, Aoki R, Ferrero CA, Ehlers G, Férard G, et al. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37° C: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC): Scientific Division, Committee on Reference Systems for Enzymes (C-RSE): Part 8. Reference procedure for the measurement of catalytic concentration of α-amylase:[α-Amylase: 1, 4-α-D-glucan 4-glucanohydrolase (AMY), EC 3.2. 1.1]. Clinical Chemistry and Laboratory Medicine (CCLM). 2006;44(9):1146-55.
https://doi.org/10.1515/CCLM.2006.212
PMid:16958612
WMA Statement on Animal Use in Biomedical Research. 2020. Available from: https://www.wma.net/policies-post/wma-statement-on-animal-use-in-biomedical-research/.
Saleh DO, Abdel Jaleel GA, El-Awdan SA, Oraby F, Badawi M. Thioacetamide-induced liver injury: protective role of genistein. Can J Physiol Pharmacol. 2014;92(11):965-73.
https://doi.org/10.1139/cjpp-2014-0192
PMid:25358106
Starkel P, Leclercq IA. Animal models for the study of hepatic fibrosis. Best Pract Res Clin gastroenterol. 2011;25(2):319-33.
https://doi.org/10.1016/j.bpg.2011.02.004
PMid:21497748
Madani H, Talebolhosseini M, Asgary S, Naderi GH. Hepatoprotective activity of Silybum marianum and Cichorium intybus against thioacetamide in rat. Pak J Nutr. 2008;7(1):172-6.
https://doi.org/10.3923/pjn.2008.172.176
Hajovsky H, Hu G, Koen Y, Sarma D, Cui W, Moore DS, Staudinger JL, Hanzlik RP. Metabolism and toxicity of thioacetamide and thioacetamide S-oxide in rat hepatocytes. Chem Res Toxicol. 2012;25(9):1955-63.
https://doi.org/10.1021/tx3002719
PMid:22867114 PMCid:PMC3444651
Saad RA, EL-Bab MF, Shalaby AA. Attenuation of acute and chronic liver injury by melatonin in rats. J Taibah Univ Sci. 2013;7(2):88-96.
https://doi.org/10.1016/j.jtusci.2013.04.008
Abdel-Rahman MK, Abd El-Megeid AA. Hepatoprotective effect of soapworts (Saponaria officinalis), pomegranate peel (Punica granatum L) and cloves (Syzygium aromaticum linn) on mice with CCl4 hepatic intoxication. World J Chem. 2006;1(1):41-6.
Sun F, Hayami S, Ogiri Y, Haruna S, Tanaka K, Yamada Y, et al. Evaluation of oxidative stress based on lipid hydroperoxide, vitamin C and vitamin E during apoptosis and necrosis caused by thioacetamide in rat liver. Biochim Biophys Acta Mol Basis. Dis 2000;1500(2):181-5.
https://doi.org/10.1016/S0925-4439(99)00100-3
Prasad R, Ali S, Khan LA. Hepatoprotective effect of Syzygium aromaticum extract on acute liver injury induced by thioacetamide. Int J Pharm Clin Res. 2010;2:68-71.
Yogalakshmi B, Viswanathan P, Anuradha CV. Investigation of antioxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats. Toxicology. 2010;268(3):204-12.
https://doi.org/10.1016/j.tox.2009.12.018
PMid:20036707
Ali S, Prasad R, Mahmood A, Routray I, Shinkafi TS, Sahin K, et al. Eugenol-rich fraction of Syzygium aromaticum (clove) reverses biochemical and histopathological changes in liver cirrhosis and inhibits hepatic cell proliferation. J Cancer Prev. 2014;19(4):288.
https://doi.org/10.15430/JCP.2014.19.4.288
PMid:25574464 PMCid:PMC4285960
Al-Mufarrej SI, Al-Baadani HH, Fazea EH. Effect of level of inclusion of clove (Syzygium aromaticum) powder in the diet on growth and histological changes in the intestines and livers of broiler chickens. S Afr J of Anim Sci. 2019;49(1):166-75.
https://doi.org/10.4314/sajas.v49i1.19
Abdel-Wahhab MA, Omara EA, Abdel-Galil MM, Hassan NS, Nada SA, Saeed A, et al. Zizyphus spina-christi extract protects against aflatoxin B1-intitiated hepatic carcinogenicity. Afr J Tradit Complement Altern Med. 2007;4(3):248.
https://doi.org/10.4314/ajtcam.v4i3.31216
Abdel‐Wahhab MA, Aly SE. Antioxidant property of Nigella sativa (black cumin) and Syzygium aromaticum (clove) in rats during aflatoxicosis. J Appl Toxicol. 2005;25(3):218-23.
https://doi.org/10.1002/jat.1057
PMid:15856529
Afrasiabie M, Mokhtari M. Effect of Dianthus carryophyllu extract on the induced hepatotoxicity by Gentamicin in rats. J Gorgan Univ Med Sci. 2017;18(4):22-9.
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