Gentamicin Induced Hepatotoxicity: An approach of Hepatoprotecion by Garlic

R. Mishra¹ , V.K. Shrivastava²

Section:Research Paper, Product Type: Isroset-Journal
Vol.5 , Issue.6 , pp.150-156, Dec-2018

CrossRef-DOI:   https://doi.org/10.26438/ijsrbs/v5i6.150156

Online published on Jan 01, 2018

Copyright © R. Mishra , V.K. Shrivastava . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
 

View this paper at   Google Scholar | DPI Digital Library

XML View     PDF Download

How to Cite this Paper

1414 Views    359 Downloads    234 Downloads

Abstract :
Gentamicin hepatotoxicity is a major clinical drawback. This investigation was performed to scrutinize the effect of garlic extract as a herbal antidote on liver toxicity after treatment with gentamicin in male albino rats. Gentamicin is a widely used anti-infective broad-spectrum antibiotic of aminoglycoside family. Side effects of gentamicin medication occur due to free radical formation. Garlic, the bulb of Allium sativum, is universally used as a spice and also known for its medicinal and antioxidant properties. Forty adult male albino rats, Rattus norvegicus were randomly classified into four groups of ten each. Group 1 received 0.9% normal saline orally per day and served as control while group 2 received gentamicin intramuscularly per day, however group 3 received both gentamicin intramuscularly per day and garlic extract orally per day, while group 4 received only garlic extract orally per day for 30 and 60 days respectively. Gentamicin caused various structural and functional changes in hepatic cell, increased glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), acid phosphatase (ACP), alkaline phosphatase (ALP) and decreased total protein and creatinine level. Co-administration of garlic extract to rats ameliorates the gentamicin toxicity at some extent in hepatic cells as shown in the results of biochemical, enzymological and histopathological studies. Garlic extract was effective in recovering the level of hepatic enzymes, biochemical markers and histological alterations; hence, it may be concluded that garlic reduces the gentamicin hepatotoxicity in rats.

Key-Words / Index Term :
Gentamicin; Hepatotoxicity; Garlic extract; Hepatoprotection; Male Rattus norvegicus

References :
[1] Russmann S, Kullak-Ublick GA, Grattagliano I. Current concepts of mechanisms in drug-induced hepatotoxicity. Current medicinal chemistry. 2009 Aug 1;16(23):3041-53.
[2] Mukazayire MJ, Allaeys V, Calderon PB, Stévigny C, Bigendako MJ, Duez P. Evaluation of the hepatotoxic and hepatoprotective effect of Rwandese herbal drugs on in vivo (guinea pigs barbiturate-induced sleeping time) and in vitro (rat precision-cut liver slices, PCLS) models. Experimental and toxicologic pathology. 2010 May 1;62(3):289-99.
[3] Kaplowitz N. Drug-induced liver injury. Clinical Infectious Diseases. 2004 Mar 1;38(Supplement_2):S44-8.
[4] Holt MP, Ju C. Mechanisms of drug-induced liver injury. The AAPS journal. 2006 Mar 1;8(1):E48-54.
[5] Lee WM. Drug-induced hepatotoxicity. New England Journal of Medicine. 2003 Jul 31;349(5):474-85.
[6] Hermann T. Aminoglycoside antibiotics: old drugs and new therapeutic approaches. Cellular and molecular life sciences. 2007 Jul 1;64(14):1841-52.
[7] Krause KM, Serio AW, Kane TR, Connolly LE. Aminoglycosides: an overview. Cold Spring Harbor perspectives in medicine. 2016 Jun 1;6(6):a027029.
[8] Davies J, Davis BD. Misreading of Ribonucleic Acid Code Words Induced by Aminoglycoside Antibiotics THE EFFECT OF DRUG CONCENTRATION. Journal of Biological Chemistry. 1968 Jun 25;243(12):3312-6.
[9] Davis BD, Chen LL, Tai PC. Misread protein creates membrane channels: an essential step in the bactericidal action of aminoglycosides. Proceedings of the National Academy of Sciences. 1986 Aug 1;83(16):6164-8.
[10] Begg EJ, Barclay ML, Duffull SB. A suggested approach to once‐daily aminoglycoside dosing.British journal of clinical pharmacology. 1995 Jun 1;39(6):605-9.
[11] Kahlmeter G, Dahlager JI. Aminoglycoside toxicity–a review of clinical studies published between 1975 and 1982. Journal of Antimicrobial chemotherapy. 1984 Jan 1;13(suppl_A):9-22.
[12] EDSON RS, TERRELL CL. The aminoglycosides. InMayo Clinic Proceedings 1991 Nov 1 Vol. 66, No. 11, pp. 1158-1164. Elsevier.
[13] Edson RS, Terrell CL. The aminoglycosides. InMayo Clinic Proceedings 1999 May 1 Vol. 74, No. 5, pp. 519-528. Elsevier.
[14] Priuska EM, Schacht J. Formation of free radicals by gentamicin and iron and evidence for an iron/gentamicin complex. Biochemical pharmacology. 1995 Nov 27;50(11):1749-52.
[15] Huang MY, Schacht J. Formation of a cytotoxic metabolite from gentamicin by liver.1990.
[16] Crann SA, Huang MY, McLaren JD, Schacht J. Formation of a toxic metabolite from gentamicin by a hepatic cytosolic fraction.
[17] Alarifi SA, Alkahtani S, Al-Doaiss AA. Detection of apoptotsis induced by gentamicin in rat hepatocytes. International Journal of Zoological Research. 2009 Jan 1;5(4):161-70.
[18] Alkhatani S, Alarifi SA and Al-Doaiss A. Apoptotsis pathways induced by gentamicin in rat hepatocytes. In Orlando International Academic Conference. 2012 vol:1, pp. 265-272.
[19] Seif HS. Physiological changes due to hepatotoxicity and the protective role of some medicinal plants.Beni-suef university journal of basic and applied sciences. 2016 Jun 1;5(2):134-46.
[20] Suleria HA, Butt MS, Khalid N, Sultan S, Raza A, Aleem M, Abbas M. Garlic (Allium sativum): diet based therapy of 21st century–a review. Asian Pacific Journal of Tropical Disease. 2015 Apr 1;5(4):271-8.
[21] Khatua TN, Adela R, Banerjee SK. Garlic and cardioprotection: insights into the molecular mechanisms. Canadian journal of physiology and pharmacology. 2013 Mar 6;91(6):448-58.
[22] Khanum F, Anilakumar KR, Viswanathan KR. Anticarcinogenic properties of garlic: a review. Critical reviews in food science and nutrition. 2004 Nov 1;44(6):479-88.
[23] Ankri S, Mirelman D. Antimicrobial properties of allicin from garlic. Microbes and infection. 1999 Feb 1;1(2):125-9.
[24] Chung LY. The antioxidant properties of garlic compounds: allylcysteine, alliin, allicin, and allyl disulfide. Journal of medicinal food. 2006 Jun 1;9(2):205-13.
[25] Schafer G, H Kaschula C. The immunomodulation and anti-inflammatory effects of garlic organosulfur compounds in cancer chemoprevention. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2014 Feb 1;14(2):233-40.
[26] Bayan L, Koulivand PH, Gorji A. Garlic: a review of potential therapeutic effects. Avicenna journal of phytomedicine. 2014 Jan;4(1):1.
[27] Omar SH, Al-Wabel NA. Organosulfur compounds and possible mechanism of garlic in cancer.Saudi Pharmaceutical Journal. 2010 Jan 1;18(1):51-8.
[28] Vazquez-Prieto MA, Rodriguez Lanzi C, Lembo C, Galmarini CR, Miatello RM. Garlic and onion attenuates vascular inflammation and oxidative stress in fructose-fed rats. Journal of nutrition and metabolism. 2011 Aug 25;2011.
[29] Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent.Journal of biological chemistry. 1951 Nov 1;193(1):265-75.
[30] Toro G and Ackermann P. Quantitative determination of creatinine orheparinzed plasma urine by colorimetric kinetic method.Practical clinical chemistry 1st ed., Little Brown and Company, Boston.1975 pp237–238.
[31] Reitman S, Frankel S. A colorimetric method for the determination of serum glutamicoxalacetic and glutamic pyruvic transaminases. American journal of clinical pathology. 1957 Jul 1;28(1):56-63.
[32] Bergmeyer HU and Bernt E. 1963, In: Methods of enzymatic analysis, edited by HU Bergmeyer, Academic Press, Weimheim, NY and London, 837.
[33] Ehrlich P. 1886, Fragekasten Zeitschnft Fur Wissenschaflliche Mikroskopic und Fur Mikroskopische Technik, 3, 150.
[34] Tukey JW. Comparing individual means in the analysis of variance. Biometrics. 1949 June 1:99-114.
[35] Ali BH. Gentamicin nephrotoxicity in humans and animals: some recent research. General Pharmacology: The Vascular System. 1995 Nov 1;26(7):1477-87.
[36] Rosselet JP, Marquez J, Meseck E, Murawski A, Hamdan A, Joyner C, Schmidt R, Migliore D, Herzog HL. ISOLATION, PURIFICATION, AND CHARACTERIZATION OF GENTAMICIN. Antimicrobial agents and chemotherapy. 1963;161:14.
[37] Weinstein MJ, Luedemann GM, Oden EM, Wagman GH, Rosselet JP, Marquez JA, Coniglio CT, Charney W, Herzog HL, Black J. Gentamicin, 1 a new antibiotic complex from Micromonospora. Journal of medicinal chemistry. 1963 Jul;6(4):463-4.
[38] Bekheet SH, Awadalla EA, Salman MM, Hassan MK. Prevention of hepatic and renal toxicity with bradykinin potentiating factor (BPF) isolated from Egyptian scorpion venom (Buthusoccitanus) in gentamicin treated rats. Tissue and Cell. 2013 Apr 1;45(2):89-94.
[39] Arjinajarn P, Chueakula N, Pongchaidecha A, Jaikumkao K, Chatsudthipong V, Mahatheeranont S, Norkaew O, Chattipakorn N, Lungkaphin A. Anthocyanin-rich Riceberry bran extract attenuates gentamicin-induced hepatotoxicity by reducing oxidative stress, inflammation and apoptosis in rats. Biomedicine & Pharmacotherapy. 2017 Aug 1;92:412-20.
[40] Banerjee SK, Maulik M, Manchanda SC, Dinda AK, Das TK, Maulik SK. Garlic-induced alteration in rat liver and kidney morphology and associated changes in endogenous antioxidant status.Food and Chemical Toxicology. 2001 Aug 1;39(8):793-7.
[41] Slack A, Yeoman A, Wendon J. Renal dysfunction in chronic liver disease. Critical care. 2010 Apr;14(2):214.
[42] Hayden K, van Heyningen C. Measurement of total protein is a useful inclusion in liver function test profiles. Clinical chemistry. 2001 Apr 1;47(4):793-4.
[43] Thapa BR, Walia A. Liver function tests and their interpretation. The Indian Journal of Pediatrics. 2007 Jul 1;74(7):663-71.
[44] Tai PC, Davis BD.Triphasic concentration effects of gentamicin on activity and misreading in protein synthesis. Biochemistry. 1979 Jan;18(1):193-8.
[45] Schwarze PE, Seglen PO. Effects of antibiotics on protein synthesis and degradation in primary cultures of rat hepatocytes.In vitro. 1981 Jan 1;17(1):71-6.
[46] Mahmood NA, Haleh MO, Mohammad PO, Mohsen FA, Hossein KJ. Pathological changes of gentamicin in liver tissue and antioxidant property of Cinnamon extract on Wistar rats. Biomed Pharmacol J. 2014;7(1):341-7.
[47] Sharma A, Sharma V, Kansal L. Amelioration of lead-induced hepatotoxicity by Alliumsativum extracts in Swiss albino mice. Libyan journal of Medicine. 2010 Jan 1;5(1):4621.
[48] Stojiljkovic N and Stoiljkovic M. Micromorphological characteristics of the liver and biochemical analyses in the blood of rats treated by gentamicinand verapamil. Actamedica Medianae.2006a, 45(2):5-9.
[49] Stojiljkovic N and Stoiljkovic M. Micromorphological and histochemical characteristics of a rat’s liver treated with gentamicin. Acta medica Medianae.2006b, 45(3):24-28.
[50] Graw A, Cowan RA, O`Reilly DS, Stevant MJ, Stephard J. Clinical biochemistry-an illustrated color text. Is ted. New York: Churchill Livingstone. 1999:51-3.
[51] Khan MR, Badar I, Siddiquah A. Prevention of hepatorenal toxicity with Sonchusasper in gentamicin treated rats. BMC complementary and alternative medicine. 2011 Dec;11(1):113.