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Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu / Tam, Joseph

CiteScore 2016: 1.01

SCImago Journal Rank (SJR) 2016: 0.349
Source Normalized Impact per Paper (SNIP) 2016: 0.495

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Volume 29, Issue 1


Ameliorative effect of gallic acid on doxorubicin-induced cardiac dysfunction in rats

Temiday O. Omóbòwálé / Ademola A. Oyagbemi
  • Corresponding author
  • Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
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/ Ayorinde M. Folasire / Temitayo O. Ajibade
  • Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
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/ Ebunoluwa R. Asenuga
  • Department of Veterinary Physiology, Pharmacology and Biochemistry, University of Benin, Benin City, Nigeria
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/ Olumuyiwa A. Adejumobi / Olufunke E. Ola-Davies
  • Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
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/ Orotusin Oyetola / Gana James / Adeolu A. Adedapo / Momoh A. Yakubu
  • Department of Environmental and Interdisciplinary Sciences, College of Science, Engineering and Technology, Vascular Biology Unit, Center for Cardiovascular Diseases, COPHS, Texas Southern University, Houston, TX, USA
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Published Online: 2017-10-09 | DOI: https://doi.org/10.1515/jbcpp-2016-0194



The use of doxorubicin (DOX) as an antineoplastic agent has been greatly limited because of the myriad of toxic sequelae associated with it. The aim of this study was to assess the protective effects of gallic acid (GA) on DOX-induced cardiac toxicity in rats.


Sixty male rats (Wistar strain) were used in this study. They were divided into six groups (A–F) each containing 10 animals. Group A was the control. Rats in Groups B, C, and D were treated with DOX at the dosage of 15 mg/kg body weight i.p. Prior to this treatment, rats in Groups C and D had been treated orally with GA for 7 days at the dosage of 60 and 120 mg/kg, respectively. Animals from Groups E and F received only 60 and 120 mg/kg GA, respectively, which were administered orally for 7 days.


The exposure of rats to DOX led to a significant (p<0.05) decrease in the cardiac antioxidant defence system and elevation of creatine kinase myocardial band and lactate dehydrogenase. The electrocardiography results showed a significant decrease in heart rate, QRS, and QT-segment prolongation. GA alone improved the antioxidant defence system.


The GA pretreatment significantly alleviated GA-associated ECG abnormalities, restored the antioxidant status and prevented cardiac damage.

Keywords: antioxidant; cardiotoxicity; doxorubicin; electrocardiogram; gallic acid; serum biomarkers


  • 1.

    Räsänen M, Degerman J, Nissinen TA, Miinalainen I, Kerkelä R, Siltanen A, et al. VEGF-B gene therapy inhibits doxorubicin-induced cardiotoxicity by endothelial protection. Proc Natl Acad Sci USA 2016;113:13144–9.CrossrefGoogle Scholar

  • 2.

    Klippstein R, Bansal SS, Al-Jamal KT. Doxorubicin enhances curcumin’s cytotoxicity in human prostate cancer cells in vitro by enhancing its cellular uptake. Int J Pharm 2016;514:169–75.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 3.

    Prysyazhna O, Burgoyne JR, Scotcher J, Grover S, Kass D, Eaton P. Phosphodiesterase 5 inhibition limits doxorubicin-induced heart failure by attenuating protein kinase G Iα oxidation. J Biol Chem 2016;291:17427–36.CrossrefWeb of SciencePubMedGoogle Scholar

  • 4.

    Keeney JT, Miriyala S, Noel T, Moscow JA, St Clair DK, Butterfield DA. Superoxideinduces protein oxidation in plasma and TNF-α elevation in macrophage culture: insights into mechanisms of neurotoxicity following doxorubicin chemotherapy. Cancer Lett 2015;367:157–61.PubMedCrossrefGoogle Scholar

  • 5.

    Kwatra M, Kumar V, Jangra A, Mishra M, Ahmed S, Ghosh P, et al. Ameliorative effect of naringin against doxorubicin-induced acute cardiac toxicity in rats. Pharm Biol 2016;54:637–47.Web of ScienceCrossrefPubMedGoogle Scholar

  • 6.

    Injac R, Boskovic M, Perse M, Koprivec-Furlan E, Cerar A, Djordjevic A, et al. Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C60(OH)24 via suppression of oxidative stress. Pharmacol Rep 2008;60:742–9.PubMedGoogle Scholar

  • 7.

    Thandavarayan RA, Watanabe K, Sari FR, Ma M, Lakshmanan AP, Giridharan VV, et al. Modulation of doxorubicin-induced cardiac dysfunction in dominant-negative p38α mitogen-activated protein kinase mice. Free Radic Biol Med 2010;49:1422–31.Web of SciencePubMedCrossrefGoogle Scholar

  • 8.

    Nakai S. Myriophyllum spicatum- released allelopathic polyphenols inhibiting growth of blue-green algae Microcystis aeruginosa. Water Res 2000;34:3026–32.CrossrefGoogle Scholar

  • 9.

    Kim SH, Jun CD, Suk K, Choi BJ, Lim H, Park S, et al. Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells. Toxicol Sci 2006;91:123–31.CrossrefPubMedGoogle Scholar

  • 10.

    Akinrinde AS, Oyagbemi AA, Omobowale TO, Asenuga ER, Ajibade TO. Alterations in blood pressure, antioxidant status and caspase 8 expression in cobalt chloride-induced cardio-renal dysfunction is reversed by ocimum gratissimum and Gallic acid in Wistar rats. J Trace Elem Med Biol 2016;36:27–37.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 11.

    Oyagbemi AA, Omobowale TO, Saba AB, Olowu ER, Dada RO, Akinrinde AS. Gallic acid ameliorates cyclophosphamide-induced neurotoxicity in wistar rats through free radical scavenging activity and improvement in antioxidant defense system. J Diet Suppl 2016;13:402–19.PubMedCrossrefGoogle Scholar

  • 12.

    Calderon A, Barrios V, Escobar C, Ferrer E, Barrios S, González-Pedel V, et al. Detection of left ventricular hypertrophy by different electrocardiographic criteria in clinical practice. Findings from the sara study. Clin Exp Hypertens 2010;32:145–53.Web of ScienceCrossrefPubMedGoogle Scholar

  • 13.

    Green LC, Ruiz de Luzuriaga K, Wagner DA. Nitrate biosynthesis in man. Proc Natl Acad Sci USA 1981;78:7764–8.CrossrefGoogle Scholar

  • 14.

    Crespo E, Macías M, Pozo D, Escames G, Martín M, Vives F, et al. Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharide-induced multiple organ dysfunction syndrome in rats. FASEB J 1999;13:1537–46.PubMedGoogle Scholar

  • 15.

    Xia Y, Zweier JL. Measurement of myeloperoxidase in leukocyte-containing tissues. Anal Biochem 1997;245:93–6.CrossrefPubMedGoogle Scholar

  • 16.

    Sinha KA. Colorimetric assay of catalase. Anal Biochem 1972;47:389–94.CrossrefPubMedGoogle Scholar

  • 17.

    Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972;247:3170–5.Google Scholar

  • 18.

    Oyagbemi AA, Omobowale TO, Akinrinde AS, Saba AB, Ogunpolu BS, Daramola O. Lack of reversal of oxidative damage in renal tissues of lead acetate-treated rats. Environ Toxicol 2015;30:1235–43.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 19.

    Omobowale TO, Oyagbemi AA, Akinrinde AS, Saba AB, Daramola OT, Ogunpolu BS, et al. Failure of recovery from lead induced hepatoxicity and disruption of erythrocyte antioxidant defence system in wistar rats. Environ Toxicol Pharmacol 2014;37:1202–11.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 20.

    Habig, WH, Pabst, MJ, Jacoby WB. Glutathione-S-transferase activity: the enzymic step in mercapturic acid formation. J Biol Chem 1974;249:7130–9.Google Scholar

  • 21.

    Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882–8.PubMedGoogle Scholar

  • 22.

    Gay CA, Gebicki JM. Measurement of protein and lipid hydroperoxides in biological systems by the ferric-xylenol orange method. Anal Biochem 2003;315:29–35.PubMedCrossrefGoogle Scholar

  • 23.

    Olszewska-Słonina DM, Mątewski D, Czajkowski R, Olszewski KJ, Woźniak A, et al. The concentration of thiobarbituric acid reactive substances (TBARS) and paraoxonase activity in blood of patients with osteoarthrosis after endoprosthesis implantation. Med Sci Monit 2011;17:CR498–504.PubMedGoogle Scholar

  • 24.

    Wendel A, Fausel M, Safayhi H, Tiegs G, Otter R. A novel biologically active seleno-organic compound-II, activity of PZ 51 in relation to glutathione peroxidase. Biochem Pharmacol 1984;33:3200–41.Google Scholar

  • 25.

    Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70–7.CrossrefPubMedGoogle Scholar

  • 26.

    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265–75.PubMedGoogle Scholar

  • 27.

    Drury RA, Wallington EA, Cancerson R. Caltons histological techniques, 4th ed. UK: Oxford University Press, 1976.Google Scholar

  • 28.

    Menna P, Salvatorelli E, Minotti G. Anthracycline degradation in cardiomyocytes: a journey to oxidative survival. Chem ResToxicol 2010;23:6–10.Google Scholar

  • 29.

    You BR, Kim SZ, Kim SH, Park WH. Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis. Food Chem Toxicol 2010;48:1334–40.Web of ScienceCrossrefPubMedGoogle Scholar

  • 30.

    Ammar El-Sayed M, Shehta AS, Sally LE, Ghada MS. Cardioprotective effect of grape-seed proanthocyanidins on doxorubicin-induced cardiac toxicity in rats. Pharm Biol 2013;51:339–44.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 31.

    Padma VV, Poornima P, Prakash C, Bhavani R. Oral treatment with gallic acid and quercetin alleviates lindane-induced cardiotoxicity in rats. Can J Physiol Pharmacol 2013;91:134–40.Web of SciencePubMedCrossrefGoogle Scholar

  • 32.

    Chen R, Wang J, Zhang Y, Tang S, Zhan S. Key factors of susceptibility to antituberculosis drug-induced hepatotoxicity. Arch Toxicol 2015;89:883–97.CrossrefPubMedGoogle Scholar

  • 33.

    Beyerle J, Frei E, Stiborova M, Habermann N, Ulrich CM. Biotransformation of xenobiotics in the human colon and rectum and its association with colorectal cancer. Drug Metab Rev 2015;47:199–21.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 34.

    Nowakowska A, Tarasiuk J. Comparative effects of selected plant polyphenols, gallic acid and epigallocatechin gallate, on matrix metalloproteinases activity in multidrug resistant MCF7/DOX breast cancer cells. Acta Biochim Pol 2016;63:571–5.CrossrefWeb of SciencePubMedGoogle Scholar

  • 35.

    Panchuk RR, Lehka LV, Terenzi A, Matselyukh BP, Rohr J, Jha AK, et al. Rapid generation of hydrogen peroxide contributes to the complex cell death induction by the angucycline antibiotic landomycin E. Free Radic Biol Med 2017;106:134–47.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 36.

    Elberry AA, Abdel-Naim AB, Abdel-Sattar EA, Nagy AA, Mosli HA, Mohamadin AM, et al. Cranberry (Vaccinium macrocarpon) protects against doxorubicin-induced cardiotoxicity in rats. Food Chem Toxicol 2010;48:1178–84.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 37.

    Davies MJ. Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention. J Clin Biochem Nutr 2011;48:8–19.PubMedWeb of ScienceGoogle Scholar

  • 38.

    Shah SL, Mali VR, Zambare GN, Bodhankar SL. Cardioprotective activity of methanol extract of fruit of Trichosanthes cucumerina on doxorubicin-induced cardiotoxicity in Wistar rats. Toxicol Int 2012;19:167–72.CrossrefPubMedGoogle Scholar

  • 39.

    Shivakumar P, Rani MU, Reddy AG, Anjaneyulu Y. A study on the toxic effects of Doxorubicin on the histology of certain organs. Toxicol Int 2012;19:241–4.CrossrefPubMedGoogle Scholar

  • 40.

    Patel SS, Goyal RK. Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats. Pharmacog Res 2011;3:239–45.CrossrefGoogle Scholar

About the article

Corresponding author: Dr. Ademola A. Oyagbemi, DVM, PhD, FCVSN, Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria, Phone: +234833639776, Fax: +028103043; email:

Received: 2016-12-27

Accepted: 2017-07-23

Published Online: 2017-10-09

Published in Print: 2018-01-26

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 29, Issue 1, Pages 19–27, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2016-0194.

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