Skip to main content
SpringerLink
Log in

Antiarrhythmic effects and ionic mechanisms of allicin on myocardial injury of diabetic rats induced by streptozotocin

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

The aim of this study was to evaluate the antiarrhythmic effect of allicin (AL) on streptozotocin (STZ)-induced diabetic rats and explore the possible mechanisms. Hyperglycemia was induced in rats by single intraperitoneal injection of STZ (40 mg/kg). Three days after STZ treatment, the hyperglycemic rats (plasma glucose levels ≥16.7 mM) were administered with AL (4, 8, and 16 mg/kg) by intraperitoneal injection daily for 28 days. The fasting blood glucose levels were measured on every seventh day during the 28 days of treatment. The body weight and blood glucose levels were detected after 28 days. Antiarrhythmic effect of AL was observed in the diabetic rats induced by BaCl2. To determine the ionic mechanism in rat ventricular myocytes of AL, action potential duration (APD), L-type calcium current (ICa-L), and inward rectifier potassium current (IK1) were recorded by the whole cell-patch clamp technique. The expressions of L-type calcium channel protein α1C mRNA and cell potassium channels protein Kir2.1 mRNA were studied by RT-PCR. AL normalized the RR interval and QT interval in diabetic rats. AL obviously delayed the onset of ventricular arrhythmia and reduced the score of arrhythmia induced by BaCl2. Electrophysiological experiment revealed that AL could shorten APD through inhibition of ICa-L and enhancement of IK1. RT-PCR analysis indicated that long-term treatment with AL could decrease the expression of α1C mRNA and increase the expression of Kir2.1 mRNA. AL has antiarrhythmic effect in STZ-induced diabetic rats. It is tempting for the application of AL to be a useful therapeutic approach in diabetes with ventricular arrhythmia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

AL:

Allicin

STZ:

Streptozotocin

APD:

Action potential duration

ICa-L :

L-type calcium current

IK1 :

Inward rectifier potassium current

DCM:

Diabetes cardiomyopathy

RyR:

Ryanodine receptor

SR:

Sarcoplasmic reticulum

PVC:

Premature ventricular contraction

VT:

Ventricular tachycardia

VF:

Ventricular fibrillation

SNK:

Student–Newman–Keuls

References

  • Asghar O, Al-Sunni A, Khavandi K et al (2009) Diabetic cardiomyopathy. Clin Sci 116:741–760

    Article  PubMed  CAS  Google Scholar 

  • Banerjee SK, Maulik SK (2002) Effect of garlic on cardiovascular disorders: a review. Nutr J 1:4

    Article  PubMed  Google Scholar 

  • Bers DM (2002) Cardiac excitation–contraction coupling. Nature 415:198–205

    Article  PubMed  CAS  Google Scholar 

  • Bertoni AG, Hundley WG, Massing MW et al (2004) Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care 27:699–703

    Article  PubMed  Google Scholar 

  • Block E (1985) The chemistry of garlic and onions. Sci Am 252:114–119

    Article  PubMed  CAS  Google Scholar 

  • Carmeliet E (1999) Cardiac ionic currents and acute ischemia: from channels to arrhythmias. Physiol Rev 79:917–1017

    PubMed  CAS  Google Scholar 

  • Chilton L, Ohya S, Freed D et al (2005) K+ currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts. Am J Physiol Heart Circ Physiol 288:H2931–H2939

    Article  PubMed  CAS  Google Scholar 

  • Chung LY (2006) The antioxidant properties of garlic compounds: allyl cysteine, alliin, allicin, and allyl disulfide. Journal of medicinal food 9:205–213

    Article  PubMed  CAS  Google Scholar 

  • Clancy CE, Kass RS (2002) Defective cardiac ion channels: from mutations to clinical syndromes. J Clin Invest 110:1075–1077

    PubMed  CAS  Google Scholar 

  • Deshpande AD, Harris-Hayes M, Schootman M (2008) Epidemiology of diabetes and diabetes-related complications. Phys Ther 88:1254–1264

    Article  PubMed  Google Scholar 

  • Dhamoon AS, Jalife J (2005) The inward rectifier current (IK1) controls cardiac excitability and is involved in arrhythmogenesis. Hear Rhythm 2:316–324

    Article  Google Scholar 

  • Diaz RJ, Zobel C, Cho HC et al (2004) Selective inhibition of inward rectifier K+ channels (Kir2.1 or Kir2.2) abolishes protection by ischemic preconditioning in rabbit ventricular cardiomyocytes. Circ Res 95:325–332

    Article  PubMed  CAS  Google Scholar 

  • Ginter E, Simko V (2010) Garlic (Allium sativum L.) and cardiovascular diseases. Bratisl Lek List 111:452–456

    CAS  Google Scholar 

  • Hasan N, Yusuf N, Toossi Z et al (2006) Suppression of Mycobacterium tuberculosis induced reactive oxygen species (ROS) and TNF-alpha mRNA expression in human monocytes by allicin. FEBS Lett 580:2517–2522

    Article  PubMed  CAS  Google Scholar 

  • Hove-Madsen L, Llach A, Bayes-Genís A et al (2004) Atrial fibrillation is associated with increased spontaneous calcium release from the sarcoplasmic reticulum in human atrial myocytes. Circulation 110:1358–1363

    Article  PubMed  CAS  Google Scholar 

  • Jalife J (2000) Ventricular fibrillation: mechanisms of initiation and maintenance. Annu Rev Physiol 62:25–50

    Article  PubMed  CAS  Google Scholar 

  • Li GR, Lau CP, Ducharme A et al (2002) Transmural action potential and ionic current remodeling in ventricles of failing canine hearts. Am J Physiol Heart Circ Physiol 283:H1031–H1041

    PubMed  CAS  Google Scholar 

  • Liu Y, Sun HL, Li DL et al (2008) Choline produces antiarrhythmic actions in animal models by cardiac M3 receptors: improvement of intracellular Ca2+ handling as a common mechanism. Can J Physiol Pharmacol 86:860–865

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Qi H, Wang Y et al (2012) Allicin protects against myocardial apoptosis and fibrosis in streptozotocin-induced diabetic rats. Phytomedicine 19:693–698

    Article  PubMed  CAS  Google Scholar 

  • Martín N, Bardisa L, Pantoja C et al (1994) Anti-arrhythmic profile of a garlic dialysate assayed in dogs and isolated atrial preparations. J Ethnopharmacol 43:1–8

    Article  PubMed  Google Scholar 

  • Mest HJ, Förster W (1979) The central nervous effect of prostaglandins I2, E2 and F2 alpha on aconitine-induced cardiac arrhythmia in rats. Prostaglandins 18:235–239

    Article  PubMed  CAS  Google Scholar 

  • Neef S, Dybkova N, Sossalla S et al (2010) CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation. Circ Res 106:1134–1144

    Article  PubMed  CAS  Google Scholar 

  • Rose J, Armoundas AA, Tian Y et al (2005) Molecular correlates of altered expression of potassium currents in failing rabbit myocardium. Am J Physiol Heart Circ Physiol 288:H2077–H2087

    Article  PubMed  CAS  Google Scholar 

  • Shao CH, Capek HL, Patel KP et al (2011) Carbonylation contributes to SERCA2a activity loss and diastolic dysfunction in a rat model of type 1 diabetes. Diabetes 60:947–959

    Article  PubMed  CAS  Google Scholar 

  • Shao CH, Wehrens XH, Wyatt TA et al (2009) Exercise training during diabetes attenuates cardiac ryanodine receptor dysregulation. J Appl Physiol 106:1280–1292

    Article  PubMed  CAS  Google Scholar 

  • Sungnoon R, Kanlop N, Chattipakorn SC et al (2008) Effects of garlic on the induction of ventricular fibrillation. Nutrition 24:711–716

    Article  PubMed  CAS  Google Scholar 

  • Sun HL, Chu WF, Dong DL et al (2006) Choline-modulated arsenic trioxide-induced prolongation of cardiac repolarization in Guinea pig. Basic & Clinical Pharmacology & Toxicology 98:381–388

    Article  CAS  Google Scholar 

  • Tomaselli GF, Beuckelmann DJ, Calkins HG et al (1994) Sudden cardiac death in heart failure. The role of abnormal repolarization. Circulation 90:2534–2539

    Article  PubMed  CAS  Google Scholar 

  • Voigt N, Li N, Wang Q et al (2012) Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+-Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation. Circulation 125:2059–2070

    Article  PubMed  CAS  Google Scholar 

  • Xu C, Lu Y, Pan Z et al (2007) The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. Journal of cell science 120:3045–3052

    Article  PubMed  CAS  Google Scholar 

  • Yaras N, Ugur M, Ozdemir S et al (2005) Effects of diabetes on ryanodine receptor Ca2+ release channel (RyR2) and Ca2+ homeostasis in rat heart. Diabetes 54:3082–3088

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Project of Science & Technology Bureau of Daqing of China (SGG2008-048).

Author information

Authors and Affiliations

  1. Department of Pharmacology, Harbin Medical University—Daqing, Daqing, Heilongjiang, 163319, China

    Wei Huang, Ye Wang, Yong-Gang Cao, Han-Ping Qi & Hong-Li Sun

  2. Department of Surgery, Fifth Clinical College, Harbin Medical University, Daqing, Heilongjiang, 163316, China

    Lei Li

  3. Department of Biology, Harbin Medical University—Daqing, Daqing, Heilongjiang, 163319, China

    Bing Bai

  4. Department of Basic Nursing, Harbin Medical University—Daqing, Daqing, Heilongjiang, 163319, China

    Yang Liu

Authors
  1. Wei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ye Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong-Gang Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Han-Ping Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bing Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hong-Li Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hong-Li Sun.

Additional information

Wei Huang and Ye Wang made equal contribution to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, W., Wang, Y., Cao, YG. et al. Antiarrhythmic effects and ionic mechanisms of allicin on myocardial injury of diabetic rats induced by streptozotocin. Naunyn-Schmiedeberg's Arch Pharmacol 386, 697–704 (2013). https://doi.org/10.1007/s00210-013-0872-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-013-0872-1

Keywords

Search

Navigation