p-Coumaric acid attenuates apoptosis in isoproterenol-induced myocardial infarcted rats by inhibiting oxidative stress

https://doi.org/10.1016/j.ijcard.2013.04.138Get rights and content

Abstract

Background

Cardiac apoptosis plays an important role in the pathology of myocardial infarction. The protective effects of p-coumaric acid on cardiac apoptosis were evaluated in isoproterenol induced myocardial infarcted rats.

Methods

Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days. After pretreatment, isoproterenol (100 mg/kg body weight) was injected subcutaneously into rats at an interval of 24 h for 2 days to induce myocardial infarction. Cardiac diagnostic markers, heart lipid peroxidation, antioxidant system, histopathological changes of the heart and apoptosis were evaluated in isoproterenol induced myocardial infarcted rats.

Results

Isoproterenol induced myocardial infarcted rats showed a significant increase in the levels of serum cardiac diagnostic markers, heart lipid peroxidation products and a significant decrease in the activities/levels of heart antioxidants. Histopathological findings of myocardial infarcted rats revealed marked necrosis and edema. Reverse Transcription Polymerase Chain Reaction study revealed an increase in the myocardial expression of Bax, caspase-8, caspase-9 and Fas genes and a decrease in the myocardial expression of Bcl-2 and Bcl-xL genes. p-Coumaric acid pretreatment showed protective effects on apoptosis by inhibiting oxidative stress. p-Coumaric acid pretreated isoproterenol induced myocardial infarcted heart also confirmed these findings. The possible mechanisms for the protective effects of p-coumaric acid could be attributed to antilipid peroxidative, antioxidant and antiapoptotic properties.

Conclusion

Thus, p-coumaric acid protected the myocardial infarcted rat's heart against apoptosis by inhibiting oxidative stress.

Introduction

According to the world health organization, over 80% of cardiovascular diseases take place in low and middle income countries. Myocardial infarction (MI) is the irreversible necrosis of heart muscle secondary to prolonged ischemia that results from an imbalance between coronary blood supply and myocardial demand. Isoproterenol (ISO), a synthetic catecholamine, causes severe stress in the myocardial tissue and its high dose produces myocardial injury in rats as a result of disturbance in physiological balance between the production of free radicals and antioxidant defense system [1]. It is the acute condition of myocardial necrosis which causes impaired cardiac function, elevated levels of cardiac diagnostic markers, increased lipid peroxidation and decreased antioxidant system [2]. ISO-induced myocardial necrosis involves membrane permeability alterations that bring about the loss of function and integrity of myocardial membranes [3]. MI induced by ISO has been reported to show many morphological and metabolic aberrations in the heart tissue of experimental animals similar to those observed in human MI [4].

Dietary factors play an important role in preventing human diseases. Epidemiological studies have shown that diets rich in herbs, fruits and spices reduce the risk of cardiovascular diseases [5]. p-Coumaric acid is a phenolic acid, widely distributed in plants and form a part of human diet [6]. It is widely present in fruits such as apples, pears and also in vegetables and plant products such as beans, potatoes, tomatoes and tea. Also, p-coumaric acid is abundantly present in pineapple. It has been found to reduce the risk of stomach cancer [7] by reducing the formation of carcinogenic nitrosamines [8].

In the myocardium, apoptosis has been observed in a number of cardiac pathologies including hypoxia, ischemia followed by reperfusion, MI, myocardial hypertrophy and in patients with end-stage heart failure [9]. Evidence has accumulated that oxidative stress activates multiple cell signaling pathways, including the apoptotic pathways [10]. Activation of the apoptotic pathways in the heart may lead to contractile dysfunction prior to cell death. Since apoptosis is implicated in the pathogenesis of MI, the inhibition of apoptosis promises to be a potent target for the treatment of MI. During reperfusion, cardiomyocyte apoptosis occurs at a high rate during a defined time period. Thus, a short-term pretreatment is highly effective. The concept of early therapeutic interference with acute pretreatment to prevent MI and heart failure is extremely attractive. Literature survey has shown that there are no scientific reports available on the effects of p-coumaric acid on apoptosis in MI. Hence, this manuscript addresses the protective effects of p-coumaric acid in ISO induced apoptosis in rats.

Section snippets

Experimental animals

All the experiments were carried out with male albino Wistar rats weighing 170–200 g, obtained from The Central Animal House, Rajah Muthiah Institute of Health Sciences, Annamalai University, Tamil Nadu, India. They were housed in polypropylene cages (47 × 34 × 20 cm) lined with husk, renewed every 24 h under a 12:12 h light/dark cycle at around 22 °C. The rats had free access to tap water and food. The rats were fed on a standard pellet diet (Pranav Agro Industries Ltd., Maharashtra, India). The

Effect of p-coumaric acid on the activity of serum CK-MB (Dose dependent study)

A pilot study was performed with three different doses of p-coumaric acid (2, 4 and 8 mg/kg body weight) to determine the dose dependent effect and the duration of pretreatment of p-coumaric acid in the ISO induced (on 8th and 9th day) myocardial infarcted rats. We examined the activity of cardiac marker enzyme, serum CK-MB in the rats pretreated with p-coumaric acid (2, 4 and 8 mg/kg body weight) in the myocardial infarcted rats. We observed near normalized activity of serum CK-MB when compared

Discussion

A dose dependent study was performed with three different doses of p-coumaric acid (2, 4 and 8 mg/kg body weight) on serum CK-MB activity in the ISO induced myocardial infarcted rats. ISO causes an increase in the activity of diagnostic marker enzyme, CK-MB. The increased activity of CK-MB in serum might be due to ISO-induced myocardial necrosis. Pretreatment with p-coumaric acid (2, 4 and 8 mg/kg body weight) daily for a period of 7 days dose dependently decreased the elevated activity of serum

Conclusions

In conclusion, the biochemical, histological and RT-PCR findings observed from our study indicate that p-coumaric acid offers protection to the myocardium against ISO induced apoptosis in Wistar rats. p-Coumaric acid inhibits oxidative stress, thereby attenuating apoptosis in the myocardial infarcted rats. The observed protective effects of p-coumaric acid could be attributed to antilipid peroxidative, antioxidant and antiapoptotic properties. Thus, the findings of this study may be beneficial

Acknowledgements

The authors are grateful to Dr. C.S. Vijayalakshmi, MD, Consultant Pathologist, Vaishnavi Histopathology and Cytology Centre, Chrompet, Chennai, Tamil Nadu for carrying out the histopathology of heart and its interpretation. We also thank Dr. Philomena Mariadoss, Ph.D., Dean, Madras Medical Mission, College of Health Sciences, Chennai, Tamil Nadu for permitting to perform RT-PCR study in the Department of Genetics.

The authors of this manuscript have certified that they comply with the

References (39)

  • O.H. Lowry et al.

    Protein measurement with Folin-phenol reagent

    J Biol Chem

    (1951)
  • T.S. Manjula et al.

    Effect of aspirin on lipid peroxidation in experimental myocardial infarction in rats

    J Nutr Biochem

    (1994)
  • G. Polidoro et al.

    Superoxide dismutase, reduced glutathione and thiobarbituric acid reactive products in erythrocytes of patients with multiple sclerosis

    Int J Biochem

    (1984)
  • G. Saravanan et al.

    Effect of garlic (Allium sativum) on lipid peroxidation in experimental myocardial infarction in rats

    J Ethnopharmacol

    (2004)
  • F. Wernig et al.

    Mechanical stress-induced apoptosis in the cardiovascular system

    Prog Biophys Mol Biol

    (2002)
  • C. Nirmala et al.

    Protective role of curcumin against isoproterenol induced myocardial infarction in rats

    Mol Cell Biochem

    (1996)
  • S.K. Banerjee et al.

    Effect of garlic on cardiovascular disorders: a review

    J Nutr

    (2002)
  • L.R. Ferguson et al.

    Antioxidant and antigenotoxic effects of plant cell wall hydroxycinnamic acids in cultured HT-29 cells

    Mol Nutr Food Res

    (2005)
  • K. Kikugawa et al.

    Reaction of p-hydroxycinnamic acid derivatives with nitrite and its relevance to nitrosamine formation

    J Agric Food Chem

    (1983)
  • Cited by (57)

    • A pharmacokinetic-pharmacodynamic study to elucidate the cardiovascular protective constituents in Danhong Injection

      2022, Journal of Pharmaceutical and Biomedical Analysis
      Citation Excerpt :

      These compounds include salvianolic acid B, rosmarinic acid, p-coumaric acid, salvianolic acid A, danshensu, cytidine, uridine, caffeic acid, protocatechuic acid, and ferulic acid, consistent with previous reports [23–25]. In addition, all the 10 compounds had been reported to possess cardiovascular protective effects [26–32]. Thus, we studied the PK of these compounds in rats plasma to establish the PK-PD correlation.

    View all citing articles on Scopus
    View full text