The cardioprotective effect of vanillic acid on hemodynamic parameters, malondialdehyde, and infarct size in ischemia-reperfusion isolated rat heart exposed to PM10

Document Type: Original Article


1 Physiology Research Center and Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Department of Environmental Health Engineering, Health Faculty, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran


Objective(s): Particulate matter (PM) exposure can promote cardiac ischemia and myocardial damage. The effects of PM10 on hemodynamic parameters, lipid peroxidation, and infarct size induced by ischemia-reperfusion injury and the protective effects of vanillic acid (VA) in isolated rat heart were investigated.
Materials and Methods: Eighty male Wistar rats (250–300 g) were divided into 8 groups (n=10): Control, Sham, VAc, VA, PMa (0.5 mg/kg PM, intratracheal instillation), PMb (2.5 mg/kg PM, intratracheal instillation), PMc (5 mg/kg PM, intratracheal instillation), and PMc + VA (5 mg/kg PM, intratracheal instillation; and 10 mg/kg vanillic acid, gavage for 10 days). PM10 was instilled into the trachea in two stages, within 48 hr. After isolating the hearts and transfer to a Langendorff apparatus, hearts were subjected to 30 min ischemia and 60 min reperfusion. Hemodynamic parameters (±dp/dt, LVSP, LVDP, and RPP), production of lipid peroxidation (MDA), and infarct size were assessed.
Results: A significant decrease in ±dp/dt, LVSP, LVDP and RPP occurred in PM groups. A significant increase in MDA and myocardial infarct size occurred in PM groups. A significant increase in LVDP, LVSP, ±dp/dt, RPP and decrease in infarct size, MDA, and myocardial dysfunction was observed in groups that received vanillic acid after ischemia–reperfusion.
Conclusion: It was demonstrated that PM10 increases MDA, as well as the percentage of cardiac infarct size, and has negative effects on hemodynamic parameters. This study suggests that vanillic acid may serve as an adjunctive treatment in delaying the progression of ischemic heart disease.


1. Canbaz S, Duran E, Ege T, Sunar H, Cikirikcioglu M, Acipayam M. The effects of intracoronary administration of vitamin E on myocardial ischemia-reperfusion injury during coronary artery surgery. Thorac Cardiovasc Surg 2003; 51:57–61.

2. Kinugasa Y, Ogino K, Furuse Y, Shiomi T, Tsutsui H, YamamotoT, et al. Allopurinol improves cardiac dysfunction after ischemia-reperfusion via reduction of oxidative stress in isolated perused rat hearts. Circ J 2003;  67:781–82.

3. Dhalla NS, Elmoselhi AB, Hata T, Makino, N. Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovasc Res 2000; 47:446-456..

4. Holland NA, Fraiser CR, Sloan RC 3rd, Devlin RB, Brown DA, Wingard CJ. Ultrafine particulate matter increases cardiac ischemia/reperfusion injury via mitochondrial permeability transition pore. Cardiovasc Toxicol 2017; doi: 10.1007/s12012-017-9402-6.

5. Cozzi E, Hazarika S, Stallings HW 3rd, Cascio WE, Devlin RB, Lust RM, et al. Ultrafine particulate matter exposure augments ischemia-reperfusion injury in mice. Am J Physiol Heart Circ Physiol 2006; 291:H894-903.

6. Du Y, Xu X, Chu M, Guo Y, Wang J. Air particulate matter and cardiovascular disease: the epidemiological, biomedical and clinical evidence. J Thorac Dis 2016; 8:E8-e19.

7. Brook  RD, Rajagopalan S, PopeC A 3rd, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, et al. Particulate matter air pollution and cardiovascular disease an update to the scientific statement from the american heart association. Circulation 2010; 121:2331-2378. 

8. Pope CA 3rd, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, Godleski JJ. Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation 2004; 109:71–77.

9. Bajpai R,Mishra G K, Mohabe S, Upreti D K, Nayaka S. Determination of atmospheric heavy metals using two lichen species in Katni and Rewa cities, India. J Environ Biol 2011; 32:195-159. 

10. Goudarzi GH, Zallaghi E, Neissi A, Ahmadi Ankali K, Sakid A, Babaeia A, et al. Cardiopulmonary mortalities and chronic obstructive pulmonary disease attributed to ozone air pollution. Arch Hyg Sci 2013;  2:62-72.

11. Goudarzi GH, Shirmardi M, Khodarahmi F, Hashemi-Shahraki A, Alavi N, AhmadiAnkali K, et al. Particulate matter and bacteria characteristics of the Middle East Dust (MED) storms over Ahvaz, Iran. Aerobiologia 2014; 30:345–356.

12. Singh G, Rohilla A, Singh M, Balakumar P. Possible role of JAK-2 in attenuated cardioprotective effect of ischemic preconditioning in hyper homocysteinemic rat hearts. Yakugaku Zasshi 2009; 129:523-535.

13. Lirdprapamongkol K, Sakurai H, KawasakiN,Choo MK, Saitoh Y, AozukaY. Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast cancer cells. Eur J Pharm Sci 2005;  25:57-65.

14. Chou TH, Ding HY,Hung WJ, Liang CH. Antioxidative characteristics and inhibition of α-melanocyte-stimulating hormone-stimulated melanogenesis of vanillin and vanillic acid from Origanumvulgare. Exp Dermatol 2010; 19:742-750.

15. Lirdprapamongkol K, Kramb JP, Suthiphongchai T, Surarit R, Srisomsap C, Dannhardt G, et al. Vanillin suppresses metastatic potential of human cancer cells through PI3K inhibition and decreases angiogenesis in vivo." Agric Food Chem 2009; 57:3055-3063..

16. Hegab MM, Ghareib HR. Antioxidative effects of acetone fraction and vanillic acid from Chenopodium murale L. on tomato plant. Weed Biol Manag 2010; 10:64-72.

17. Dianat M, Hamzavi GH, Badavi M, Samarbafzadeh  A. Effects of Losartan and vanillic acid co-administration on ischemia-reperfusion-induced oxidative stress in isolated rat heart. Iran Red Crescent Med J 2014; 16:e16664: 1-7.

18. Golomb E, Matza D, Cummings CA, Schwalb  H, Kodavanti UP, Schneider A, et al. Myocardial mitochondrial injury induced by pulmonary exposure to particulate matter in rats. Toxicol Pathol 2012; 40:779-788.

19. Goudie AS. Desert dust and human health disorders. Environ Int 2014; 63:101-113.

20. Heidari-Farsani M, Shirmardi M, Goudarzi GH, Alavi-Bakhtiarivand N, Ahmadi-Ankali K, Zallaghi E. The evaluation of heavy metals concentration related to PM10 in ambient air of Ahvaz city, Iran. J Adv Environ Health Res 2014;  1:120-128.

21. Hoffmann C, Funk R, Wieland  R,  Li Y, Sommer M. Effects of grazing and topography on dust flux and deposition in the Xilingele grassland, Inner Mongolia." J Arid Environ 2008;72:792-807.

22. Shahsavani A, Naddafi K, Jaafarzadeh HN, Mesdaghinia A, Yunesian M, Nabizadeh R, et al. Characterization of ionic composition of TSP and PM10 during the Middle Eastern Dust (MED) storms in Ahvaz, Iran. Environ Monit Assess 2012; 184:6683-6692.

23. Zhang W, Zhuang G, Guo J, Xu D, Wang W, Baumgardner D et al. Sources of aerosol as determined from elemental composition and size distributions in Beijing. Atmos Res 2010; 95:197-209.

24. Mohd TN, Poh SC, Suratman S, Ariffin MM, Shazali NA, Yunus K. Determination of trace metals in air borne particulate matter of Kuala Terengganu, Malaysia. Bull Environ ContamToxicol 2009; 83:199-203.

25. Manzano-Leon N, Quintana R, Sanchez B, Serrano J, Vega E, Vazquez-Lopez I, et al. Variation in the composition and in vitro pro inflammatory effect of urban particulate matter from different sites. J Biochem Mol Toxicol 2013; 27:87–97.

26. Kodavanti UP, Schladweiler MC, Gilmour PS, Wallenborn JG, Mandavilli BS, Ledbetter AD, et al. The role of particulate matter-associated zinc in cardiac injury in rats." Environ Health 2008; 116:13-20.

27.  Dianat M, Esmaeilizadeh M, Badavi M, Samarbafzadeh A, Naghizadeh B. Protective effects of crocin on hemodynamic parameters and infarct size in comparison with vitamin E after ischemia reperfusion in isolated rat hearts. Planta Med 2014a; 80:393–398.

28. Garcia-Villalon AL, Monge L, Fernandez N, Salcedo A. Coronary response to di adenosine penta phosphate after ischaemia–reperfusion in the isolated rat heart. Cardiovasc Res  2009; 81:336–343.

29. Price AN, Cheung KK, Lim, SY, Yellon DM, Hausenloy DJ , Lythgoe MF. Rapid assessment of myocardial infarct size in rodents using multi-slice inversion recovery late gadolinium enhancement CMR at 9.4T." J Cardiovasc Magn Reson 2011; 13:44.

30. Osada M, Netticadan T, Tamura K, Dhalla NS. Modification of ischemia reperfusion induced changes in cardiac sarcoplasmic reticulum by preconditioning. Am J Physiol 1998; 274:2025–2034.

31. Bagate K, Meiring JJ, Gerlofs-Nijland ME, Cassee FR, Wiegand H, Osornio-Vargas A, Borm PJA. Ambient particulate matter affects cardiac recovery in a langendorff ischemia model. Inhal Toxicol 2006; 18:633-643.

32. Cozzi E, Hazarika S, Stallings HW 3rd, Cascio WE, Devlin RB, Lust RM, et al. Ultrafine particulate matter exposure augments ischemia-reperfusion injury in mice. Am J Physiol Heart Circ Physiol 2006; 291:H894–H903.

33. Pope CA, Muhlestein JB, May HT, Renlund DG, Anderson JL, Horne BD. Ischemic heart disease events triggered by short term exposure to fine particulate air pollution. Circulation 2006;   114:2443–2448.

34. Brook RD, Rajagopalan S. Particulate matter air pollution and atherosclerosis.  Curr Atheroscler Rep 2010; 12:291–300.

35. Delfino RJ, Sioutas C, Malik S. Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health. Environ Health Perspect 2005; 113:934–946.

36. Soleimani Z, Parhizgari N, Dehdari Rad H, Akhoond MR, Kermani M, Bagherian M, et al. Normal and dusty days comparison of culturable indoor airborne bacteria in Ahvaz, Iran. Aerobiologia 2015;  31:127-141.

37. Robards K, Prenzler PD, Tucker G, Swatsitang P, Glover W. Phenolic compounds and their role in oxidative processes in fruits. Food Chem 1999; 66:401–436.

38. Natella F, Nardini M, Di Felice M, Saccini C. Benzoic and cinnamic acid derivatives as antioxidants: structure– activity relation. J Agric Food Chem 1999; 47:1453–1459.

39. Silva FA, Borges F, Guimaraes C, Lima JL, Matos C, Reis S. Phenolic acids and derivatives: studies on the relationship among structure, radical scavenging activity and physicochemical parameters. J Agric Food Chem 2000; 48:2122–2126.

40. Stanely Mainzen Prince P, Rajakumar S, Dhanasekar K. Protective effects of vanillic acid on electrocardiogram, lipid peroxidation, antioxidants, proinflammatory markers and histopathology in isoproterenol induced cardiotoxic rats. Eur J Pharmacol 2011; 668:233-240.