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α-Bisabolol abrogates isoproterenol-induced myocardial infarction by inhibiting mitochondrial dysfunction and intrinsic pathway of apoptosis in rats

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Abstract

Mitochondrial dysfunction plays crucial role in the pathologenesis of myocardial infarction (MI). The present study evaluated the protective effect of α-bisabolol against isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. Male albino Wistar rats were pre- and co-treated with intraperitoneal injection of α-bisabolol (25 mg/kg body weight) daily for 10 days. To induce experimental MI, ISO (85 mg/kg body weight) was injected subcutaneously to the rats at an interval of 24 h for 2 days (9th and 10th day). ISO-induced MI was indicated by the decreased activities of heart creatine kinase and lactate dehydrogenase in rats. ISO administration also enhanced the concentrations of heart mitochondrial lipid peroxidation products and decreased the activities/concentrations of mitochondrial antioxidants, Kreb’s cycle dehydrogenases and mitochondrial electron transport chain complexes I, II + III and IV in rats. Furthermore, ISO triggers calcium overload and ATP depletion in the rat’s heart mitochondria followed by the mitochondrial cytochrome-C release and the activation of intrinsic pathway of apoptosis by upregulating the myocardial pro-apoptotic Bax, P53, APAF-1, active caspase-3, active caspase-9 and down regulating the expressions of anti-apoptotic Bcl-2. α-Bisabolol pre and co-treatment showed considerable protective effects on all the biochemical and molecular parameters studied. Transmission electron microscopic study and mitochondrial swelling assay confirmed our biochemical and molecular findings. The in vitro study on hydroxyl radical also revealed the potent free radical scavenging activity of α-bisabolol. Thus, α-bisabolol attenuates mitochondrial dysfunction and intrinsic pathway of apoptosis in ISO-induced myocardial infarcted rats.

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Abbreviations

ISO:

Isoproterenol

MI:

Myocardial infarction

ATP:

Adenosine triphosphate

Bax:

B-cell lymphoma-2 associated-x

APAF-1:

Apoptotic protease activating factor 1

Bcl-2:

B-cell lymphoma-2

ETC:

Electron transport chain

ROS:

Reactive oxygen species

TCA:

Tricarboxylic acid

Ca2+ :

Calcium

CK:

Creatine kinase

LDH:

Lactate dehydrogenase

TBARS:

Thiobarbituric acid reactive substances

LOOH:

Lipid hydroperoxide

SOD:

Superoxide dismutase

GSH:

Reduced glutathione

ICDH:

Isocitrate dehydrogenase

MDH:

Malate dehydrogenase

SDH:

Succinate dehydrogenase

α-KGDH:

α-Ketoglutarate dehydrogenase

TEM:

Transmission electron microscopy

OH :

Hydroxyl radical

DMRT:

Duncan’s multiple range test

SPSS:

Statistical Package for the Social Science

SD:

Standard deviation

NAD:

Nicotinamide adenine dinucleotide

NADH:

Reduced nicotinamide adenine dinucleotide

NADP:

Nicotinamide adenine dinucleotide phosphate

References

  1. Nagoor Meeran MF, Jagadeesh GS, Selvaraj P (2015) Catecholamine toxicity triggers myocardial membrane destabilization in rats: thymol and its counter action. RSC Adv 5:43338–43344. https://doi.org/10.1039/C5RA00903K

    Article  CAS  Google Scholar 

  2. Hansi Priscilla D, Stanely Mainzen Prince P (2009) Cardioprotective effect of gallic acid on cardiac troponin-T, cardiac marker enzymes, lipid peroxidation products and antioxidants in experimentally induced myocardial infarction in Wistar rats. Chem Biol Interact 179:118–124. https://doi.org/10.1016/j.cbi.2008.12.012

    Article  CAS  PubMed  Google Scholar 

  3. Sivakumar R, Anandh Babu PV, Shyamaladevi CS (2008) Protective effect of aspartate and glutamate on cardiac mitochondrial function during myocardial infarction in experimental rats. Chem Biol Interact 176:227–233. https://doi.org/10.1016/j.cbi.2008.08.008

    Article  CAS  PubMed  Google Scholar 

  4. Xiang YK (2011) Compartmentalization of β-adrenergic signals in cardiomyocytes. Circ Res 109:231–244. https://doi.org/10.1161/CIRCRESAHA.110.231340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Xu Q, Dalic A, Fang L et al (2011) Myocardial oxidative stress contributes to transgenic β2-adrenoceptor activation-induced cardiomyopathy and heart failure. Br J Pharmacol 252:1012–1028. https://doi.org/10.1111/j.1476-5381.2010.01043.x

    Article  CAS  Google Scholar 

  6. Hemalatha KL, Stanely Mainzen P, Prince (2016) Preventive effects of zingerone on cardiac mitochondrial oxidative stress, calcium ion overload and adenosine triphosphate depletion in isoproterenol induced myocardial infarcted rats. RSC Adv 6:12332. https://doi.org/10.1039/C6RA23330A

    Article  CAS  Google Scholar 

  7. Nagoor Meeran MF, Jagadeesh GS, Selvaraj P (2015) Thymol attenuates altered lipid metabolism in β-adrenergic agonist induced myocardial infarcted rats by inhibiting tachycardia, altered electrocardiogram, apoptosis and cardiac hypertrophy. J Funct Foods 14:51–62. https://doi.org/10.1016/j.jff.2015.01.013

    Article  CAS  Google Scholar 

  8. Nagoor Meeran MF, Stanely Mainzen Prince P, Hidhayath Basha R (2012) Preventive effects of N-acetyl cysteine on lipids, lipoproteins and myocardial infarct size in isoproterenol induced myocardial infarcted rats: an in vivo and in vitro study. Eur J Pharmacol 677:116–122. https://doi.org/10.1016/j.ejphar.2011.11.043

    Article  CAS  PubMed  Google Scholar 

  9. Nagoor Meeran MF, Stanely Mainzen Prince P (2012) Protective effects of N-acetyl cysteine on membrane-bound adenosine triphosphatases and minerals in isoproterenol-induced myocardial-infarcted rats: an in vivo and in vitro study. J Biochem Mol Toxicol 26:276–281. https://doi.org/10.1002/jbt.21419

    Article  CAS  PubMed  Google Scholar 

  10. Rimbaud S, Garnier A, Ventura-Clapier R (2009) Mitochondrial biogenesis in cardiac pathophysiology. Pharmacol Rep 61:131–138. https://doi.org/10.1016/S1734-1140(09)70015-5

    Article  CAS  PubMed  Google Scholar 

  11. Murray AJ, Edwards LM, Clarke K (2007) Mitochondria and heart failure. Curr Opin Clin Nutr Metab Care 10:704–711. https://doi.org/10.1097/MCO.0b013e3282f0ecbe

    Article  CAS  PubMed  Google Scholar 

  12. Mari Kannan M, Darlin Quine S (2012) Ellagic acid protects mitochondria from β-adrenergic agonist induced myocardial damage in rats; evidence from in vivo, in vitro and ultra structural study. Food Res Int 45:1–8. https://doi.org/10.1016/j.foodres.2011.09.018

    Article  CAS  Google Scholar 

  13. Thygesen K, Alpert JS, Jaffe AS et al (2012) Third universal definition of myocardial infarction. Nat Rev Cardiol 9:620–633. https://doi.org/10.1161/CIR.0b013e31826e1058

    Article  PubMed  Google Scholar 

  14. Hare JM (2001) Oxidative stress and apoptosis in heart failure progression. Circ Res 89:198–200

    Article  CAS  PubMed  Google Scholar 

  15. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516. https://doi.org/10.1080/01926230701320337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. El-Missiry MA, Amer MA, Hemieda FA et al (2015) Cardioameliorative effect of punicalagin against streptozotocin-induced apoptosis, redox imbalance, metabolic changes and inflammation. Egypt J Basic Appl Sci 2:247–260. https://doi.org/10.1016/j.ejbas.2015.09.004

    Article  Google Scholar 

  17. Kamatou GPP, Viljoen AM (2010) A review of the application and pharmacological properties of α-bisabolol and α-bisabolol-rich oils. J Am Oil Chem Soc 87:1–7. https://doi.org/10.1007/s11746-009-1483-3

    Article  CAS  Google Scholar 

  18. Buitrago A, Rojas J, Rojas L et al (2015) Essential oil composition and antimicrobial activity of Vismia macrophylla leaves and fruits collected in Tachira-Venezuela. Nat Prod Commun 10:375–377

    PubMed  Google Scholar 

  19. Zargaran A, Borhani-Haghighi A, Faridi P et al (2014) Potential effect and mechanism of action of topical chamomile (Matricaria chammomila L.) oil on migraine headache: a medical hypothesis. Med Hypotheses 83:566–569. https://doi.org/10.1016/j.mehy.2014.08.023

    Article  CAS  PubMed  Google Scholar 

  20. Brehm-Stecher BF, Johnson EA (2003) Sensitization of Staphylococcus aureus and Escherichia coli to antibiotics by the sesquiterpenoids nerolidol, farnesol, bisabolol and apritone. Antimicrob. Agents Chemother 47:3357–3360. https://doi.org/10.1128/AAC.47.10.3357-3360.2003

    Article  CAS  Google Scholar 

  21. Moura Rocha NF, Venancio ET, Moura BA (2010) Gastroprotection of (-) alpha-bisabolol on acute gastric mucosal lesions in mice: the possible involved pharmacological mechanisms. Fundam Clin Pharmacol 24:63–71

    Article  CAS  PubMed  Google Scholar 

  22. Braga PC, Dal Sasso M, Fonti E et al (2009) Antioxidant activity of bisabolol: inhibitory effects on chemiluminescence of human neutrophil bursts and cell free systems. Pharmacology 83:110–115. https://doi.org/10.1159/000186049

    Article  CAS  PubMed  Google Scholar 

  23. Gomes-Carneiro MR, Dias DM, De-Oliveira AC (2005) Evaluation of mutagenic and antimutagenic activities of alpha-bisabolol in the Salmonella⁄microsome assay. Mutat Res 585:105–112

    Article  CAS  PubMed  Google Scholar 

  24. Corpas-Lopez V, Merino-Espinosa G, Lopez-Viota M et al (2016) Topical treatment of Leishmania tropica infection using (-)-α-bisabolol ointment in a Hamster model: effectiveness and safety assessment. J Nat Prod 79:2403–2407. https://doi.org/10.1021/acs.jnatprod.6b00740

    Article  CAS  PubMed  Google Scholar 

  25. Ojha S, Goyal S, Kumari S et al (2012) Pyruvate attenuates cardiac dysfunction and oxidative stress in isoproterenol induced cardiotoxicity. Exp Toxicol Pathol 64:393–399. https://doi.org/10.1016/j.etp.2010.10.004

    Article  CAS  PubMed  Google Scholar 

  26. Ojha S, Bhatia J, Arora S (2011) Cardioprotective effects of Commiphora mukul against isoprenaline-induced cardiotoxicity:a biochemical and histopathological evaluation. J Environ Biol 32:731–738

    CAS  PubMed  Google Scholar 

  27. Ojha S, Goyal S, Sharma C, Arora S, Kumari S, Arya DS (2013) Cardioprotective effect of lycopene against isoproterenol-induced myocardial infarction in rats. Human Exp Toxicol 32:492–503

    Article  CAS  Google Scholar 

  28. Malik S, Goyal S, Ojha SK et al (2011) Seabuckthorn attenuates cardiac dysfunction and oxidative stress in isoproterenol-induced cardiotoxicity in rats. Int J Toxicol 30:671–680. https://doi.org/10.1177/1091581811417898

    Article  CAS  PubMed  Google Scholar 

  29. Ojha S, Azimullah S, Al Taee H, Meeran MFN (2017) Cardioprotective effect of (-)-α-Bisabolol in animal model of myocardial infarction. Planta Med Int 4:83. https://doi.org/10.1055/s-0037-1608133

    Article  Google Scholar 

  30. Fraga CG, Leibovitz BE, Toppel AL (1988) Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: characterization and comparison with homogenates and microsomes. Free Radic Biol Med 4:155–251. https://doi.org/10.1016/0891-5849(88)90023-8

    Article  CAS  PubMed  Google Scholar 

  31. Jiang ZY, Hunt JV, Wolff SP (1992) Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Anal Biochem 202:384–389. https://doi.org/10.1016/0003-2697(92)90122-N

    Article  CAS  PubMed  Google Scholar 

  32. Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21:130–132

    CAS  PubMed  Google Scholar 

  33. Sinha K (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394

    Article  CAS  PubMed  Google Scholar 

  34. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  35. King J (1965) Isocitrate dehydrogenase. In: King JC, Van D (eds) Practical clinical enzymol. Nostrand Co, London, p 363

    Google Scholar 

  36. Mehler H, Kornberg A, Grisolia S et al (1948) The enzymatic mechanism of oxidation-reductions between malate or isocitrate and pyruvate. J Biol Chem 174:961–977

    CAS  PubMed  Google Scholar 

  37. Slater EC, Borner WD Jr (1952) The effect of fluoride on the succinic oxidase system. Biochem J 52:185–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Reed LJ, Mukherjee RB (1969) α-Ketoglutarate dehydrogenase complex from Escherichia coli. In: Lowenstein JM (ed) Methods in enzymology. Academic Press, London, pp 53–61

    Google Scholar 

  39. Kramer KA, Oglesbee D, Hartman SJ (2005) Automated spectrophotometric analysis of mitochondrial respiratory chain complex enzyme activities in cultured skin fibroblasts. Clin Chem 51:2110–2116. https://doi.org/10.1373/clinchem.2005.050146

    Article  CAS  PubMed  Google Scholar 

  40. Pearl W, Cascarano J, Zweifach BW (1963) Microdetermination of cytochrome oxidase in rat tissues by the oxidation on N-phenyl-p-phenylenediamine or ascorbic acid. J Histochem Cytochem 11:102–104

    Article  CAS  Google Scholar 

  41. Williams JR, Coorkey BE (1967) Assay of intermediates of the citric acid cycle and related compounds by flourimetric enzymatic methods. In: Lowenstein JM (ed) Methods in enzymol. Academic Press, New York, pp 488–492

    Google Scholar 

  42. Maloyan A, Sanbe A, Osinska H et al (2005) Mitochondrial dysfunction and apoptosis underlie the pathogenic process in alpha-B-crystallin desmin-related cardiomyopathy. Circulation 112:3451–3461. https://doi.org/10.1161/CIRCULATIONAHA.105.572552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lang RAD (1987). In: Darely-Usmar VM, Reckwood D, Wison MT (eds) Mitochondria, a practical approach. IRL Press Ltd, Washington, pp 17–20

    Google Scholar 

  44. Halliwell B, Gutteridge M, Aruoma OI, The deoxyribose method: a simple “test-tube” assay for determination of rate constants for reactions of hydroxyl radicals. Anal Biochem 255:215–219

  45. Moovendhan M, Seedevi P, Shanmugam A (2016) Exploration of the preventive effect of S. lessoniana liver oil on cardiac markers, hematological patterns and lysosomal hydrolases in isoproterenol-induced myocardial infarction in Wistar rats: a novel report. RSC Adv 6:64147–64154. https://doi.org/10.1039/C6RA11369A

    Article  CAS  Google Scholar 

  46. Senthil Kumaran K, Stanely Mainzen Prince P (2010) Caffeic acid protects rat heart mitochondria against isoproterenol-induced oxidative damage. Cell Stress Chaperones 15:791–806. https://doi.org/10.1007/s12192-010-0187-9

    Article  CAS  Google Scholar 

  47. Zheng XH, Liu CP, Hao ZG et al (2017) Protective effect and mechanistic evaluation of linalool against acute myocardial ischemia and reperfusion injury in rats. RSC Adv 7:34473–34481. https://doi.org/10.1039/C7RA00743D

    Article  CAS  Google Scholar 

  48. Basha RH, Priscilla DH (2011) An in vivo and in vitro study on the protective effects of N-acetylcysteine on mitochondrial dysfunction in isoproterenol treated myocardial infarcted rats. Exp Toxicol Pathol 65:7–14. https://doi.org/10.1016/j.etp.2011.05.002

    Article  CAS  PubMed  Google Scholar 

  49. Plaut WE, Cook M, Aogaichi T (1983) The subcellular location of isozymes of NADP-isocitrate dehydrogenase in tissues from pig, ox and rat. Biochim Biophys Acta 760:300–308. https://doi.org/10.1016/0304-4165(83)90177-0

    Article  CAS  PubMed  Google Scholar 

  50. Yogeeta SK, Raghavendran HR, Gnanapragasam A et al (2006) Ferulic acid with ascorbic acid synergistically extenuates the mitochondrial dysfunction during beta-adrenergic catecholamine induced cardio toxicity in rats. Chem Biol Interact 253:250–259. https://doi.org/10.1016/j.cbi.2006.04.018

    Article  CAS  Google Scholar 

  51. Nagoor Meeran MF, Jagadeesh GS, Selvaraj P (2016) Thymol, a dietary monoterpene phenol abrogates mitochondrial dysfunction in β-adrenergic agonist induced myocardial infarcted rats by inhibiting oxidative stress. Chem Biol Interact 244:159–168. https://doi.org/10.1016/j.cbi.2015.12.006

    Article  CAS  PubMed  Google Scholar 

  52. Ambrosio G, Zweier J, Duilio C (1993) Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow. J Biol Chem 268:18532–18541

    CAS  PubMed  Google Scholar 

  53. Sudheesh NP, Ajith TA, Janardhanan KK (2013) Ganoderma lucidum ameliorate mitochondrial damage in isoproterenol-induced myocardial infarction in rats by enhancing the activities of TCA cycle enzymes and respiratory chain complexes. Int J Cardiol 165:117–125. https://doi.org/10.1016/j.ijcard.2011.07.103

    Article  CAS  PubMed  Google Scholar 

  54. Suchalatha S, Srinivasan P, Shyamala Devi C (2007) Effect of T. chebula on mitochondrial alterations in experimental myocardial injury. Chem Biol Interact 259:145–153. https://doi.org/10.1016/j.cbi.2007.06.034

    Article  CAS  Google Scholar 

  55. Ide T, Tsutsui H, Hayashidani S et al (2001) Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 88:529–535. https://doi.org/10.1161/01.RES.88.5.529

    Article  CAS  PubMed  Google Scholar 

  56. Riba A, Deres L, Sumegi B et al (2017) Cardioprotective effect of resveratrol in a postinfarction heart failure model. Oxid Med Cell Longev 2017:10. https://doi.org/10.1155/2017/6819281

    Article  CAS  Google Scholar 

  57. Starkov AA, Polster BM, Fiskum G (2002) Regulation of hydrogen peroxide production by brain mitochondria by calcium and Bax. J Neurochem 83:220–228. https://doi.org/10.1046/j.1471-4159.2002.01153.x

    Article  CAS  PubMed  Google Scholar 

  58. Abell ED, Doenst T (2011) Mitochondrial adaptations to physiological vs pathological cardiac hypertrophy. Cardiovasc Res 90:234–242. https://doi.org/10.1093/cvr/cvr015

    Article  CAS  Google Scholar 

  59. Wang M, Si JY, Yu Y (2014) Red clover flavonoids protect against oxidative stress-induced cardiotoxicity in vivo and in vitro. RSC Adv 4:54668–54676. https://doi.org/10.1039/C4RA08407A

    Article  CAS  Google Scholar 

  60. Nagoor Meeran MF, Jagadeesh GS, Selvaraj P (2016) Synthetic catecholamine triggers β1-adrenergic receptor activation and stimulates cardiotoxicity via oxidative stress mediated apoptotic cell death in rats: abrogating action of thymol. Chem Biol Interact 251:17–25. https://doi.org/10.1016/j.cbi.2016.03.017

    Article  CAS  Google Scholar 

  61. Radhiga T, Rajamanickam C, Sundaresan A (2012) Effect of ursolic acid treatment on apoptosis and DNA damage in isoproterenol-induced myocardial infarction. Biochimie 94:1135–1142. https://doi.org/10.1016/j.biochi.2012.01.015

    Article  CAS  PubMed  Google Scholar 

  62. Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619. https://doi.org/10.1016/0092-8674(93)90509-O

    Article  CAS  PubMed  Google Scholar 

  63. Sahu BD, Anubolu H, Koneru M (2014) Cardioprotective effect of embelin on isoproterenol-induced myocardial injury in rats: possible involvement of mitochondrial dysfunction and apoptosis. Life Sci 107:59–67. https://doi.org/10.1016/j.lfs.2014.04.035

    Article  CAS  PubMed  Google Scholar 

  64. Joo JH, Ueda E, Bortner CD et al (2015) Farnesol activates the intrinsic pathway of apoptosis and the ATF4-ATF3-CHOP cascade of ER stress in human T-lymphoblastic leukemia Molt4 cells. Biochem Pharmacol 97:256–268. https://doi.org/10.1016/j.bcp.2015.08.086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zhou B, Wu LJ, Tashiro S et al (2006) Silibinin protects rat cardiac myocyte from isoproterenol-induced DNA damage independent on regulation of cell cycle. Biol Pharm Bull 29:1900–1905. https://doi.org/10.1248/bpb.29.1900

    Article  CAS  PubMed  Google Scholar 

  66. Wickens P (2011) Ageing and the free radical theory. Respir Physiol 128:379–391. https://doi.org/10.1016/S0034-5687(01)00313-9

    Article  Google Scholar 

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Acknowledgements

The authors wish to thank United Arab Emirates University for the funding through University Program for Advanced Research (UPAR) (Grant No. 31M195).

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Nagoor Meeran, M.F., Laham, F., Azimullah, S. et al. α-Bisabolol abrogates isoproterenol-induced myocardial infarction by inhibiting mitochondrial dysfunction and intrinsic pathway of apoptosis in rats. Mol Cell Biochem 453, 89–102 (2019). https://doi.org/10.1007/s11010-018-3434-5

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