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Adenosine Triphosphate Exerts Cardioprotective Effect on High-Dose Atorvastatin-Induced Heart Damage in Rats

Year 2022, Volume: 15 Issue: 2, 533 - 543, 31.08.2022
https://doi.org/10.18185/erzifbed.1033778

Abstract

Atorvastatin is a statin derivated hypolipidemic drug used in the treatment of hyperlipidemia. High-dose atorvastatin has been shown to significantly reduce adenosine triphosphate (ATP) levels in the heart tissue. Reduction of ATP by atorvastatin causes increased production of reactive oxygen species (ROS), decreased antioxidants, subsequent cell membrane and mitochondrial damage. The present study aimed to biochemically investigate the protective effect of ATP against possible cardiac damage caused by high dose atorvastatin in rats. Male Wistar rats were divided into atorvastatin (ATR), atorvastatin+ATP (AAT) and healthy control (HG) groups. ATP at a 25 mg/kg dose was injected intraperitoneally (ip) to the AAT (n-6) group. 0.9% NaCl as solvent was applied to the ATR (n-6) and HG (n-6) groups by the same route. Afterward, atorvastatin was administered orally at a dose of 20 mg/kg to the AAT and ATR groups. This procedure was repeated once daily for four weeks. At the end of this period, blood samples were taken into tubes to analyze troponin-I (TP-I) by cardiac puncture before animals were sacrificed with high-dose anesthesia. In addition, heart tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), total oxidant (TOS) and total antioxidant (TAS) levels were measured. Biochemical test results showed that in the heart tissues of the ATR group, the oxidative parameters MDA and TOS significantly increased, while the antioxidant parameters tGSH and TAS significantly decreased compared to AAT and HG. Atorvastatin alone administration significantly increased blood TP-I levels, a marker of cardiac tissue damage. However, ATP administration to AAT group animals brought oxidative parameter levels closer to HG, despite high-dose atorvastatin treatment. In addition, the significant decrease in antioxidant levels was prevented by ATP application. High doses of atorvastatin can cause heart damage. ATP treatment was able to prevent atorvastatin-induced oxidative heart damage.

References

  • Abdoli, N., Heidari, R., Azarmi, Y., and Eghbal, M. A. (2013). Mechanisms of the statins cytotoxicity in freshly isolated rat hepatocytes. Journal of biochemical and molecular toxicology, 27(6), 287-294.
  • Aldemir, M. N., Simsek, M., Kara, A. V., Ozcicek, F., Mammadov, R., Yazıcı, G. N., and Suleyman, H. (2020). The effect of adenosine triphosphate on sunitinib-induced cardiac injury in rats. Hum Exp Toxicol, 39(8), 1046-1053.
  • Andalib, S., Shayanfar, A., Khorrami, A., Maleki-Dijazi, N., and Garjani, A. (2014). Atorvastatin reduces the myocardial content of coenzyme Q10 in isoproterenol-induced heart failure in rats. Drug research, 64(05), 246-250.
  • Beltowski, J., Wojcicka, G., and Jamroz-Wisniewska, A. (2009). Adverse effects of statins-mechanisms and consequences. Current drug safety, 4(3), 209-228.
  • Berwanger, O., Santucci, E. V., de Andrade Jesuíno, I., Damiani, L. P., Barbosa, L. M., Santos, R. H. N., and Orto, F. T. C. D. (2018). Effect of loading dose of atorvastatin prior to planned percutaneous coronary intervention on major adverse cardiovascular events in acute coronary syndrome: the SECURE-PCI randomized clinical trial. Jama, 319(13), 1331-1340.
  • Bleske, B. E., Willis, R. A., Anthony, M., Casselberry, N., Datwani, M., Uhley, V. E., and Shea, M. J. (2001). The effect of pravastatin and atorvastatin on coenzyme Q10. American Heart Journal, 142(2), 13A-18A.
  • Bulanova, E., and Bulfone-Paus, S. (2010). P2 receptor-mediated signaling in mast cell biology. Purinergic signalling, 6(1), 3-17.
  • Catapano, A., Graham, I., De Backer, G., Wiklund, O., Chapman, M., and Drexel, H. (2017). Dislipidemilerin tedavisine ilişkin 2016 ESC/EAS Kılavuzu. Türk Kardiyol Dern Arş.
  • Chen, Y.-R., and Zweier, J. L. (2014). Cardiac mitochondria and reactive oxygen species generation. Circulation research, 114(3), 524-537.
  • Cheng, C., Liu, X. B., Bi, S. J., Lu, Q. H., and Zhang, J. (2020). Inhibition of Rho‑kinase is involved in the therapeutic effects of atorvastatin in heart ischemia/reperfusion. Experimental and Therapeutic Medicine, 20(4), 3147-3153.
  • CK, M. (2000). Van Holde KE. Ahern KG. Biochemistry. Third edition, Longman. SanFrancisco, 525-556.
  • Cosgun, M., Coskun, R., and Celik, A. (2021). Effects of Adenosine Triphosphate on Vandetanib-Induced Heart Damage in Rats. INTERNATIONAL JOURNAL OF PHARMACOLOGY, 17(3), 122-129.
  • Coskun, R., Inan, A., Suleyman, Z., Cimen, F. K., and Cankaya, M. (2019). THE PREVENTIVE EFFECTS OF RUTIN ON IMMOBILIZATION STRESS-INDUCED CARDIAC DAMAGE IN RATS. Acta Poloniae Pharmaceutica-Drug Research, 76(6), 1079-1087.
  • Dagli-Hernandez, C., Zhou, Y., Lauschke, V. M., Genvigir, F. D. V., Hirata, T. D. C., Hirata, M. H., and Hirata, R. D. C. (2021). Pharmacogenomics of statins: lipid response and other outcomes in Brazilian cohorts. Pharmacological Reports, 1-20.
  • Erdem, K. T. O., Bedir, Z., Ates, I., Kuyrukluyildiz, U., Coban, T. A., Yazici, G. N., and Suleyman, H. (2021). The effect of adenosine triphosphate on propofol-induced myopathy in rats: a biochemical and histopathological evaluation. The Korean journal of physiology & pharmacology: official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 25(1), 69-77.
  • Erel, O. (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clinical biochemistry, 37(2), 112-119.
  • Erel, O. (2005). A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry, 38(12), 1103-1111.
  • Faki, H. E., Tras, B., and Uney, K. (2020). Alpha lipoic acid and vitamin E improve atorvastatin-induced mitochondrial dysfunctions in rats. Mitochondrion, 52, 83-88.
  • Folkers, K., Langsjoen, P., Willis, R., Richardson, P., Xia, L.-J., Ye, C.-Q., and Tamagawa, H. (1990). Lovastatin decreases coenzyme Q levels in humans. Proceedings of the National Academy of Sciences, 87(22), 8931-8934.
  • Ghonimi, N. A., Elsharkawi, K. A., Khyal, D. S., and Abdelghani, A. A. (2021). Serum malondialdehyde as a lipid peroxidation marker in multiple sclerosis patients and its relation to disease characteristics. Multiple Sclerosis and Related Disorders, 51, 102941.
  • Goodarzi, Z., Karami, E., Yousefi, S., Dehdashti, A., Bandegi, A. R., and Ghanbari, A. (2020). Hepatoprotective effect of atorvastatin on Cadmium chloride induced hepatotoxicity in rats. Life sciences, 254, 117770.
  • Herron, C., Brueckner, C., Chism, J., Kemp, D., Prescott, J., Smith, G., and Polli, J. (2015). Toxicokinetics and toxicity of atorvastatin in dogs. Toxicology and applied pharmacology, 289(1), 117-123.
  • Icel, E., Suleyman, H., Yazici, G. N., Bakan, N., and Sunar, M. (2020). Effects of adenosine triphosphate on methanol-induced experimental optic nerve damage in rats: biochemical and histopathological evaluation. Cutaneous and Ocular Toxicology, 39(3), 244-248.
  • Kisaoglu, A., Borekci, B., Yapca, O. E., Bilen, H.,and Suleyman, H. (2013). Tissue damage and oxidant/antioxidant balance. The Eurasian journal of medicine, 45(1), 47.
  • Li, L. Z., Zhao, Z. M., Zhang, L., He, J., Zhang, T. F., Guo, J. B., and Peng, S. Q. (2019). Atorvastatin induces mitochondrial dysfunction and cell apoptosis in HepG2 cells via inhibition of the Nrf2 pathway. Journal of Applied Toxicology, 39(10), 1394-1404.
  • Nemati, M., Srai, M., and Rudrangi, R. (2021). Statin-Induced Autoimmune Myopathy. Cureus, 13(2).
  • Ohkawa, H., Ohishi, N., and Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry, 95(2), 351-358.
  • Okuyama, H., Langsjoen, P. H., Hamazaki, T., Ogushi, Y., Hama, R., Kobayashi, T., and Uchino, H. (2015). Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms. Expert review of clinical pharmacology, 8(2), 189-199.
  • Owen, J. B., and Butterfield, D. A. (2010). Measurement of oxidized/reduced glutathione ratio Protein misfolding and cellular stress in disease and aging (pp. 269-277): Springer.
  • Sedlak, J., and Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry, 25, 192-205.
  • Silver, M. A., Langsjoen, P. H., Szabo, S., Patil, H., and Zelinger, A. (2003). Statin cardiomyopathy? A potential role for Co-Enzyme Q_ {10} therapy for statin-induced changes in diastolic LV performance: Description of a clinical protocol. Biofactors, 18(1-4), 125-127.
  • Silver, M. A., Langsjoen, P. H., Szabo, S., Patil, H., and Zelinger, A. (2004). Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction. The American journal of cardiology, 94(10), 1306-1310.
  • Thygesen, K., Alpert, J. S., Jaffe, A. S., Chaitman, B. R., Bax, J. J., Morrow, D. A., and Van de Werf, F. (2019). Fourth universal definition of myocardial infarction (2018). European heart journal, 40(3), 237-269.
  • Váli, L., Hahn, O., Kupcsulik, P., Drahos, Á., Sárváry, E., Szentmihályi, K., and Blázovics, A. (2008). Oxidative stress with altered element content and decreased ATP level of erythrocytes in hepatocellular carcinoma and colorectal liver metastases. European journal of gastroenterology & hepatology, 20(5), 393-398.
Year 2022, Volume: 15 Issue: 2, 533 - 543, 31.08.2022
https://doi.org/10.18185/erzifbed.1033778

Abstract

References

  • Abdoli, N., Heidari, R., Azarmi, Y., and Eghbal, M. A. (2013). Mechanisms of the statins cytotoxicity in freshly isolated rat hepatocytes. Journal of biochemical and molecular toxicology, 27(6), 287-294.
  • Aldemir, M. N., Simsek, M., Kara, A. V., Ozcicek, F., Mammadov, R., Yazıcı, G. N., and Suleyman, H. (2020). The effect of adenosine triphosphate on sunitinib-induced cardiac injury in rats. Hum Exp Toxicol, 39(8), 1046-1053.
  • Andalib, S., Shayanfar, A., Khorrami, A., Maleki-Dijazi, N., and Garjani, A. (2014). Atorvastatin reduces the myocardial content of coenzyme Q10 in isoproterenol-induced heart failure in rats. Drug research, 64(05), 246-250.
  • Beltowski, J., Wojcicka, G., and Jamroz-Wisniewska, A. (2009). Adverse effects of statins-mechanisms and consequences. Current drug safety, 4(3), 209-228.
  • Berwanger, O., Santucci, E. V., de Andrade Jesuíno, I., Damiani, L. P., Barbosa, L. M., Santos, R. H. N., and Orto, F. T. C. D. (2018). Effect of loading dose of atorvastatin prior to planned percutaneous coronary intervention on major adverse cardiovascular events in acute coronary syndrome: the SECURE-PCI randomized clinical trial. Jama, 319(13), 1331-1340.
  • Bleske, B. E., Willis, R. A., Anthony, M., Casselberry, N., Datwani, M., Uhley, V. E., and Shea, M. J. (2001). The effect of pravastatin and atorvastatin on coenzyme Q10. American Heart Journal, 142(2), 13A-18A.
  • Bulanova, E., and Bulfone-Paus, S. (2010). P2 receptor-mediated signaling in mast cell biology. Purinergic signalling, 6(1), 3-17.
  • Catapano, A., Graham, I., De Backer, G., Wiklund, O., Chapman, M., and Drexel, H. (2017). Dislipidemilerin tedavisine ilişkin 2016 ESC/EAS Kılavuzu. Türk Kardiyol Dern Arş.
  • Chen, Y.-R., and Zweier, J. L. (2014). Cardiac mitochondria and reactive oxygen species generation. Circulation research, 114(3), 524-537.
  • Cheng, C., Liu, X. B., Bi, S. J., Lu, Q. H., and Zhang, J. (2020). Inhibition of Rho‑kinase is involved in the therapeutic effects of atorvastatin in heart ischemia/reperfusion. Experimental and Therapeutic Medicine, 20(4), 3147-3153.
  • CK, M. (2000). Van Holde KE. Ahern KG. Biochemistry. Third edition, Longman. SanFrancisco, 525-556.
  • Cosgun, M., Coskun, R., and Celik, A. (2021). Effects of Adenosine Triphosphate on Vandetanib-Induced Heart Damage in Rats. INTERNATIONAL JOURNAL OF PHARMACOLOGY, 17(3), 122-129.
  • Coskun, R., Inan, A., Suleyman, Z., Cimen, F. K., and Cankaya, M. (2019). THE PREVENTIVE EFFECTS OF RUTIN ON IMMOBILIZATION STRESS-INDUCED CARDIAC DAMAGE IN RATS. Acta Poloniae Pharmaceutica-Drug Research, 76(6), 1079-1087.
  • Dagli-Hernandez, C., Zhou, Y., Lauschke, V. M., Genvigir, F. D. V., Hirata, T. D. C., Hirata, M. H., and Hirata, R. D. C. (2021). Pharmacogenomics of statins: lipid response and other outcomes in Brazilian cohorts. Pharmacological Reports, 1-20.
  • Erdem, K. T. O., Bedir, Z., Ates, I., Kuyrukluyildiz, U., Coban, T. A., Yazici, G. N., and Suleyman, H. (2021). The effect of adenosine triphosphate on propofol-induced myopathy in rats: a biochemical and histopathological evaluation. The Korean journal of physiology & pharmacology: official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 25(1), 69-77.
  • Erel, O. (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clinical biochemistry, 37(2), 112-119.
  • Erel, O. (2005). A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry, 38(12), 1103-1111.
  • Faki, H. E., Tras, B., and Uney, K. (2020). Alpha lipoic acid and vitamin E improve atorvastatin-induced mitochondrial dysfunctions in rats. Mitochondrion, 52, 83-88.
  • Folkers, K., Langsjoen, P., Willis, R., Richardson, P., Xia, L.-J., Ye, C.-Q., and Tamagawa, H. (1990). Lovastatin decreases coenzyme Q levels in humans. Proceedings of the National Academy of Sciences, 87(22), 8931-8934.
  • Ghonimi, N. A., Elsharkawi, K. A., Khyal, D. S., and Abdelghani, A. A. (2021). Serum malondialdehyde as a lipid peroxidation marker in multiple sclerosis patients and its relation to disease characteristics. Multiple Sclerosis and Related Disorders, 51, 102941.
  • Goodarzi, Z., Karami, E., Yousefi, S., Dehdashti, A., Bandegi, A. R., and Ghanbari, A. (2020). Hepatoprotective effect of atorvastatin on Cadmium chloride induced hepatotoxicity in rats. Life sciences, 254, 117770.
  • Herron, C., Brueckner, C., Chism, J., Kemp, D., Prescott, J., Smith, G., and Polli, J. (2015). Toxicokinetics and toxicity of atorvastatin in dogs. Toxicology and applied pharmacology, 289(1), 117-123.
  • Icel, E., Suleyman, H., Yazici, G. N., Bakan, N., and Sunar, M. (2020). Effects of adenosine triphosphate on methanol-induced experimental optic nerve damage in rats: biochemical and histopathological evaluation. Cutaneous and Ocular Toxicology, 39(3), 244-248.
  • Kisaoglu, A., Borekci, B., Yapca, O. E., Bilen, H.,and Suleyman, H. (2013). Tissue damage and oxidant/antioxidant balance. The Eurasian journal of medicine, 45(1), 47.
  • Li, L. Z., Zhao, Z. M., Zhang, L., He, J., Zhang, T. F., Guo, J. B., and Peng, S. Q. (2019). Atorvastatin induces mitochondrial dysfunction and cell apoptosis in HepG2 cells via inhibition of the Nrf2 pathway. Journal of Applied Toxicology, 39(10), 1394-1404.
  • Nemati, M., Srai, M., and Rudrangi, R. (2021). Statin-Induced Autoimmune Myopathy. Cureus, 13(2).
  • Ohkawa, H., Ohishi, N., and Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry, 95(2), 351-358.
  • Okuyama, H., Langsjoen, P. H., Hamazaki, T., Ogushi, Y., Hama, R., Kobayashi, T., and Uchino, H. (2015). Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms. Expert review of clinical pharmacology, 8(2), 189-199.
  • Owen, J. B., and Butterfield, D. A. (2010). Measurement of oxidized/reduced glutathione ratio Protein misfolding and cellular stress in disease and aging (pp. 269-277): Springer.
  • Sedlak, J., and Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry, 25, 192-205.
  • Silver, M. A., Langsjoen, P. H., Szabo, S., Patil, H., and Zelinger, A. (2003). Statin cardiomyopathy? A potential role for Co-Enzyme Q_ {10} therapy for statin-induced changes in diastolic LV performance: Description of a clinical protocol. Biofactors, 18(1-4), 125-127.
  • Silver, M. A., Langsjoen, P. H., Szabo, S., Patil, H., and Zelinger, A. (2004). Effect of atorvastatin on left ventricular diastolic function and ability of coenzyme Q10 to reverse that dysfunction. The American journal of cardiology, 94(10), 1306-1310.
  • Thygesen, K., Alpert, J. S., Jaffe, A. S., Chaitman, B. R., Bax, J. J., Morrow, D. A., and Van de Werf, F. (2019). Fourth universal definition of myocardial infarction (2018). European heart journal, 40(3), 237-269.
  • Váli, L., Hahn, O., Kupcsulik, P., Drahos, Á., Sárváry, E., Szentmihályi, K., and Blázovics, A. (2008). Oxidative stress with altered element content and decreased ATP level of erythrocytes in hepatocellular carcinoma and colorectal liver metastases. European journal of gastroenterology & hepatology, 20(5), 393-398.
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Details

Primary Language English
Subjects Engineering
Journal Section Makaleler
Authors

Resit Coskun 0000-0002-0312-2009

Early Pub Date August 29, 2022
Publication Date August 31, 2022
Published in Issue Year 2022 Volume: 15 Issue: 2

Cite

APA Coskun, R. (2022). Adenosine Triphosphate Exerts Cardioprotective Effect on High-Dose Atorvastatin-Induced Heart Damage in Rats. Erzincan University Journal of Science and Technology, 15(2), 533-543. https://doi.org/10.18185/erzifbed.1033778