Potential protective effect of pitavastatin against doxorubicin-induced cardiotoxicity in male rats
Main Article Content
Keywords
Pitavastatin, doxorubicin-induced cardiotoxicity, inflammatory factors, apoptosis markers and oxidative stress
Abstract
Pitavastatin is a synthetic HMG-CoA reductase inhibitor that differs pharmacologically from other statins in a number of ways because of its cyclopropyl moiety. The expression of lipoprotein lipase is higher at low doses than that of other statins, and cholesterol synthesis is inhibited at lower doses than other statins. These effects include notable long-lasting high-density and apolipoprotein A1-raising activity. Compared to other statins, pitavastatin has the highest bioavailability, about (60%) and the majority of this portion is eliminated unchanged in the bile. following oral administration. Doxorubicin-induced cardiotoxicity or heart failure have a number of potential mechanisms. After doxorubicin administration, cardiac muscle cell injuries are primarily caused by the production of free radicals, increased lipid peroxidation and ROS production in cardiac tissues are the first symptoms of dox-induced cardiotoxicity. Reactive oxygen species are promoted by aglycones and their anthracycline iron complexes. Doxorubicin stimulates both the pathways for extrinsic as well as intrinsic apoptosis. These pathways result in the apoptosis of cells in cardiac muscles due to an imbalance between oxidant and anti-oxidant molecules. Doxorubicin decreased cell viability and stimulated an inflammatory response, as evidenced by an increase in levels of the cytokines interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha. 28 male rats were divided into four equal groups at random. The rats were allowed to consume water and food in the control group. The rats in the DMSO group were given 10 ml/kg/day of DMSO orally for two weeks. For two weeks, rats in the doxorubicin group (mediated group) gained 2.5 mg/kg of the medication three times per week. Pitavastatin group: Pitavastatin was given orally over the course of two weeks at a rate of 0.64 mg/kg/day. Tumor necrosis factor, interleukin-1β, malondialdehyde, and caspase-3 levels significantly increased (P<0.05), demonstrating that doxorubicin induced cardiotoxicity, as well as a significant decrease in Bcl-2 levels in cardiac tissues and total antioxidant capacity of treated rats when compared to the DMSO and control groups. Pitavastatin significantly reduces the cardiotoxicity brought on by doxorubicin (P< 0.05), as demonstrated by a drop in inflammatory markers like tumor necrosis factor-α and interleukin-1β. The total antioxidant capacity was significantly higher (P< 0.05) in the pitavastatin group versus the doxorubicin-only group, the oxidative marker MDA was also markedly decreased (P< 0.05) in cardiac tissue. Pitavastatin significantly reduced the cardiotoxicity that the chemotherapy drug doxorubicin caused in rats. This was most likely accomplished byinterference with the apoptotic pathway, inflammation, and oxidative stress. This research sought to determine whether pitavastatin might provide protection against the cardiotoxicity that doxorubicin causes by blocking pathways that promote oxidative stress, inflammation, and apoptosis.
References
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10. Hamidian, G., Zirak, K., Sheikhzadeh, N., Khani Oushani, A., Shabanzadeh, S., & Divband, B. (2018). Intestinal histology and stereology in rainbow trout (Oncorhynchus mykiss) administrated with nanochitosan/zeolite and chitosan/zeolite composites. Aquaculture Research, 49(5), 1803–1815.
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13. Kalyanaraman, B. (2020). Teaching the basics of the mechanism of doxorubicin-induced cardiotoxicity: Have we been barking up the wrong tree? Redox Biology, 29, 101394.
14. Li, J., Wu, Y., Wang, D., Zou, L., Fu, C., Zhang, J., & Leung, G. P.-H. (2019). Oridonin synergistically enhances the anti-tumor efficacy of doxorubicin against aggressive breast cancer via pro-apoptotic and anti-angiogenic effects. Pharmacological Research, 146, 104313.
15. Madeswaran, A. (2017). In Silico, In Vitro And In Vivo Memory Enhancing Activity Of Certain Commercially Available Flavonoids In Scopolamine And Aluminium-Induced Learning Impairment In Mice.
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20. Musumeci, T., Bonaccorso, A., & Puglisi, G. (2019). Epilepsy disease and nose-to-brain delivery of polymeric nanoparticles: an overview. Pharmaceutics, 11(3), 118.
21. Quagliariello, V., De Laurentiis, M., Rea, D., Barbieri, A., Monti, M. G., Carbone, A., Paccone, A., Altucci, L., Conte, M., Canale, M. L., Botti, G., & Maurea, N. (2021). The SGLT-2 inhibitor empagliflozin improves myocardial strain, reduces cardiac fibrosis and pro-inflammatory cytokines in non-diabetic mice treated with doxorubicin. Cardiovascular Diabetology, 20(1), 1–20. https://doi.org/10.1186/S12933-021-01346-Y/FIGURES/8
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23. Renu, K., Abilash, V. G., PB, T. P., & Arunachalam, S. (2018). Molecular mechanism of doxorubicin-induced cardiomyopathy–An update. European Journal of Pharmacology, 818, 241–253.
24. Russo, M., Guida, F., Paparo, L., Trinchese, G., Aitoro, R., Avagliano, C., Fiordelisi, A., Napolitano, F., Mercurio, V., & Sala, V. (2019). The novel butyrate derivative phenylalanine‐butyramide protects from doxorubicin‐induced cardiotoxicity. European Journal of Heart Failure, 21(4), 519–528.
25. Shaker, R. A., Abboud, S. H., Assad, H. C., & Hadi, N. (2018). Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. BMC Pharmacology and Toxicology, 19(1), 1–10.
26. Soltani Hekmat, A., Chenari, A., Alipanah, H., & Javanmardi, K. (2021). Protective effect of alamandine on doxorubicin‑induced nephrotoxicity in rats. BMC Pharmacology and Toxicology, 22(1), 1–11.
27. Tamargo, J., Caballero, R., & Delpón, E. (2022). Cancer chemotherapy-induced sinus bradycardia: a narrative review of a forgotten adverse effect of cardiotoxicity. Drug Safety, 45(2), 101–126.
28. Xian, G., Zhao, J., Qin, C., Zhang, Z., Lin, Y., & Su, Z. (2017). Simvastatin attenuates macrophage-mediated gemcitabine resistance of pancreatic ductal adenocarcinoma by regulating the TGF-β1/Gfi-1 axis. Cancer Letters, 385, 65–74.
29. Zhang, S., You, Z.-Q., Yang, L., Li, L.-L., Wu, Y.-P., Gu, L.-Q., & Xin, Y.-F. (2019). Protective effect of Shenmai injection on doxorubicin-induced cardiotoxicity via regulation of inflammatory mediators. BMC Complementary and Alternative Medicine, 19, 1–10.
30. Alyasiry, E., Janabi, A., & Hadi, N. (2022). Dipyridamole ameliorates doxorubicin-induced cardiotoxicity. Journal of Medicine & Life, 15(9).
31. Aziz, M. M., Abd El Fattah, M. A., Ahmed, K. A., & Sayed, H. M. (2020). Protective effects of olmesartan and l-carnitine on doxorubicin-induced cardiotoxicity in rats. Canadian Journal
of Physiology and Pharmacology, 98(4), 183–193.
32. Babaei, H., Razmaraii, N., Gh, A., Azarmi, Y., Mohammadnejad, D., & Azami, A. (2020). Ultrastructural and echocardiographic assessment of chronic doxorubicin-induced cardiotoxicity in rats. Archives of Razi Institute, 75(1), 55.
33. Bouitbir, J., Sanvee, G. M., Panajatovic, M. V, Singh, F., & Krähenbühl, S. (2020). Mechanisms of statin-associated skeletal muscle-associated symptoms. Pharmacological Research, 154, 104201.
34. Cardinale, D., Iacopo, F., & Cipolla, C. M. (2020). Cardiotoxicity of anthracyclines. Frontiers in Cardiovascular Medicine, 7, 26.
35. Carteri, R. B., Kopczynski, A., Rodolphi, M. S., Strogulski, N. R., Sartor, M., Feldmann, M., De Bastiani, M. A., Duval Wannmacher, C. M., de Franceschi, I. D., & Hansel, G. (2019). Testosterone administration after traumatic brain injury reduces mitochondrial dysfunction and neurodegeneration. Journal of Neurotrauma, 36(14), 2246–2259.
36. Chen, Y.-H., Chen, Y.-C., Lin, C.-C., Hsieh, Y.-P., Hsu, C.-S., & Hsieh, M.-C. (2020). Synergistic anticancer effects of gemcitabine with pitavastatin on pancreatic cancer cell line MIA PaCa-2 in vitro and in vivo. Cancer Management and Research, 12, 4645.
37. Eid, B. G., El‐Shitany, N. A. E., & Neamatallah, T. (2021). Trimetazidine improved adriamycin‐induced cardiomyopathy by downregulating TNF‐α, BAX, and VEGF immunoexpression via an antioxidant mechanism. Environmental Toxicology, 36(6), 1217–1225.
38. Faghihi, N., & Mohammadi, M. T. (2017). Anticonvulsant and antioxidant effects of pitavastatin against pentylenetetrazol-induced kindling in mice. Advanced Pharmaceutical Bulletin, 7(2), 291.
39. Hamidian, G., Zirak, K., Sheikhzadeh, N., Khani Oushani, A., Shabanzadeh, S., & Divband, B. (2018). Intestinal histology and stereology in rainbow trout (Oncorhynchus mykiss) administrated with nanochitosan/zeolite and chitosan/zeolite composites. Aquaculture Research, 49(5), 1803–1815.
40. Hanna, A., & Frangogiannis, N. G. (2020). Inflammatory cytokines and chemokines as therapeutic targets in heart failure. Cardiovascular Drugs and Therapy, 34(6), 849–863.
41. Iqbal, R., Akhtar, M. S., Hassan, M. Q., Jairajpuri, Z., Akhtar, M., & Najmi, A. K. (2019). Pitavastatin ameliorates myocardial damage by preventing inflammation and collagen depositionvia reduced free radical generation in isoproterenol-induced cardiomyopathy. Clinical and Experimental Hypertension, 41(5), 434–443.
42. Kalyanaraman, B. (2020). Teaching the basics of the mechanism of doxorubicin-induced cardiotoxicity: Have we been barking up the wrong tree? Redox Biology, 29, 101394.
43. Li, J., Wu, Y., Wang, D., Zou, L., Fu, C., Zhang, J., & Leung, G. P.-H. (2019). Oridonin synergistically enhances the anti-tumor efficacy of doxorubicin against aggressive breast cancer via pro-apoptotic and anti-angiogenic effects. Pharmacological Research, 146, 104313.
44. Madeswaran, A. (2017). In Silico, In Vitro And In Vivo Memory Enhancing Activity Of Certain Commercially Available Flavonoids In Scopolamine And Aluminium-Induced Learning Impairment In Mice.
45. Malik, S., Sharma, A. K., Bharti, S., Nepal, S., Bhatia, J., Nag, T. C., Narang, R., & Arya, D. S. (2011). In Vivo Cardioprotection by Pitavastatin From Ischemic-reperfusion Injury Through Suppression of IKK/NF-κB and Upregulation of pAkt–e-NOS. Journal of Cardiovascular Pharmacology, 58(2), 199–206.
46. McFarland, A. J., Davey, A. K., McDermott, C. M., Grant, G. D., Lewohl, J., & Anoopkumar-Dukie, S. (2018). Differences in statin associated neuroprotection corresponds with either decreased production of IL-1β or TNF-α in an in vitro model of neuroinflammation-induced neurodegeneration. Toxicology and Applied Pharmacology, 344, 56–73.
47. Moutabian, H., Ghahramani-Asl, R., Mortezazadeh, T., Laripour, R., Narmani, A., Zamani, H., Ataei, G., Bagheri, H., Farhood, B., Sathyapalan, T., & Sahebkar, A. (2022). The cardioprotective effects of nano-curcumin against doxorubicin-induced cardiotoxicity: A systematic review. BioFactors, 48(3), 597–610. https://doi.org/10.1002/BIOF.1823
48. Mudd Jr, T. W., Khalid, M., & Guddati, A. K. (2021). Cardiotoxicity of chemotherapy and targeted agents. American Journal of Cancer Research, 11(4), 1132.
49. Musumeci, T., Bonaccorso, A., & Puglisi, G. (2019). Epilepsy disease and nose-to-brain delivery of polymeric nanoparticles: an overview. Pharmaceutics, 11(3), 118.
50. Quagliariello, V., De Laurentiis, M., Rea, D., Barbieri, A., Monti, M. G., Carbone, A., Paccone, A., Altucci, L., Conte, M., Canale, M. L., Botti, G., & Maurea, N. (2021). The SGLT-2 inhibitor empagliflozin improves myocardial strain, reduces cardiac fibrosis and pro-inflammatory cytokines in non-diabetic mice treated with
doxorubicin. Cardiovascular Diabetology, 20(1), 1–20. https://doi.org/10.1186/S12933-021-01346-Y/FIGURES/8
51. Rawat, P. S., Jaiswal, A., Khurana, A., Bhatti, J. S., & Navik, U. (2021). Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomedicine and Pharmacotherapy, 139, 111708. https://doi.org/10.1016/j.biopha.2021.111708
52. Renu, K., Abilash, V. G., PB, T. P., & Arunachalam, S. (2018). Molecular mechanism of doxorubicin-induced cardiomyopathy–An update. European Journal of Pharmacology, 818, 241–253.
53. Russo, M., Guida, F., Paparo, L., Trinchese, G., Aitoro, R., Avagliano, C., Fiordelisi, A., Napolitano, F., Mercurio, V., & Sala, V. (2019). The novel butyrate derivative phenylalanine‐butyramide protects from doxorubicin‐induced cardiotoxicity. European Journal of Heart Failure, 21(4), 519–528.
54. Shaker, R. A., Abboud, S. H., Assad, H. C., & Hadi, N. (2018). Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. BMC Pharmacology and Toxicology, 19(1), 1–10.
55. Soltani Hekmat, A., Chenari, A., Alipanah, H., & Javanmardi, K. (2021). Protective effect of alamandine on doxorubicin‑induced nephrotoxicity in rats. BMC Pharmacology and Toxicology, 22(1), 1–11.
56. Tamargo, J., Caballero, R., & Delpón, E. (2022). Cancer chemotherapy-induced sinus bradycardia: a narrative review of a forgotten adverse effect of cardiotoxicity. Drug Safety, 45(2), 101–126.
57. Xian, G., Zhao, J., Qin, C., Zhang, Z., Lin, Y., & Su, Z. (2017). Simvastatin attenuates macrophage-mediated gemcitabine resistance of pancreatic ductal adenocarcinoma by regulating the TGF-β1/Gfi-1 axis. Cancer Letters, 385, 65–74.
58. Zhang, S., You, Z.-Q., Yang, L., Li, L.-L., Wu, Y.-P., Gu, L.-Q., & Xin, Y.-F. (2019). Protective effect of Shenmai injection on doxorubicin-induced cardiotoxicity via regulation of inflammatory mediators. BMC Complementary and Alternative Medicine, 19, 1–10.
2. Aziz, M. M., Abd El Fattah, M. A., Ahmed, K. A., & Sfayed, H. M. (2020). Protective effects of olmesartan and l-carnitine on doxorubicin-induced cardiotoxicity in rats. Canadian Journal of Physiology and Pharmacology, 98(4), 183–193.
3. Babaei, H., Razmaraii, N., Gh, A., Azarmi, Y., Mohammadnejad, D., & Azami, A. (2020).Ultrastructural and echocardiographic assessment of chronic doxorubicin-induced cardiotoxicity in rats. Archives of Razi Institute, 75(1), 55.
4. Bouitbir, J., Sanvee, G. M., Panajatovic, M. V, Singh, F., & Krähenbühl, S. (2020). Mechanisms of statin-associated skeletal muscle-associated symptoms. Pharmacological Research, 154, 104201.
5. Cardinale, D., Iacopo, F., & Cipolla, C. M. (2020). Cardiotoxicity of anthracyclines. Frontiers in Cardiovascular Medicine, 7, 26.
6. Carteri, R. B., Kopczynski, A., Rodolphi, M. S., Strogulski, N. R., Sartor, M., Feldmann, M., De Bastiani, M. A., Duval Wannmacher, C. M., de Franceschi, I. D., & Hansel, G. (2019). Testosterone administration after traumatic brain injury reduces mitochondrial dysfunction and neurodegeneration. Journal of Neurotrauma, 36(14), 2246–2259.
7. Chen, Y.-H., Chen, Y.-C., Lin, C.-C., Hsieh, Y.-P., Hsu, C.-S., & Hsieh, M.-C. (2020). Synergistic anticancer effects of gemcitabine with pitavastatin on pancreatic cancer cell line MIA PaCa-2 in vitro and in vivo. Cancer Management and Research, 12, 4645.
8. Eid, B. G., El‐Shitany, N. A. E., & Neamatallah, T. (2021). Trimetazidine improved adriamycin‐induced cardiomyopathy by downregulating TNF‐α, BAX, and VEGF immunoexpression via an antioxidant mechanism. Environmental Toxicology, 36(6), 1217–1225.
9. Faghihi, N., & Mohammadi, M. T. (2017). Anticonvulsant and antioxidant effects of pitavastatin against pentylenetetrazol-induced kindling in mice. Advanced Pharmaceutical Bulletin, 7(2), 291.
10. Hamidian, G., Zirak, K., Sheikhzadeh, N., Khani Oushani, A., Shabanzadeh, S., & Divband, B. (2018). Intestinal histology and stereology in rainbow trout (Oncorhynchus mykiss) administrated with nanochitosan/zeolite and chitosan/zeolite composites. Aquaculture Research, 49(5), 1803–1815.
11. Hanna, A., & Frangogiannis, N. G. (2020). Inflammatory cytokines and chemokines as therapeutic targets in heart failure. Cardiovascular Drugs and Therapy, 34(6), 849–863.
12. Iqbal, R., Akhtar, M. S., Hassan, M. Q., Jairajpuri, Z., Akhtar, M., & Najmi, A. K. (2019). Pitavastatin ameliorates myocardial damage by preventing inflammation and collagen deposition via reduced free radical generation in isoproterenol-induced cardiomyopathy. Clinical and Experimental Hypertension, 41(5), 434–443.
13. Kalyanaraman, B. (2020). Teaching the basics of the mechanism of doxorubicin-induced cardiotoxicity: Have we been barking up the wrong tree? Redox Biology, 29, 101394.
14. Li, J., Wu, Y., Wang, D., Zou, L., Fu, C., Zhang, J., & Leung, G. P.-H. (2019). Oridonin synergistically enhances the anti-tumor efficacy of doxorubicin against aggressive breast cancer via pro-apoptotic and anti-angiogenic effects. Pharmacological Research, 146, 104313.
15. Madeswaran, A. (2017). In Silico, In Vitro And In Vivo Memory Enhancing Activity Of Certain Commercially Available Flavonoids In Scopolamine And Aluminium-Induced Learning Impairment In Mice.
16. Malik, S., Sharma, A. K., Bharti, S., Nepal, S., Bhatia, J., Nag, T. C., Narang, R., & Arya, D. S. (2011). In Vivo Cardioprotection by Pitavastatin From Ischemic-reperfusion Injury Through Suppression of IKK/NF-κB and Upregulation of pAkt–e-NOS. Journal of Cardiovascular Pharmacology, 58(2), 199–206.
17. McFarland, A. J., Davey, A. K., McDermott, C. M., Grant, G. D., Lewohl, J., & Anoopkumar-Dukie, S. (2018). Differences in statin associated neuroprotection corresponds with either decreased production of IL-1β or TNF-α in an in vitro model of neuroinflammation-induced neurodegeneration. Toxicology and Applied Pharmacology, 344, 56–73.
18. Moutabian, H., Ghahramani-Asl, R., Mortezazadeh, T., Laripour, R., Narmani, A., Zamani, H., Ataei, G., Bagheri, H., Farhood, B., Sathyapalan, T., & Sahebkar, A. (2022). The cardioprotective effects of nano-curcumin against doxorubicin-induced cardiotoxicity: A systematic review. BioFactors, 48(3), 597–610. https://doi.org/10.1002/BIOF.1823
19. Mudd Jr, T. W., Khalid, M., & Guddati, A. K. (2021). Cardiotoxicity of chemotherapy and targeted agents. American Journal of Cancer Research, 11(4), 1132.
20. Musumeci, T., Bonaccorso, A., & Puglisi, G. (2019). Epilepsy disease and nose-to-brain delivery of polymeric nanoparticles: an overview. Pharmaceutics, 11(3), 118.
21. Quagliariello, V., De Laurentiis, M., Rea, D., Barbieri, A., Monti, M. G., Carbone, A., Paccone, A., Altucci, L., Conte, M., Canale, M. L., Botti, G., & Maurea, N. (2021). The SGLT-2 inhibitor empagliflozin improves myocardial strain, reduces cardiac fibrosis and pro-inflammatory cytokines in non-diabetic mice treated with doxorubicin. Cardiovascular Diabetology, 20(1), 1–20. https://doi.org/10.1186/S12933-021-01346-Y/FIGURES/8
22. Rawat, P. S., Jaiswal, A., Khurana, A., Bhatti, J. S., & Navik, U. (2021). Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomedicine and Pharmacotherapy, 139, 111708. https://doi.org/10.1016/j.biopha.2021.111708
23. Renu, K., Abilash, V. G., PB, T. P., & Arunachalam, S. (2018). Molecular mechanism of doxorubicin-induced cardiomyopathy–An update. European Journal of Pharmacology, 818, 241–253.
24. Russo, M., Guida, F., Paparo, L., Trinchese, G., Aitoro, R., Avagliano, C., Fiordelisi, A., Napolitano, F., Mercurio, V., & Sala, V. (2019). The novel butyrate derivative phenylalanine‐butyramide protects from doxorubicin‐induced cardiotoxicity. European Journal of Heart Failure, 21(4), 519–528.
25. Shaker, R. A., Abboud, S. H., Assad, H. C., & Hadi, N. (2018). Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. BMC Pharmacology and Toxicology, 19(1), 1–10.
26. Soltani Hekmat, A., Chenari, A., Alipanah, H., & Javanmardi, K. (2021). Protective effect of alamandine on doxorubicin‑induced nephrotoxicity in rats. BMC Pharmacology and Toxicology, 22(1), 1–11.
27. Tamargo, J., Caballero, R., & Delpón, E. (2022). Cancer chemotherapy-induced sinus bradycardia: a narrative review of a forgotten adverse effect of cardiotoxicity. Drug Safety, 45(2), 101–126.
28. Xian, G., Zhao, J., Qin, C., Zhang, Z., Lin, Y., & Su, Z. (2017). Simvastatin attenuates macrophage-mediated gemcitabine resistance of pancreatic ductal adenocarcinoma by regulating the TGF-β1/Gfi-1 axis. Cancer Letters, 385, 65–74.
29. Zhang, S., You, Z.-Q., Yang, L., Li, L.-L., Wu, Y.-P., Gu, L.-Q., & Xin, Y.-F. (2019). Protective effect of Shenmai injection on doxorubicin-induced cardiotoxicity via regulation of inflammatory mediators. BMC Complementary and Alternative Medicine, 19, 1–10.
30. Alyasiry, E., Janabi, A., & Hadi, N. (2022). Dipyridamole ameliorates doxorubicin-induced cardiotoxicity. Journal of Medicine & Life, 15(9).
31. Aziz, M. M., Abd El Fattah, M. A., Ahmed, K. A., & Sayed, H. M. (2020). Protective effects of olmesartan and l-carnitine on doxorubicin-induced cardiotoxicity in rats. Canadian Journal
of Physiology and Pharmacology, 98(4), 183–193.
32. Babaei, H., Razmaraii, N., Gh, A., Azarmi, Y., Mohammadnejad, D., & Azami, A. (2020). Ultrastructural and echocardiographic assessment of chronic doxorubicin-induced cardiotoxicity in rats. Archives of Razi Institute, 75(1), 55.
33. Bouitbir, J., Sanvee, G. M., Panajatovic, M. V, Singh, F., & Krähenbühl, S. (2020). Mechanisms of statin-associated skeletal muscle-associated symptoms. Pharmacological Research, 154, 104201.
34. Cardinale, D., Iacopo, F., & Cipolla, C. M. (2020). Cardiotoxicity of anthracyclines. Frontiers in Cardiovascular Medicine, 7, 26.
35. Carteri, R. B., Kopczynski, A., Rodolphi, M. S., Strogulski, N. R., Sartor, M., Feldmann, M., De Bastiani, M. A., Duval Wannmacher, C. M., de Franceschi, I. D., & Hansel, G. (2019). Testosterone administration after traumatic brain injury reduces mitochondrial dysfunction and neurodegeneration. Journal of Neurotrauma, 36(14), 2246–2259.
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Apr 25, 2023
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Mohammed K. Al-Chlaihawi, & Ali M. Janabi. (2023). Potential protective effect of pitavastatin against doxorubicin-induced cardiotoxicity in male rats. Journal of Population Therapeutics and Clinical Pharmacology, 30(8), 338–348. https://doi.org/10.47750/jptcp.2023.30.08.037
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