Author(s):
Diksha Verma, Dinesh Kumar, Ramica Sharma
Email(s):
ramica.17740@rayatbahrauniversity.edu.in
DOI:
10.52711/0974-360X.2025.00447 
Address:
Diksha Verma1, Dinesh Kumar2, Ramica Sharma1*
1University School of Pharmaceutical Sciences, Rayat Bahra University, Mohali, Punjab, India.
2Hans Foundation, Himachal Pradesh, India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 7,
Year - 2025
ABSTRACT:
Anthracyclines are among the most potent chemotherapeutic agent. Quinine- containing anthracycline antibiotic doxorubicin among the most potent chemotherapeutic agent. DOX causes an imbalance in the level of free oxygen radicals and antioxidants. The present study is designed to investigate the cardio and nephro protective effect of atorvastatin and fenofibrate in doxorubicin imduced cardiotoxicity and nephrotoxicityin rats. Atorvastatin is a member of the statin class of HMG-CoA reductase inhibitors and play a revolutionized role in the treatment of hypercholesterolemia. However, Fibrates are also used in therapy in many forms of hypercholesterolemia, usually in combination with statins. The result showed that Doxorubicin causes toxicity in heart and kidney along with liver. When treated with atorvastatin and fenofibrate then the level of CK-MB and LDH is decreased in heart and in kidney the level of Serum Cretinine and BUN is decreased. Atorvastatin and Fenofibrate significantly inhibit DOX-induced nephro-cardio oxidative stress as seen in the reduced level of Thio-barbituric acid Reactive substances (TBAR),SOD and GSH. In addition, there was significant changes confirmed by Histopathological studies. Hence, the present study confirms that atorvastatin and fenofibrate improve the cardiotoxic and nephrotoxic effect induced by doxorubicin through the regulation of oxidative stress response by HMG-CoA and PPAR-a pathway. The overall conclusion for the experimental study is Atorvastatin and Fenofibrate shows the protective role against Doxorubicin induced cardotoxicity and nephrotoxicity.
Cite this article:
Diksha Verma, Dinesh Kumar, Ramica Sharma. Synergestic effect of Atorvastatin and Fenofibrate in Doxorubicin Induced Cardio-Nephrotoxicity. Research Journal of Pharmacy and Technology. 2025;18(7):3110-6. doi: 10.52711/0974-360X.2025.00447
Cite(Electronic):
Diksha Verma, Dinesh Kumar, Ramica Sharma. Synergestic effect of Atorvastatin and Fenofibrate in Doxorubicin Induced Cardio-Nephrotoxicity. Research Journal of Pharmacy and Technology. 2025;18(7):3110-6. doi: 10.52711/0974-360X.2025.00447 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2025-18-7-27
REFERENCES:
1. DeSantis CE, Siegel RL, Sauer AG, Miller KD, Fedewa SA, Alcaraz KI, Jemal A. Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities. CA: A Cancer Journal for Clinicians. 2016; Jul; 66(4): 290-308. https://doi.org/10.3322/caac.21340
2. Slingerland M, Guchelaar HJ, Gelderblom H. Liposomal drug formulations in cancer therapy: 15 years along the road. Drug Discovery Today. 2012; Feb 1; 17(3-4): 160-6. https://doi.org/10.1016/j.drudis.2011.09.015
3. Ajaykumar C. Overview on the side effects of doxorubicin. Adv. Precis. Med. Oncol. 2020 Dec 2;10.
4. Feigin VL, Stark BA, Johnson CO, Roth GA, Bisignano C, Abady GG, Abbasifard M, Abbasi-Kangevari M, Abd-Allah F, Abedi V, Abualhasan A. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet Neurology. 2021 Oct 1; 20(10): 795-820. https://doi.org/10.1016/ S1474-4422(21)00252-0
5. Kakar M, Chakarborty P, Behl T, Singh S, Sharma N, Sachdeva M. Insight into the role of inflammation in progression of diabetes associated neuropathy. Res. J. Pharm. Technol. 2020 Nov 1; 13: 5477-83.
6. Dhalendra G, Satapathy T, Roy A. Animal models for inflammation: A review. Asian Journal of Pharmaceutical Research. 2013; 3(4): 207-12.
7. Yagmurca M, Bas O, Mollaoglu H, Sahin O, Nacar A, Karaman O, Songur A. Protective effects of erdosteine on doxorubicin-induced hepatotoxicity in rats. Archives of Medical Research. 2007; May 1; 38(4): 380-5. https://doi.org/10.1016/j.arcmed.2007.01.007
8. Iwhiwhu SA, Kumar R, Khan AH, Afolabi JM, Williams JD, de la Cruz JE, Adebiyi A. A low-dose pemetrexed-cisplatin combination regimen induces significant nephrotoxicity in mice. BMC Nephrology. 2024; Oct 21; 25(1): 370. https://doi.org/10.1186/s12882-024-03822-5
9. Liu LL, Li QX, Xia L, Li J, Shao L. Differential effects of dihydropyridine calcium antagonists on doxorubicin-induced nephrotoxicity in rats. Toxicology. 2007; Feb 28; 231(1): 81-90. https://doi.org/10.1016/j.tox.2006.11.067
10. El-Moselhy MA, El-Sheikh AA. Protective mechanisms of atorvastatin against doxorubicin-induced hepato-renal toxicity. Biomedicine and Pharmacotherapy. 2014; Feb 1; 68(1): 101-10. https://doi.org/10.1016/j.biopha.2013.09.001
11. Aruna P, Gayathiri NM. Cardioprotective activity of telmisartan, metformin and its combination against doxorubicin induced myocardial infarction in rat model. Research Journal of Pharmacy and Technology. 2018; 11(12): 5293-6. http://dx.doi.org/10.5958/0974-360X.2018.00964.2
12. Jambhulkar S, Deshireddy S, Jestadi DB, Periyasamy L. Quercetin attenuating doxorubicin induced hepatic, cardiac and renal toxicity in male albino Wistar rats. Am. J. Phytomed. Clin. Ther. AJPCT. 2014; 2(8): 985-1004.
13. Virani P, Sojitra R, Raj H, Jain V. Atorvastatin: A review on analytical method and its determination in pharmaceuticals and biological matrix. Asian Journal of Pharmaceutical Analysis. 2015; 5(3): 151-60. http://dx.doi.org/10.5958/2231-5675.2015.00025.3
14. Werner N, Nickenig G, Laufs U. Pleiotropic effects of HMG-CoA reductase inhibitors. Basic Research in Cardiology. 2002; Mar; 97: 105-16.
15. Fadillioǧlu E, Erdoǧan H, Söǧüt S, Kuku I. Protective effects of erdosteine against doxorubicin‐induced cardiomyopathy in rats. Journal of Applied Toxicology: An International Journal. 2003; Jan; 23(1): 71-4. https://doi.org/10.1002/jat.889
16. Balakumar P, Rohilla A, Mahadevan N. Pleiotropic actions of fenofibrate on the heart. Pharmacological Research. 2011; Jan 1; 63(1): 8-12. https://doi.org/10.1016/j.phrs.2010.11.002
17. Cheng H, Xi Y, Chi X, Wu Y, Liu G. Fenofibrate treatment of rats with experimental autoimmune myocarditis by alleviating Treg/Th17 disorder. Central European Journal of Immunology. 2016; Jan 1; 41(1): 64-70. https://doi.org/10.5114/ceji.2016.58817
18. Walker AE, Kaplon RE, Lucking SM, Russell-Nowlan MJ, Eckel RH, Seals DR. Fenofibrate improves vascular endothelial function by reducing oxidative stress while increasing endothelial nitric oxide synthase in healthy normolipidemic older adults. Hypertension. 2012; Dec; 60(6): 1517-23. https://doi.org/10.1161/HYPERTENSIONAHA.112.203661
19. Mandlem VK, Priya NG, Raghavendra M, Abbulu K. Evaluation of Cardioprotective Activity of Tamarindus indica Linn Pericarpic extract in Doxorubicin induced Cardiotoxicity in Experimental Rats. Research Journal of Pharmacy and Technology. 2020; 13(7): 3267-73. http://dx.doi.org/10.5958/0974-360X.2020.00579.X
20. Ajith TA, Aswathy MS, Hema U. Protective effect of Zingiber officinale roscoe against anticancer drug doxorubicin-induced acute nephrotoxicity. Food and Chemical Toxicology. 2008 Sep 1; 46(9): 3178-81. https://doi.org/10.1016/j.fct.2008.07.004
21. Songbo M, Lang H, Xinyong C, Bin X, Ping Z, Liang S. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicology Letters. 2019; Jun 1; 307: 41-8. https://doi.org/10.1016/j.toxlet.2019.02.013
22. Xiang C, Yan Y, Zhang D. Alleviation of the doxorubicin-induced nephrotoxicity by fasudil in vivo and in vitro. Journal of Pharmacological Sciences. 2021; Jan 1; 145(1): 6-15. https://doi.org/10.1016/j.jphs.2020.10.002
23. Jaćević V, Dragojević-Simić V, Tatomirović Ž, Dobrić S, Bokonjić D, Kovačević A, Nepovimova E, Vališ M, Kuča K. The efficacy of amifostine against multiple-dose doxorubicin-induced toxicity in rats. International Journal of Molecular Sciences. 2018; Aug 12; 19(8): 2370. https://doi.org/10.3390/ijms19082370
24. Sari DP, Siahaan JM, Andriana H, Purwoko RY, Halim B. Cardioprotective effect of Extract Ethanol Ocimum basilicum on Rat Induced Cisplatin. Research Journal of Pharmacy and Technology. 2023; 16(12): 5770-4. http://dx.doi.org/10.52711/0974-360X.2023.00934
25. Adams SP, Tsang M, Wright JM. Lipid lowering efficacy of atorvastatin. Cochrane Database of Systematic Reviews. 2012(12).https://doi.org/10.1002/14651858.cd008226.pub2
26. Gangurde AB, Bairagi VA, Borse K. Design and quality control of fast dissolving atorvastatine calcium and amlodipine besylate tablets. Research Journal of Pharmacy and Technology. 2018; 11(6): 2424-8. http://dx.doi.org/10.5958/0974-360X.2018.00447.X
27. Virani P, Sojitra R, Savaj B, Raj H, Jain V. Simultaneous estimation of irbesartan and atorvastatin by Q absorption ratio method in their synthetic mixture. Asian Journal of Pharmaceutical Analysis. 2015; 5(1): 9-15. http://dx.doi.org/10.5958/2231-5675.2015.00002.2
28. Ghibu S, Delemasure S, Richard C, Guilland JC, Martin L, Gambert S, Rochette L, Vergely C. General oxidative stress during doxorubicin-induced cardiotoxicity in rats: absence of cardioprotection and low antioxidant efficiency of alpha-lipoic acid. Biochimie. 2012; Apr 1; 94(4): 932-9. https://doi.org/10.1016/j.biochi.2011.02.015
29. Yu FX, Zhang Y, Park HW, Jewell JL, Chen Q, Deng Y, Pan D, Taylor SS, Lai ZC, Guan KL. Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation. Genes and Development. 2013; Jun 1; 27(11): 1223-32. 10.1101/gad.219402.113
30. Ashour ML, Wink M. Genus Bupleurum: a review of its phytochemistry, pharmacology and modes of action. Journal of Pharmacy and Pharmacology. 2011; Mar; 63(3): 305-21. https://doi.org/10.1111/j.2042-7158.2010.01170.x
31. Arunkumar N, Rani C, Mohanraj KP. Formulation and In Vitro evaluation of oral floating tablets of atorvastatin calcium. Research Journal of Pharmacy and Technology. 2008; 1(4): 492-5.
32. Wani A, Chaudhary J, Jain A. A Study to Evaluate the combined effect of cromolyn Sodium and Fenofibrate in Gentamicin induced Nephropathy. Research Journal of Pharmacy and Technology. 2020; 13(7): 3215-20. http://dx.doi.org/10.5958/0974-360X.2020.00569.7
33. Li S, Gokden N, Okusa MD, Bhatt R, Portilla D. Anti-inflammatory effect of fibrate protects from cisplatin-induced ARF. American Journal of Physiology-Renal Physiology. 2005; Aug; 289(2): F469-80. https://doi.org/10.1152/ajprenal.00038.2005
34. Sugga GS, Khan MU, Khanam R. Protective role of fibrates in cardiac ischemia/reperfusion. Journal of Advanced Pharmaceutical Technology and Research. 2012; Jul 1; 3(3): 188-92. 10.4103/2231-4040.101016