Protective effects of psoralen polymer lipid nanoparticles on doxorubicin - induced myocardial toxicity
DOI:
https://doi.org/10.1590/s2175-97902022e19245Keywords:
Doxorubicin, Cadiotoxicity, Psoralen, Psoralen polymer lipid nanoparticles, AntioxidantAbstract
Doxorubicin (DOX) induced myocardial toxicity may limit its therapeutic use in clinic. Psoralen (PSO), a major active tricyclic furocoumarin extracted from Psoralea corylifolia, is widely used as an antineoplastic agent in treatment of leukemia and other cancers. This study is aim to find the protective effect of psoralen polymer lipid nanoparticles (PSO-PLN) on doxorubicin-induced myocardial toxicity in mice. The model of myocardial toxicity induced by DOX was established. The experiment was divided into 6 groups: normal saline group, DOX + Sulfotanshinone Sodium, DOX + PSO-PLN (3 mg/kg), DOX + PSO-PLN (6 mg/kg), DOX + PSO-PLN (9 mg/
kg), DOX group. DOX alone treated mice lead to a significant decrease in the body weight, heart weight, and increase in the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) markers of cardiotoxicity. However, DOX reduced glutathione (GSH) content and activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX), were recovered by PSO-PLN. And PSO-PLN also decreased markers of cardiotoxicity in the serum. Western blotting data showed that the protective effects of PSO-PLN might be mediated via regulation of protein kinase A (PKA) and p38. Our study suggest that PSO-PLN possesses antioxidant activities, inactivating PKA and p38 effect, which in turn protect the heart from the DOX-induced cardiotoxicity.
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Abushouk AI, Ismail A, Salem AMA, Afifi AM, Abdel-Daim MM. Cardioprotective mechanisms of phytochemicals against doxorubicin-induced cardiotoxicity. Biomed Pharmacother. 2017;90:935-946.
Alam MF, Khan G, Safhi MM, Alshahrani S, Siddiqui R, Sivagurunathan Moni S, et al. Thymoquinone Ameliorates Doxorubicin-Induced Cardiotoxicity in Swiss Albino Mice by Modulating Oxidative Damage and Cellular Inflammation. Cardiol Res Pract. 2018;2018:1483041.
Cao Y, Ruan Y, Shen T, Huang X, Li M, Yu W, et al. Astragalus Polysaccharide Suppresses Doxorubicin-Induced Cardiotoxicity by Regulating the PI3k/Akt and p38MAPK Pathways. Oxid Med Cell Longev. 2014;2014:674219.
Cao Y, Shen T, Huang X, Lin Y, Chen B, Pang J, et al. Astragalus polysaccharide restores autophagic flux and improves cardiomyocyte function in doxorubicin-induced cardiotoxicity. Oncotarget. 2016;8(3):4837-4848.
Chen CT, Wang ZH, Hsu CC, Lin HH, Chen JH. In Vivo Protective Effects of Diosgenin against Doxorubicin-Induced Cardiotoxicity. Nutrients. 2015;7(6): 4938-4954.
Dhalla NS, Müller AL. Protein kinases as drug development targets for heart disease therapy. Pharmaceuticals. 2010;3(7):2111-2145.
Farah R, Gilbey P, Grozovski M, Asli H, Khamisy-Farah R, Assy N. Antioxidant Enzyme Activity and Cognition in Obese Individuals with or without Metabolic Risk Factors. Exp Clin Endocrinol Diabetes. 2016;124(09):568-571.
Guo R, Lin J, Xu W, Shen N, Mo L, Zhang C, et al. Hydrogen sulfde attenuates doxorubicin-induced cardiotoxicity by inhibition of the p38 MAPK pathway in H9c2 cells. Int J Mol Med. 2013;31(3):644-650.
Gaweł S, Wardas M, Niedworok E, Wardas P. [Malondialdehyde (MDA) as a lipid peroxidation marker]. Wiad Lek. 2004;57(9-10):453-455.
Huang Q, Cai T, Li Q, Huang Y, Liu Q, Wang B, et al. Preparation of psoralen polymer-lipid hybrid nanoparticles and their reversal of multidrug resistance in MCF-7/ADR cells. Drug Deliv. 2018;25(1):1056-1066.
Hajra S, Patra AR, Basu A, Bhattacharya S. Prevention of doxorubicin (DOX)-induced genotoxicity and cardiotoxicity: Effect of plant derived small molecule indole-3-carbinol (I3C) on oxidative stress and inflammation. Biomed Pharmacother . 2018;101:228-243.
Jain A K, Swarnakar N K, Das M, Godugu C, Singh R, Poduri R, et al. Augmented anticancer efficacy of doxorubicin-loaded polymeric nanoparticles after oral administration in a breast cancer induced animal model. Mol Pharm. 2011;8(4):1140-1151.
Jiang Z, Xiong J. Induction of Apoptosis in Human Hepatocarcinoma SMMC-7721 Cells In Vitro by Psoralen from Psoralea corylifolia. Cell Biochem Biophys. 2014;70(2):1075-1081.
Kozubowski L, Lee SC, Heitman J. Signalling pathways in the pathogenesis of Cryptococcus. Cell Microbiol. 2009;11(3):370-380.
Lin M, Yin M. Preventive Effects of Ellagic Acid Against Doxorubicin-Induced Cardio-Toxicity in Mice. Cardiovasc Toxicol. 2013;13(3):185-193.
Liao P, Georgakopoulos D, Kovacs A, Zheng M, Lerner D, Pu H, et al. The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy. Proc Natl Acad Sci USA. 2001;98(21):12283-12288.
Menon S, Lawrence L, Sivaram VP, Padikkala J. Oroxylum indicum root bark extract prevents doxorubicin-induced cardiac damage by restoring redox balance. J Ayurveda Integr Med. 2018 Feb 2. pii: S0975-9476(17) 30055-4.
Maurice DH, Palmer D, Tilley DG, Dunkerley HA, Netherton SJ, Raymond DR, et al. Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system. Mol Pharmacol. 2003;64(3):533-546.
Patil L, Balaraman R. Effect of green tea extract on Doxorubicin induced cardiovascular abnormalities: antioxidant action. Iran J Pharm Res. 2012;10(1):89-96.
Shi Y, Moon M, Dawood S, McManus B, Liu PP. Mechanisms and management of doxorubicin cardiotoxicity. Herz. 2011;36(4):296-305.
Tacar O, Dass CR. Doxorubicin-induced death in tumour cells and cardiomyocytes: is autophagy the key to improving future clinical outcomes?. J Pharm Pharmacol. 2013;65(11):1577-1589.
Wang X, Wang XL, Chen HL, Wu D, Chen JX, Wang XX, et al. Ghrelin inhibits doxorubicin cardiotoxicity by inhibiting excessive autophagy through AMPK and p38-MAPK. Biochem Pharmacol. 2014;88(3):334-350.
Wu C, Sun Z, Ye Y, Han X, Song X, Liu S. Psoralen inhibits bone metastasis of breast cancer in mice. Fitoterapia. 2013;91:205-210.
Wang X, Cheng K, Han Y, Zhang G, Dong J, Cui Y, et al. Effects of psoralen as an anti-tumor agent in human breast cancer MCF-7/ADR cells. Biol Pharm Bull. 2016;39(5):815-822.
Yu J, Wang C, Kong Q, Wu X, Lu JJ, Chen X. Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products. Phytomedicine. 2018;40:125-139.
Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012;18(11):1639-1642.
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Funding data
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National Natural Science Foundation of China
Grant numbers 81273707, 81173215 -
Natural Science Foundation of Guangdong Province
Grant numbers S2013010012880, 2016A030311037 -
Guangzhou Science and Technology Program key projects
Grant numbers 2014J4500005, 201704030141 -
Department of Education of Guangdong Province
Grant numbers 2015A050502027 -
International Science and Technology Cooperation Programme
Grant numbers 2017GH16