Protective effect of berberine on acute cardiomyopathy associated with doxorubicin treatment

Xiong,Chen; Wu,Yan‑Zhao; Zhang,Yu; Wu,Zi‑Xiao; Chen,Xue‑Yan; Jiang,Ping; Guo,Hui‑Cai; Xie,Ke‑Rang; Wang,Ke‑Xin; Su,Su‑Wen

doi:10.3892/ol.2018.8020

Protective effect of berberine on acute cardiomyopathy associated with doxorubicin treatment

Authors:
- Chen Xiong
- Yan‑Zhao Wu
- Yu Zhang
- Zi‑Xiao Wu
- Xue‑Yan Chen
- Ping Jiang
- Hui‑Cai Guo
- Ke‑Rang Xie
- Ke‑Xin Wang
- Su‑Wen Su
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Affiliations: Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Otorhinolaryngology‑Head and Neck Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Center for Reproductive Medicine, Family Planning Scientific and Technical Institution of Hebei Province, Shijiazhuang, Hebei 050000, P.R. China
Published online on: February 9, 2018 https://doi.org/10.3892/ol.2018.8020
Pages: 5721-5729
Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Doxorubicin (DOX) is a potent and broad‑spectrum anthracycline chemotherapeutic agent, but dose‑dependent cardiotoxic side effects limit its clinical application. This toxicity is closely associated with the generation of reactive oxygen species (ROS) radical during DOX metabolism. The present study investigated the effects of Berberine (Ber) on DOX‑induced acute cardiac injury in a rat model and analysed its mechanism in cardiomyocytes in vitro. Serum creatine kinase (CK), creatine kinase isoenzyme (CK‑MB) and malondialdehyde (MDA) levels were significantly increased in the DOX group compared with the control group. This increase was accompanied by cardiac histopathological injury and a decrease in cardiomyocyte superoxide dismutase (SOD) and catalase (CAT). CK, CK‑MB and MDA levels decreased and SOD and CAT levels increased in the Ber‑treated group compared to the DOX group. Ber ameliorated the DOX‑induced increase in cytosolic calcium concentration ([Ca2+]i), attenuated mitochondrial Ca2+ overload and restored the DOX‑induced loss of mitochondrial membrane potential in vitro. These results demonstrated that Ber exhibited protective effects against DOX‑induced heart tissue free radical injury, potentially via the inhibition of intracellular Ca2+ elevation and attenuation of mitochondrial dysfunction.

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1	Duggan ST and Keating GM: Pegylated liposomal doxorubicin: A review of its use in metastatic breast cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma. Drugs. 71:2531–2558. 2011. View Article : Google Scholar : PubMed/NCBI
2	Cortés-Funes H and Coronado C: Role of anthracyclines in the era of targeted therapy. Cardiovasc Toxicol. 7:56–60. 2007. View Article : Google Scholar : PubMed/NCBI
3	Minotti G, Menna P, Salvatorelli E, Cairo G and Gianni L: Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 56:185–229. 2004. View Article : Google Scholar : PubMed/NCBI
4	Zhang YY, Yi M and Huang YP: Oxymatrine ameliorates doxorubicin-induced cardiotoxicity in rats. Cell Physiol Biochem. 43:626–635. 2017. View Article : Google Scholar : PubMed/NCBI
5	Bordoni A, Biagi P and Hrelia S: The impairment of essential fatty acid metabolism as a key factor in doxorubicin-induced damage in cultured rat cardiomyocytes. Biochim Biophys Acta. 1440:100–106. 1999. View Article : Google Scholar : PubMed/NCBI
6	Chatterjee K, Zhang J, Honbo N and Karliner JS: Doxorubicin cardiomyopathy. Cardiology. 115:155–162. 2010. View Article : Google Scholar : PubMed/NCBI
7	Christiansen S: Clinical management of doxorubicin-induced heart failure. J Cardiovasc Surg (Torino). 52:133–138. 2011.PubMed/NCBI
8	Ludke AR, Al-Shudiefat AA, Dhingra S, Jassal DS and Singal PK: A concise description of cardioprotective strategies in doxorubicin-induced cardiotoxicity. Can J Physiol Pharmacol. 87:756–763. 2009.PubMed/NCBI
9	Tan HL, Chan KG, Pusparajah P, Duangjai A, Saokaew S, Mehmood Khan T, Lee LH and Goh BH: Rhizoma coptidis: A potential cardiovascular protective agent. Front Pharmacol. 7:362.eCollection 20162016. View Article : Google Scholar
10	Tabeshpour J, Imenshahidi M and Hosseinzadeh H: A review of the effects of Berberis vulgaris and its major component, berberine, in metabolic syndrome. Iran J Basic Med Sci. 20:557–568. 2017.PubMed/NCBI
11	National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals = Guide for the Care and Use of Laboratory Animals. 8th. Washington (DC): National Academies Press (US); 2011
12	Chen X, Zhang Y, Zhu Z, Liu H, Guo H, Xiong C, Xie K, Zhang X and Su S: Protective effect of berberine on doxorubicin induced acute hepatorenal toxicity in rats. Mol Med Rep. 13:3953–3960. 2016. View Article : Google Scholar : PubMed/NCBI
13	Kelishomi RB, Ejtemaeemehr S, Tavangar SM, Rahimian R, Mobarakeh JI and Dehpour AR: Morphine is protective against doxorubicin-induced cardiotoxicity in rat. Toxicology. 243:96–104. 2008. View Article : Google Scholar : PubMed/NCBI
14	Xiong C, Li JX, Guo HC, Zhang LN, Guo W, Meng J and Wang YL: The H₁-H₂ domain of the α1 isoform of Na+-K+-ATPase is involved in ouabain toxicity in rat ventricular myocytes. Toxicol Appl Pharmacol. 262:32–42. 2012. View Article : Google Scholar : PubMed/NCBI
15	Asensio-López MC, Soler F, Pascual-Figal D, Fernández-Belda F and Lax A: Doxorubicin-induced oxidative stress: The protective effect of nicorandil on HL-1 cardiomyocytes. PLoS One. 12:e01728032017. View Article : Google Scholar : PubMed/NCBI
16	Jain D, Ahmad T, Cairo M and Aronow W: Cardiotoxicity of cancer chemotherapy: Identification, prevention and treatment. Ann Transl Med. 5:3482017. View Article : Google Scholar : PubMed/NCBI
17	Li T, Danelisen I and Singal PK: Early changes in myocardial antioxidant enzymes in rats treated with adriamycin. Mol Cell Biochem. 232:19–26. 2002. View Article : Google Scholar : PubMed/NCBI
18	Lee IA, Hyun YJ and Kim DH: Berberine ameliorates TNBS-induced colitis by inhibiting lipid peroxidation, enterobacterial growth and NF-κB activation. Eur J Pharmacol. 648:162–170. 2010. View Article : Google Scholar : PubMed/NCBI
19	Li P, Ren J, Duan C, Lin C and Liu J: Effects of four components of Rhizoma Corydalis on anoxia and peroxidation injuries in neonatal cardiomyocytes. Zhongguo Zhong Yao Za Zhi. 35:84–88. 2010.(In Chinese). PubMed/NCBI
20	Che FF, Liu Y and Xu CG: Schisandrin B prevents doxorubicin-induced cardiotoxicity in rabbits. Sichuan Da Xue Xue Bao Yi Xue Ban. 41:24–28. 2010.(In Chinese). PubMed/NCBI
21	Li T and Singal PK: Adriamycin-induced early changes in myocardial antioxidant enzymes and their modulation by probucol. Circulation. 102:2105–2110. 2000. View Article : Google Scholar : PubMed/NCBI
22	Tong N, Zhang J, Chen Y, Li Z, Luo Y, Zuo H and Zhao X: Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro. Oncol Lett. 3:1263–1267. 2012. View Article : Google Scholar : PubMed/NCBI
23	Patil JB, Kim J and Jayaprakasha GK: Berberine induces apoptosis in breast cancer cells (MCF-7) through mitochondrial-dependent pathway. Eur J Pharmacol. 645:70–78. 2010. View Article : Google Scholar : PubMed/NCBI
24	Zhang YJ, Yang SH, Li MH, Iqbal J, Bourantas CV, Mi QY, Yu YH, Li JJ, Zhao SL, Tian NL and Chen SL: Berberine attenuates adverse left ventricular remodeling and cardiac dysfunction after acute myocardial infarction in rats: Role of autophagy. Clin Exp Pharmacol Physiol. 41:995–1002. 2014. View Article : Google Scholar : PubMed/NCBI
25	Takemura G and Fujiwara H: Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management. Prog Cardiovasc Dis. 49:330–352. 2007. View Article : Google Scholar : PubMed/NCBI
26	Hao G, Yu Y, Gu B, Xing Y and Xue M: Protective effects of berberine against doxorubicin-induced cardiotoxicity in rats by inhibiting metabolism of doxorubicin. Xenobiotica. 45:1024–1029. 2015. View Article : Google Scholar : PubMed/NCBI
27	Wang S, Konorev EA, Kotamraju S, Joseph J, Kalivendi S and Kalyanaraman B: Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms. Intermediacy of H(2)O(2)- and p53-dependent pathways. J Biol Chem. 279:25535–25543. 2004. View Article : Google Scholar : PubMed/NCBI
28	Solem LE, Henry TR and Wallace KB: Disruption of mitochondrial calcium homeostasis following chronic doxorubicin administration. Toxicol Appl Pharmacol. 129:214–222. 1994. View Article : Google Scholar : PubMed/NCBI
29	Zorzato F, Sarviati G, Facchinetti T and Volpe P: Doxorubicin induces calcium release from terminal cisternae of skeletal muscle. A study on isolated sarcoplasmic reticulum and chemically skinned fibers. J Biol Chem. 260:7349–7355. 1985.PubMed/NCBI
30	Kim DH, Landry AB III, Lee YS and Katz AM: Doxorubicin-induced calcium release from sarcoplasmic reticulum vesicles. J Moll Cell Cardiol. 21:433–436. 1989. View Article : Google Scholar
31	Caroni P, Villani F and Carafoli E: The cardiotoxic antibiotic doxorubicin inhibits the Na+/Ca2+ exchange of dog heart sarcolemmal vesicles. FEBS Lett. 130:184–186. 1981. View Article : Google Scholar : PubMed/NCBI
32	Keung EC, Toll L, Ellis M and Jensen RA: L-type cardiac calcium channels in doxorubicin cardiomyopathy in rats morphological, biochemical, and functional correlations. J Clin Invest. 87:2108–2113. 1991. View Article : Google Scholar : PubMed/NCBI
33	Przygodzki T, Sokal A and Bryszewska M: Calcium ionophore A23187 action on cardiac myocytes is accompanied by enhanced production of reactive oxygen species. Biochim Biophys Acta. 1740:481–488. 2005. View Article : Google Scholar : PubMed/NCBI
34	Petrosillo G, Ruggiero FM, Pistolese M and Paradies G: Ca2+-induced reactive oxygen species production promotes cytochrome c release from rat liver mitochondria via mitochondrial permeability transition (MPT)-dependent and MPT-independent mechanisms: Role of cardiolipin. J Biol Chem. 279:53103–53108. 2004. View Article : Google Scholar : PubMed/NCBI
35	Waring P: Redox active calcium ion channels and cell death. Arch Biochem Biophys. 434:33–42. 2005. View Article : Google Scholar : PubMed/NCBI
36	Li L, Takemura G, Li Y, Miyata S, Esaki M, Okada H, Kanamori H, Khai NC, Maruyama R, Ogino A, et al: Preventive effect of erythropoietin on cardiac dysfunction in Doxorubicin-induced cardiomyopathy. Circulation. 113:535–543. 2006. View Article : Google Scholar : PubMed/NCBI
37	Yeh YC, Lai HC, Ting CT, Lee WL, Wang LC, Wang KY, Lai HC and Liu TJ: Protection by doxycycline against doxorubicin-induced oxidative stress and apoptosis in mouse testes. Biochem Pharmacol. 74:969–980. 2007. View Article : Google Scholar : PubMed/NCBI
38	Rahn CA, Bombick DW and Doolittle DJ: Assessment of mitochondrial membrane potential as an indicator of cytotoxicity. Fundam Appl Toxicol. 16:435–448. 1991. View Article : Google Scholar : PubMed/NCBI
39	Lv X, Yu X, Wang Y, Wang F, Li H, Wang Y, Lu D, Qi R and Wang H: Berberine inhibits doxorubicin-triggered cardiomyocyte apoptosis via attenuating mitochondrial dysfunction and increasing Bcl-2 expression. PLoS One. 7:e473512012. View Article : Google Scholar : PubMed/NCBI