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Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines

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Abstract

Purpose

Aloin, an anthraquinone present in the aloe species, possesses antiangiogenic, chemopreventive and antioxidant properties. It exerts cytotoxicity against breast cancer and ovarian cancer cell lines. These properties of aloin project it as a chemopreventive adjuvant to anticancer chemotherapy.

Methods

We evaluated the effect of concurrent oral administration of aloin against doxorubicin (DOX)-induced cardiotoxicity in rats. The protective effects of aloin against DOX-induced toxicity were evident as a statistically significant inhibition of a rise in the biochemical markers of myocardial damage including lactate dehydrogenase (LDH), creatinine kinase-myocardial band (CK-MB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST).

Results

Aloin dose dependently inhibited the DOX-induced changes in ECG like increased ST-height and prolonged QT interval. It protected heart against the lipid peroxidation and restored the levels of antioxidative defenses: reduced glutathione, catalase and superoxide dismutase. Aloin prominently reduced the levels of proinflammatory cytokines- TNF-α, IL-1β and IL-6. Notably, the significant protective effects of aloin were evident even at the strikingly lower doses of 1 and 5 mg/kg per day.

Conclusion

Our results highlight the necessity to further investigate the chemopreventive effects of aloin against other chemotherapeutic agents.

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References

  1. Groom Q, Reynolds T (1987) Barbaloin in aloe species. Planta Med 53(04):345–348

    CAS  PubMed  Google Scholar 

  2. Radha MH, Laxmipriya NP (2015) Evaluation of biological properties and clinical effectiveness of Aloe vera: a systematic review. J Tradit Complement Med 5(1):21–26

    PubMed  Google Scholar 

  3. Tabolacci C, Rossi S, Lentini A, Provenzano B, Turcano L, Facchiano F, Beninati S (2013) Aloin enhances cisplatin antineoplastic activity in B16–F10 melanoma cells by transglutaminase-induced differentiation. Amino Acids 44(1):293–300

    CAS  PubMed  Google Scholar 

  4. Na J, Sirdaartaa J, Cocka I (2014) The anti-proliferative properties of Australian plants with high antioxidant capacities against cancer cell lines. Pharmacogn Commun 4(4):71–82

    Google Scholar 

  5. Wamer WG, Vath P, Falvey DE (2003) In vitro studies on the photobiological properties of aloe emodin and aloin A. Free Radic Biol Med 34(2):233–242

    CAS  PubMed  Google Scholar 

  6. Tian B, Hua Y (2005) Concentration-dependence of prooxidant and antioxidant effects of aloin and aloe-emodin on DNA. Food Chem 91(3):413–418

    CAS  Google Scholar 

  7. Birari LA, Mahajan UB, Patil KR, Patil DD, Bagul NA, Belemkar S, Goyal SN, Ojha S, Patil CR (2020) Aloin protects against arsenic trioxide–induced myocardial membrane damage and release of inflammatory cytokines. Naunyn-Schmiedeberg's Archives Pharmacol 393:1–8

    Google Scholar 

  8. Kumar A, Gautam B, Dubey C, Tripathi PK (2014) A review: role of doxorubicin in treatment of cancer. Int J Pharm Sci Res 5(10):4105

    Google Scholar 

  9. Minotti G, Recalcati S, Menna P, Salvatorelli E, Corna G, Cairo G (2004) Doxorubicin cardiotoxicity and the control of iron metabolism: quinone-dependent and independent mechanisms. Methods in enzymology. Elsevier, Amsterdam, pp 340–361

    Google Scholar 

  10. Weiss RB (1992) The anthracyclines: will we ever find a better doxorubicin? Semin oncol 6:670–686

    Google Scholar 

  11. Shah S, Mohan M, Kasture S, Sanna C, Maxia A (2009) Protective effect of Ephedra nebrodensis on doxorubicin-induced cardiotoxicity in rats. Iran J Pharmacol Ther 8(2):61–60

    CAS  Google Scholar 

  12. Esmat AY, Said MM, Hamdy GM, Soliman AA, Khalil SA (2012) In vivo and in vitro studies on the antioxidant activity of aloin compared to doxorubicin in rats. Drug Dev Res 73(3):154–165

    CAS  Google Scholar 

  13. Li L, Li J, Wang Q, Zhao X, Yang D, Niu L, Yang Y, Zheng X, Hu L, Li Y (2020) Shenmai injection protects against doxorubicin-induced cardiotoxicity via maintaining mitochondrial homeostasis. Front Pharmacol 11:815

    PubMed  PubMed Central  Google Scholar 

  14. Potemski P, Polakowski P, Wiktorowska-Owczarek AK, Owczarek J, Pluzanska A, Orszulak-Michalak D (2006) Amifostine improves hemodynamic parameters in doxorubicin-pretreated rabbits. Pharmacol Rep 58(6):966

    CAS  PubMed  Google Scholar 

  15. Dragojević-Simić V, Dobrić S, Jaćević V, Bokonjić D, Milosavljević I, Kovačević A, Mikić D (2013) Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats. Vojnosanit Pregl 70(1):38–45

    PubMed  Google Scholar 

  16. Falcone G, Filippelli W, Mazzarella B, Tufano R, Mastronardi P, Filippelli A, Berrino L, Rossi F (1998) Cardiotoxicity of doxorubicin: effects of 21-aminosteroids. Life Sci 63(17):1525–1532

    CAS  PubMed  Google Scholar 

  17. Jensen RA (1986) Doxorubicin cardiotoxicity: contractile changes after long-term treatment in the rat. J Pharmacol Exp Ther 236(1):197–203

    CAS  PubMed  Google Scholar 

  18. Kelishomi RB, Ejtemaeemehr S, Tavangar SM, Rahimian R, Mobarakeh JI, Dehpour AR (2008) Morphine is protective against doxorubicin-induced cardiotoxicity in rat. Toxicology 243(1–2):96–104

    CAS  PubMed  Google Scholar 

  19. Dragojevic-Simic VM, Dobric SL, Bokonjic DR, Vucinic ZM, Sinovec SM, Jacevic VM, Dogovic NP (2004) Amifostine protection against doxorubicin cardiotoxicity in rats. Anticancer Drugs 15(2):169–178

    CAS  PubMed  Google Scholar 

  20. Cui Y, Ye Q, Wang H, Li Y, Xia X, Yao W, Qian H (2014) Aloin protects against chronic alcoholic liver injury via attenuating lipid accumulation, oxidative stress and inflammation in mice. Arch Pharmacal Res 37(12):1624–1633

    CAS  Google Scholar 

  21. Hamiza O, Rehman M, Khan R, Tahir M, Khan A, Lateef A, Sultana S (2014) Chemopreventive effects of aloin against 1, 2-dimethylhydrazine-induced preneoplastic lesions in the colon of Wistar rats. Hum Exp Toxicol 33(2):148–163

    CAS  PubMed  Google Scholar 

  22. Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ, Moens AL (2012) Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J Mol Cell Cardiol 52(6):1213–1225

    CAS  PubMed  Google Scholar 

  23. Maghamiour N, Safaie N (2014) High creatine kinase (CK)-MB and lactate dehydrogenase in the absence of myocardial injury or infarction: a case report. J Cardiovasc Thorac Res 6(1):69

    PubMed  PubMed Central  Google Scholar 

  24. Mustafa HN, Hegazy GA, El Awdan SA, AbdelBaset M (2017) Protective role of CoQ10 or L-carnitine on the integrity of the myocardium in doxorubicin induced toxicity. Tissue Cell 49(3):410–426

    CAS  PubMed  Google Scholar 

  25. Yang Y-N, Chuang Y-C, Yin W-H, Young MS (2007) Catecholamine-induced cardiomyopathy secondary to pheochromocytoma mimicking fulminant acute myocarditis. Acta Cardiologica Sinica 23(2):125–130

    Google Scholar 

  26. Xia P, Liu Y, Cheng Z (2016) Signaling pathways in cardiac myocyte apoptosis. BioMed Res Int 2016:1–22

    Google Scholar 

  27. Karamanakos PN, Pappas P, Stephanou P, Marselos M (2001) Differentiation of disulfiram effects on central catecholamines and hepatic ethanol metabolism. Pharmacol Toxicol 88(2):106–110

    CAS  PubMed  Google Scholar 

  28. Bayram C, Cetin I, Tavil B, Yarali N, Ekici F, Isık P, Tunc B (2015) Evaluation of cardiotoxicity by tissue Doppler imaging in childhood leukemia survivors treated with low-dose anthracycline. Pediatr Cardiol 36(4):862–866

    PubMed  Google Scholar 

  29. Jančić D (2016) The role of the European Parliament and the US Congress in shaping transatlantic relations: TTIP, NSA surveillance, and CIA renditions. JCMS J Common Mark Stud 54(4):896–912

    Google Scholar 

  30. Niki Y, Manzawa Y, Kametani S, Shibata T (2008) Moving-object-localization hardware algorithm employing OR-amplification of pixel activities. Jpn J Appl Phys 47(4S):2767

    CAS  Google Scholar 

  31. Zitka O, Skalickova S, Gumulec J, Masarik M, Adam V, Hubalek J, Trnkova L, Kruseova J, Eckschlager T, Kizek R (2012) Redox status expressed as GSH: GSSG ratio as a marker for oxidative stress in paediatric tumour patients. Oncol Lett 4(6):1247–1253

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Cappetta D, De Angelis A, Sapio L, Prezioso L, Illiano M, Quaini F, Rossi F, Berrino L, Naviglio S, Urbanek K (2017) Oxidative stress and cellular response to doxorubicin: a common factor in the complex milieu of anthracycline cardiotoxicity. Oxid Med Cell Longev 2017:1–13

    Google Scholar 

  33. Weydert CJ, Cullen JJ (2010) Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc 5(1):51

    CAS  PubMed  Google Scholar 

  34. Capone F, Guerriero E, Sorice A, Colonna G, Storti G, Pagliuca J, Castello G, Costantini S (2014) Synergistic antitumor effect of Doxorubicin and tacrolimus (FK506) on hepatocellular carcinoma cell lines. Sci World J 2014:1–9

    Google Scholar 

  35. Swamy AV, Gulliaya S, Thippeswamy A, Koti BC, Manjula DV (2012) Cardioprotective effect of curcumin against doxorubicin-induced myocardial toxicity in albino rats. Indian J Pharmacol 44(1):73

    CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Dist. Dhule, Shirpur, 425405, Maharashtra, India

    Lalit Birari, Shivani Wagh, Kalpesh R. Patil, Umesh B. Mahajan & Chandragouda R. Patil

  2. Pharmacology and Toxicology Division, ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, India

    Banappa Unger

  3. School of Pharmacy and Technology Management, SVKM & NMIMS, MPTP, Dist. Dhule, Shirpur, 425405, Maharashtra, India

    Sateesh Belemkar

  4. Shri Vile Parle Kelavani Mandal’s Institute of Pharmacy, Dhule, 424001, Maharashtra, India

    Sameer N. Goyal

  5. Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, P.O. Box 17666, Abu Dhabi, UAE

    Shreesh Ojha

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  1. Lalit Birari
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  2. Shivani Wagh
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  3. Kalpesh R. Patil
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  9. Chandragouda R. Patil
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Corresponding author

Correspondence to Chandragouda R. Patil.

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No conflict of interest to disclose.

Ethical approval

The study protocol was examined and approved by the Institutional Animal Ethics Committee (Reg. No. 651/PO/ReBi/S/02/CPCSEA) established under the guidelines of Committee for the Purpose of Control and Supervision of Experiments of Animals (CPCSEA), Government of India.

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Birari, L., Wagh, S., Patil, K.R. et al. Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines. Cancer Chemother Pharmacol 86, 419–426 (2020). https://doi.org/10.1007/s00280-020-04125-w

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  • DOI: https://doi.org/10.1007/s00280-020-04125-w

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