2018 Volume 5 Issue 3

Hawthorn Leaves Extract Suppress the Cardiotoxicity-induced by Doxorubicin in Rats: Mechanistic Study

Arwa M. Turkistani

Cardiovascular diseases from the primary death causes worldwide. Doxorubicin (DOXO) consider one from the most widely and potent anticancer drugs. Free radicals are responsible for cardiotoxicity induced by DOXO. Hawthorn leaf has potent antioxidant, anti-cardiac remodeling, vasodilating, anti-inflammatory and anti-reperfusion/ischemia injury. The current work was aimed to investigate the possible action of hawthorn leaves methanolic extract (HLME) on the damage effects of DOXO in heart tissue. Adult male rats (n=40) were equally divided into 4 groups; Control (Con), DOXO, HLME and HLME+ DOXO groups. The HLME (400 mg/kg) was administrated for 3 weeks before intraperitoneal (i.p) injection with DOXO (20 mg /kg, single dose). Serum cardiac function enzymes, cardiac antioxidant biomarkers and serum inflammatory biomarkers were determined. As well as the cardiac muscle in all groups were histopathologically examined. Pre-treatment with HLME significantly lowered the elevated serum cardiac function activities and inflammatory cytokine biomarkers, as well as ameliorated cardiac antioxidant biomarkers via decreasing oxidative stress and increasing antioxidant status. The histopathological examination of cardiac muscle tissue confirmed these results. Therefore, the HLME has cardio protection effect against DOXO induced cardiotoxicity in rats, this effect could be explained via antioxidant and anti-inflammatory properties.


Slingerland, M., Guchelaar, H.J. and Gelder-blom, H. (2012). Liposomal drug formula-tions in cancer therapy: 15 years along the road. Drug Disco, 17:160 6.

Fernandez-Chas M., Curtis M.J. and Niederer S.A. (2018). Mechanism of doxorubicin car-diotoxicity evaluated by integrating multiple molecular effects into a biophysical mod-el. Br J Pharmacol., 175: 763–781.

Zhu, J., Zhang,J and ,Zhang,L. (2011). Inter-leukin-1 signaling mediates acute doxorubi-cin-induced cardiotoxicity. Biomed Pharma-cotherapy, 65(7): 481–485.

Guo, R., Wu, K., Chen, J., Mo, L., Hua, X., Zheng, D., Chen, P., Chen, G., Xu, W. and Feng, J.(2013). Exogenous hydrogen sul-fide protects against doxorubicin-induced in-flammation and cytotoxicity by inhibiting p38MAPK/NFκB pathway in H9c2 cardiac cells. Cell Physiol Biochem., 32(6):1668-80.

Hosseini, A., Bakhtiari, E. and Mousavi, S.H. (2017). Protective effect of Hibiscus sabdar-iffa on doxorubicin-induced cytotoxicity in H9c2 Cardiomyoblast Cells. Iran. J. Pharm. Res., 16, 708–713.

Yilmaz, S., Atessahin, A., Sahna, E., Karahan, I. and Ozer, S. (2006). Protective effect of ly-copene on adriamycin-induced cardiotoxici-ty and nephrotoxicity. Toxicology, 218:164–171.

Hamza, A., Amin,A and Daoud,S. (2008). The protective effect of a purified extract of withania somnifera against doxorubicin-induced cardiac toxicity in rats. Cell Biol Toxicol., 42:63–73.

Li, W., Xu, B., Xu, J. and Wu, L. (2009). Procyanidins produce significant at-tenuation of doxorubicin-induced cardiotoxi-city via suppression of oxidative stress. Basic Clin Pharmacol Toxi-col.104:192–197.

Diane, A., Borthwick, F., Wu, S., Lee, J., Brown, P. N., Dickinson, T. A., Croft, K. D., Vine, D. F. and Proctor, S. D. (2016). Hypoli-pidemic and cardioprotective benefits of a novel fireberry hawthorn fruit extract in the JCR:LA-cp rodent model of dyslipidemia and cardiac dysfunction. Food Funct., 7: 3943–3952.

Koch, E., and Malek, F. A. (2011). Standard-ized extracts from hawthorn leaves and flowers in the treatment of cardiovascular disorders- preclinical and clinical studies. Planta Med., 77: 1123–1128.

Dahmer, S. and Scott, E. (2010) Health effects of hawthorn. Am Fam Physician., 81: 465–468.

Chang, M. Zhu, Z. Zuo, M and Chow, W.K. (2001). High-performance liquid chromato-graphic method for simultaneous determina-tion of hawthorn active components in rat plasma. J Chromatogr Biomed Sci Appl., 760: 227-235.

Sowndhararajan, K. and Kang, S.C. (2013). Free radical scavenging activity from differ-ent extracts of leaves of Bauhinia vahlii Wight & Arn. Saudi J Biol Sci., 20(4):319-25.

Chahardahcharic, S.V. and Setorki, M. (2018). The effect of hydroalcoholic extract of Cra-taegus monogyna on hyperglycemia, oxida-tive stress and pancreatic tissue damage in streptozotocin-induced diabetic rats. J Herbmed Pharmacol., 7(4): 294-299.

Rezaei-Golmisheh, A., Malekinejad, H., Asri-Rezaei, S., Farshid, A.A. and Akbari, P. (2015). Hawthorn ethanolic extracts with triterpenoids and flavonoids exert hepato-protective effects and suppress the hyper-cholesterolemia‐induced oxidative stress in rats. Iran J Basic Med Sci. 18(7):691-699

El-Agamy, D. S., Abo-Haded, H. M. and Elka-blawy, M. A. (2016). Cardioprotective effects of sitagliptin against doxorubicin-induced cardiotoxicity in rats. Experimental Biol and Med., doi.org/10.1177/1535370216643418.

Bancraft, J.D., Stevens, A. and Turner, D.R. (1996). Theory and Practice of Histological Techniques. Fourth Ed. New York, London, San Francisco, Tokyo: Churchill Livingstone.

Al-Kuraishy, H. M., Mohammed, M. A. and Khaleel,S. (2015). Significant attenuation and amelioration effects of labetalol in doxorubi-cin induced cardiotoxicity. An animal model study. J Cardiovascular Surg, 3 (2): 25-29.

AlKuraishy , H. M. and Al-Gareeb, A.I. (2015). Cardio-protective effects of cyclosporine in doxorubicin induced cardiotoxicity and as-sessment of Interleukin-17 as biomarker of cardiac injury: an animal model study. Adv. Biomed. Pharma., 2( 3):138-145.

Iqbal, M. K., Dubey, T., Anwer, A. and Pillai, K. K. (2008). Protective effects of telmisartan against acute doxorubicin-induced cardiotox-icity in rats. Pharmacological Reports, 60 (3): 382-389.

Dragojevic-Simic, V.M., Dobric SL, Bokonjic, D.R., Vucinic, Z.M., Sinovec, S.M., Jacevic, V.M. and Dogovic, N.P. (2004). Amifostine protection against doxorubicin cardiotoxicity in rats. Anticancer Drugs, 15:169–178.

Atli, O. S. Ilgin, H. Altuntas,O. and Bu-rukoglu,D. (2015). Evaluation of azithromy-cin induced cardiotoxicity in rats. Intern J of Clin and Experiment Med., 8( 3): 3681–3690.

Bruce, J. (2010). Plasma membrane calcium pump regulation by metabolic stress. World J Biol Chem., 1 (7): 221-228.

Nagi, M.N. and Mansour,M.A.( 2000). Protec-tive effect of thymoquinone against doxoru-bicin-induced cardiotoxicity in rats: a possi-ble mechanism of protection. Pharmacol Res., 41 (3): 283-289.

Gianni, L., Zweier, J.L, Levy, A.and Myers, C.E. (1985). Characterization of the cycle of iron-mediated electron transfer from doxo-rubicin to molecular oxygen. J Biol Chem., 259:6056-8.

Olson, R.D. and Mushlin, P.S. (1990). Doxo-rubicin cardiotoxicity: analysis of prevailing hypothesis. FASEB. J., 4:3076-86.

Alderton, P.M., Gross, J. and Green, M.D. (1992). Comparative study of doxorubicin, mitoxantrone, and epirubicin in combination with ICRF-187 (ADR-529) in a chronic cardi-otoxicity animal model. Cancer Res., 52:194-201.

Rossi, F., Filippelli, W., Russo, S., Filippelli, A. and Berrino, L. (1994). Cardiotoxicity of doxorubicin: effects of drugs inhibiting the release of vasoactive substances. Pharm Tox., 75:99-107.

Vásquez-Vivar, J., Martasek, P., Hogg, N. and Masters, B.S. (1997). Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochem Pharmacol., 36:11293-7.

Luo, X., Evrovsky, Y., Cole, D., Trines, J., Ben-son, L.N. and Lehotay, D.C. Doxorubicin-induced acute changes in cytotoxic alde-hydes, antioxidant status and cardiac func-tion in the rat. Biochim. Biophys. Acta., 1360:45-52.

Cui, T., Li, J., Kayahara, H., Ma, L., Wu, L. and Nakamura, K. (2006). Quantification of the polyphenols and triterpene acids in haw-thorn by high-performance liquid chroma-tography. J of Agri and Food Chem., 54(13), 4574–4581.

Ali,S.J. and Shapour, H.(2013). Crataegus monogyna fruit aqueous extract as a protec-tive agent against doxorubicin-induced re-productive toxicity in male rats. Avicenna J Phytomed., 3(2): 159–170.

Shatoor, A.S.( 2012). Cardio-tonic effect of the aqueous extract of whole plant of Cratae-gus aronia syn:azarolus (L) on isolated rab-bit’s heart. Afri J Pharmacy and Pharmacol., 6 (26): 1901-1909.

Shatoor, A.S. (2011). Acute and sub-acute toxicity of Crataegus Aronia Syn. Azarolus (L.) whole plant aqueous extract in wistar rats. Am J of Pharmacol and Toxicol., 6 (2): 37-45.

Shatoor, A.S., Soliman, F., Al-Hashem, B.E., Gamal, A., Othman, N. and El-Menshawy, A. (2012). Effect of Hawthorn (Crataegus aro-nia syn. azarolus (L)) on platelet function in albino Wistar rats. Thrombosis Res., 130 (1): 75–80.

Shatoor, A.S. (2013). In vivo hemodynamic and electrocardiographic changes following Crataegus aronia syn. Azarolus (L) admin-istration to normotensive Wistar rats. Saudi Med J., 34 (2) 179-190.

Kalay, N., Basar, I., Ozdogru, O., Er, Y., Cetinkaya, A., Dogan, T., Inanc, A., Oguzhan , N.K., Eryol , R., Topsakal,d. and Ergin, A. (2006). Protective effects of carvedilol against anthracycline-induced cardiomyopa-thy. J of the Am College of Cardiol., 48 (11): 2258-2262.

Cardinale, D., Colombo, M.T., Sandri, G., Lamantia, N., Colombo, M., Civelli, G., Marti-nelli, F.,Veglia, C., Fiorentini, C.M. and Cipol-la,D. (2006). Prevention of high-dose chemo-therapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation, 114 (23):2474-2482.

Entomology and Applied Science Letters is an international peer reviewed publication which publishes scientific research & review articles related to insects that contain information of interest to a wider audience, e.g. papers bearing on the theoretical, genetic, agricultural, medical and biodiversity issues. Emphasis is also placed on the selection of comprehensive, revisionary or integrated systematics studies of broader biological or zoogeographical relevance. Papers on non-insect groups are no longer accepted. In addition to full-length research articles and reviews, the journal publishes interpretive articles in a Forum section, Short Communications, and Letters to the Editor. The journal publishes reports on all phases of medical entomology and medical acarology, including the systematics and biology of insects, acarines, and other arthropods of public health and veterinary significance.
Issue 2 Volume 7 - 2020
Call for Papers
Entomology and Applied Science Letters supports the submission of entomological papers that contain information of interest to a wider reader groups e. g. papers bearing on taxonomy, phylogeny, biodiversity, ecology, systematic, agriculture, morphology. The selection of comprehensive, revisionary or integrated systematics studies of broader biological or zoogeographical relevance is also important. Distinguished entomologists drawn from different parts of the world serve as honorary members of the Editorial Board. The journal encompasses all the varied aspects of entomological research. This has become the need felt in scientific research due to the emphasis on intra-, inter-, and multi-disciplinary approach.