Efek Protektif Andrografolid terhadap Kejadian Kardiotoksisitas Pasca Aplikasi Doksorubisin pada Tikus


Sri Wahyuni Salam(1*), Agus Setiyono(2), Vetnizah Juniantito(3)

(1) Fakultas Kedokteran Hewan, Institut Pertanian Bogor
(2) Fakultas Kedokteran Hewan, Institut Pertanian Bogor
(3) Fakultas Kedokteran Hewan, Institut Pertanian Bogor
(*) Corresponding Author


Cardiotoxicity is one of the important side effects of doxorubicin, an anthracycline antibiotic and chemotherapeutic drug. The aim of this study was to explore the potential protective effect of andrographolide (Andro), an anti-inflammatory and anti-oxidant agents, against cardiotoxicity induced by doxorubicin (DXR). Thirty Sprague Dawley rats (80-100 g) were divided into four groups: (a) Control (b) DXR (4 mg/kg intraperitoneally (IP) were made weekly for 4 weeks), (c) DXR+Andro20 (low dose andro; 20 mg/kg IP were
made daily for 4 weeks, 24 h after DXR), (d) DXR+Andro100 (high dose andro; 100 mg/kg IP were made daily for 4 weeks, 24 h after DXR). Furthermore, at the end of experimental period, all rats were euthanized and hearts were removed for hispatological analyses. Hematoxylin-eosin (HE) and Masson Trichrome (MT) staining were used to observe the histomorphological alterations and fibrosis of hearts, respectively. Our results showed that andrographolide treatment (20 mg/kg) augmented the detrimental effects of DXR such as decreased body weight and heart weight, as compared with those in DXR-treated rats. Histopathologically, heart tissue from control group showed compact myocardial architecture without any noticeable lesions. Histopathological analysis from
DXR group showed severe inflammation and fibrosis, whereas DXR+Andro20 group showed almost normal heart morphology. Andrographolide at a dosage of 100 mg/kg did not show protective effects against doxorubicin,
and even aggravated myocardial inflammation, as compared with DXR-treated rats. These results indicate that low dose of andrographolide compromised doxorubicin-induced decreased body weight, heart inflammation, and


Andrographolide; doxorubicin; cardiotoxicity; cardiac fibrosis; rat

Full Text:



Abu-Ghefreh, A.A., Canatan, H. and Ezeamuzie, C.I. (2009). In vitro and in vivo antiinflammatory effects of andrographolide. Int.

Immunopharmacol. 9 (3): 313-318.

Arozal, W., Suyatna, F.D., Juniantito, V., Rosdiana,D.S., Amurugam, S., Aulia, R., Monayo,E.R. and Siswandi, R. (2014). The effects

of mangiferin (Mangifera indica L) indoxorubicin-induced cardiotoxicity in rats.Drug Res. 64: 1-7.

Fadillioglu, E., Erdogan, H., Sogut, S. and Kuku, I.(2003). Protective effects of erdosteine againstdoksorubisin induced cardiomyopathy in rats.J. Appl. Toxicol. 23 (1): 71-74.

Jayakumar, T., Hsieh, C.Y., Lee, J.J. and Sheu,J.R. (2013). Experimental and clinical pharmacology of Andrographis paniculata

and its major bioactive phytoconstituent andrografolid. eCAM J. 1-16.

Huojun, Z. and Jianyun, Y. (2007). Literature analysis of allergic reactions caused by lianbizhi injection in 87 cases. CNKI J. 9:025.

Lee, T.Y., Chang, H.H., Wen, C.K., Huang, T.H. and Chang, Y.S. (2014). Modulation of thioacetamide-induced hepatic inflammations,

angiogenesis and fibrosis by andrographolide in mice. J. Ethnopharmacol. 158: 423-430.

Martha, J.W., Surianata, S. dan Santoso, A. (2007). Gambaran fungsi diastolik ventrikel kiri pada penderita keganasan yang mendapat kemoterapi doksorubisin. JKI. 28 (5): 320-326.

Nakamura, T., Ueda, Y., Juan, Y., Katsuda, S.,Takahashi, H. and Koh, E. (2000). Fasmediated apoptosis in andriamycin-induced

cardiomyopathy in rats. AHA J. 102: 573-578.

Neha, P., Trivedi, Rawal, U.M, and Patel, B.P. (2007). Hepatoprotective effect of andrographolide against exachlorocyclohexane-induced oxidative injury. Integr. cancer ther. 6 (3):271-280.

Peng, X., Chen, B., Lim, C.C. and Sawyer, D.B. (2005). The cardiotoxicity of antrasiklin chemotherapeutic: translating molecular into preventive medicine. Mol. Interv. 5 (3): 163-171.

Schulke, K.J., Coyle, L., Merrill, G.F. and Denhardt,D.T. (2013). Acetaminophen attenuates doxorubicin-induced cardiac fibrosis via

osteopontin and GATA4 regulation: reduction of oxidant levels. J. Cell. Physio. 228: 2006-2014.

Siahaan, I.H., Tobing, T.C., Rosdiana, N. dan Lubis, B. (2007). Dampak kardiotoksik obat kemoterapi golongan antrasiklin. Sari Pediatri 9 (2): 151-156.

Tacar, O., Sriamornsak, P. and Dass, C.R. (2013). Doksorubisin: an update on anti cancer molecular action, toxicity and novel drug

delivery systems. J. Pharm. Pharmacol. 65:157-170.

Xia, Y.F., Ye, B.Q., Li, Y.D., Wang, J.G., He, X.J.,Lin, X., Yao, X., Ma, D., Slungaard, A.,Hebbel, P., Key, N.S. and Geng, J.G. (2004).

Andrographolide attenuates inflammation by inhibition of NF-Κb activation through covalent modivication of reduced cysteine 62

of p50. J. Immunol. 173: 4207-4217.

Zhao, W., Zhao, T., Chen, Y., Ahokas, R.A. and Sun,Y. (2008). Oxidative stress mediates cardiac fibrosis by enhancing transforming growth factor-beta1 in hypertensive rats. Moll. Cell. Biochem. 317: 43-50.

Zhu, T., Zhang, W., Xian, M., Chen, H. and Jin, H. (2013). Protective role of andrografolid in bleomycin-induced pulmonary fibrosis in

mice. Int. J. Mol. Sci. 14: 23581-23596.

Zhonghui, H., Quanjun, Q. and mingyang, L. (2009).Nephrotoxicity of andrographolide injection and its safe use. ADRJ. 11 (1): 28-30.

DOI: https://doi.org/10.22146/jsv.27569

Article Metrics

Abstract views : 2462 | views : 3382


  • There are currently no refbacks.

Copyright (c) 2017 Jurnal Sain Veteriner

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Jurnal Sain Veteriner Indexed by


Copyright of JSV (Jurnal Sain Veteriner) ISSN 0126-0421 (print), ISSN 2407-3733 (online).

Fakultas Kedokteran Hewan, Universitas Gadjah Mada

Jl. Fauna No.2, Karangmalang, Yogyakarta

Phone: 0274-560862

Fax: 0274-560861

Email: jsv_fkh@ugm.ac.id

HP. 0895363078367

Jurnal Sain Veteriner is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.


web stats View My Stats