Antigenotoxicity Activity of Papaya (Carica papaya L.) Leaf Ethanolic Extract on Swiss Mice Induced Cyclophosphamide through Mammalian In Vivo Micronucleus Test

Bani Adlina Shabrina, Juang Juansa, Nindya Budiana Putri, Rohmad Yudi Utomo, Retno Murwanti

Abstract


Cyclophosphamide (CPA) is an effective chemotherapeutic agent, but has side effect, causing DNA damage (genotoxic). Papaya leaf (Carica papaya L.) is known has flavonoid compound, quercetin. Quercetin is known has DNA protecting effect (antigenotoxic effect) by metabolism modulation. Thus, the aim of this research is to investigate the antigenotoxic effect of ethanolic extract of papaya (Carica papaya L.) leaf (EEPL) on CPA induced mice. The antigenotoxic effect was evaluated by mammalian in vivo micronucleus test. EEPL was orally administered as single treatment at dose 1000 mg/kgBW and in combination with CPA 50 mg/kgBW at dose 250 mg/kgBW; 500 mg/kgBW; and 1000 mg/kgBW. Molecular docking using PLANTS on CYP 3A4 was performed to explore the antigenotoxic effect mechanism. The three different combination dose of EEPL with CPA significantly (P<0.05) decreased the amount of micronucleated polychromatic erytrhocyte (MNPCE)/1000 polychromatic erythrocyte (PCE) and also increased % PCE/(PCE+normochromatic erythrocyte (NCE)), compared with single dose of CPA. Nevertheless, the antigenotoxic effect wasn’t significant compared with each combination dose. The docking score result showed quercetin (-82,41) has more potent interaction to CYP 3A4 than cyclophosphamide (-70,16) and both of them has similar active site at amino acid residue Ile 369 and Thr 309. The results obtained indicated that EEPL at dose 250 mg/KgBB is the optimal dose as antigenotoxic agent by interaction between quercetin with CYP 3A4 based on molecular docking.

Keywords: antigenotoxic, Carica papaya L., MNPCE, in vivo


Full Text:

PDF

References


Kastan, M.B. and Bartek, 2004, J. Cell-cycle Checkpoints and Cancer, Nature, 432(7015),316-323. CrossRef

Canini, A., Daniela, A., Giuseppe, D. and Pietro, T., 2007, Gas Chromatography Mass Spectrometry Analysis of Phenolic Compounds from Carica Papaya L. Leaf. J. Food Compost. Anal., 20(7)584–590. CrossRef

Criswell, K.A., Krishna, G., Zielinski, D., Urda, G.A., Theiss, J.C., Juneau, P., et al., 1998, Use of Acridine Orange in: Flow Cytometric Assessment of Micronuclei Induction, Mutat. Res., 414(1-3),63-75. Link

Ruddon, 2007. Cancer Biology 4th Edition. Oxford University Press.

Shukla, S., Nguyen, A., Thorn, C., Flockhart, D., McLeod, H. and Wainer, I., 2001, Model human liver cell showing genes involved in the metabolisme of cyclophosphamide: Cyclophosphamide Pathway, Link

Srinivas, H.R., Talkad, M.S., Ishwarya, M.S., Samreen, S., Sharvani. and Umesh, H.R., 2013, Effect Of Quercetin on Micronucleus Study in Mice, Int. J. Life Sci. Pharma. Res., 2(3),257-263. Link

Utesch, D., Feige, K., Dasenbrock, J., Broschard, T. H., Harwood, M., Danielewska-Nikiel, B., et al., 2008, Evaluation of the Potential In vivo Genotoxicity of Quercetin, Mutat. Res., 654(1), 38–44. CrossRef




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev7iss1pp31-37

Copyright (c) 2017 Indonesian Journal of Cancer Chemoprevention

Indexed by:

               

               

      

 

Indonesian Society for Cancer Chemoprevention