Genotoxic and chemopreventive potentials of ethanol leaves extract of Annona muricata on N-Ethyl-N-Nitrosourea-induced pro-leukaemia carcinogen in mice model by bone marrow micronucleus assay

Oluwaseyi Bamisaye; Anthony Fashina; Fatai Abdulraheem; Olufemi Emmanuel Akanni; Fadiora S. Olufemi

doi:10.20883/medical.e760

Authors

Oluwaseyi Bamisaye Department of Biomedical Laboratory Science, Faculty of Basic Medical Science, College of Medicine, University of Ibadan https://orcid.org/0000-0003-2741-2809
Anthony Fashina Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
Fatai Abdulraheem Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
Olufemi Emmanuel Akanni Department of Medical Laboratory Science, College of Health Sciences, Osun State University, Osogbo, Nigeria. https://orcid.org/0000-0003-4572-7986
Fadiora S. Olufemi Department of Surgery, College of Health Sciences, Osun State University, Osogbo, Nigeria https://orcid.org/0000-0002-6784-6196

DOI:

https://doi.org/10.20883/medical.e760

Keywords:

Genotoxicity, Leukaemia, Annona muricata

Abstract

Background. Studies have proven the effect of several agents, including natural products, to induce, prevent and treat genotoxicity through experimental models and clinical trials. In this study, the genotoxic preventive potential of Annona muricata ethanol extract on N-Ethyl-N-Nitrosourea (ENU)-induced pro-leukaemia in mice models using micronuclei formation in bone marrow was assessed.

Materials and methods. Forty-eight mice weighing 18-24g were randomly divided into six groups of eight mice. The mice were intravenously administered 20mg/kg of NEU 48 hourly 3 times, 80mg/kg of NEU 48 hourly 3 times. The negative control was fed with feed and water only. We introduced 0.2ml (0.1g/ml) ethanolic extract of Annona muricata for 3 weeks prior to NEU low dosage administration, 0.2ml (0.1g/ml) ethanolic extract of Annona muricata for 3 weeks prior to ENU high dosage and Annona muricata (ethanolic extract) administration, and gave commercial diet to the adverse/ toxicity group. The bone marrow was harvested, smeared and stained using MayGrumwald. The procedure enabled the determination of micronucleus polychromatic erythrocytes (MNPCEs) microscopically.

Results. Groups exposed to various dosages of the ENU yielded significantly increased MNPCEs, with group B producing higher MNPCEs. The groups treated with the extract displayed a significant reduction in the MNPCEs despite prior exposure to concentrations of NEU. The adverse group displayed no difference in MNPCEs compared with the negative control.

Conclusion. The ENU induced genotoxicity depending on its concentration. The extract displayed a profound capacity to prevent genotoxicity and alleviate leukaemia with good tolerance.

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References

Adalberto M., Marion P., Jacques F., Isabelle S., Alain M. and Freddie B., Epidemiological patterns of leukaemia in 184 countries: a population based study. The Lancet Haematology.2018; 5(1):14–24.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: gLOBOCAN estimates of incidence and mortality. worldwide for 36 cancers in 185 countries. CA J Clin. 2018; 68(6):394–424. DOI: https://doi.org/10.3322/caac.21492

Dong Y., Shi O., Zeng Q. et al. Leukemia incidence trends at the global, regional, and national level between 1990 and 2017. Exp Hematol Oncol .2020; 9( 14). doi.org/10.1186/s40164-020-00170-6 DOI: https://doi.org/10.1186/s40164-020-00170-6

Miranda-Filho A, Piñeros M, Ferlay J, Soerjomataram I, Monnereau A, Bray F. Epidemiological patterns of leukaemia in 184 countries: a population-based study. Lancet Haematol. 2018;5(1):e14-e24. doi: 10.1016/S2352-3026(17)30232-6. PMID: 29304322. DOI: https://doi.org/10.1016/S2352-3026(17)30232-6

Paul Rawlinson (2019).Introduction to Genotoxicity In : Gentronix.Gentronix limited, Cheshire. https://gentronix.co.uk/an-introduction-to-genotoxicity/

Christopher W. In-Process Control Testing ,In: Separation Science and Technology, Editor(s): Satinder Ahuja, Stephen Scypinski, Academic Press, 10, 2011: 397-427. doi.org/10.1016/B978-0-12-375680-0.00010-3. DOI: https://doi.org/10.1016/B978-0-12-375680-0.00010-3

Aliyu A., Shaari M., Mustapha N., Sayuti N., Reduan M.F., Sithambaram S., Shaari K., and Hamzah H. Some Chemical Carcinogens for Leukaemia Induction AND THEIR Animal Models. Annual Research and Review in Biology.2019; 33(1):1-7. DOI: https://doi.org/10.9734/arrb/2019/v33i130108

Boyonoski AC, Jennifer CS, Lisa MG, Jacobs RM, Shah GM, Poirier GG., Kirkland JB. Niacin deficiency Decreases Bone Marrow Poly (ADP-Ribose) and the Latency of Ethyinitrosourea-Induced Carcinogenesis in Rats. The Journal of Nutrition.2002; 132(1): 108-114. DOI: https://doi.org/10.1093/jn/132.1.108

Aliyu A, Shaari MR, Ahmad Sayuti NS, Reduan MFH, Sithambaram S, Noordin MM, Shaari K, Hamzah H. N-Ethyl-n-Nitrosourea Induced Leukaemia in a Mouse Model through Upregulation of Vascular Endothelial Growth Factor and Evading Apoptosis. Cancers (Basel). 2020; 12(3):678. doi: 10.3390/cancers12030678. PMID: 32183192; PMCID: PMC7140055 DOI: https://doi.org/10.3390/cancers12030678

Chen T, Mei N, Fu PP. Genotoxicity of pyrrolizidine alkaloids. J. Appl. Toxicol. 2010;30:183-196. DOI: https://doi.org/10.1002/jat.1504

Mei, N., Guo, X., Moore, M.M., Methods for using the mouse lymphoma assay to screen for chemical mutagenicity and photo-mutagenicity. In: Caldwell, G.W., Yan, Z. (Eds.), Optimization in Drug Discovery: In Vitro Methods. Humana Press, New York, 2014:561-592. DOI: https://doi.org/10.1007/978-1-62703-742-6_34

Nan M, Xilin L, Si C, Lei G, Xiaoqing G. Genotoxicity evaluation of nutraceuticals. In Nutraceuticals Efficacy, Safety, and Toxicity. In Ramesh G.,Raji L. Ajay S. Second Ed.Academic Press Elsevier 2021; 71: 1199-1211. DOI: https://doi.org/10.1016/B978-0-12-821038-3.00071-9

Urruticoechea A, Alemany R, Balart J, Villanueva A, Viñals F, Capellá G. Recent advances in cancer therapy: An overview. Current Pharmaceutical Design. 2010; 16: 3-10. DOI: https://doi.org/10.2174/138161210789941847

Petrovska, BB. Historical review of medicinal plants’ usage. Pharmacogn. Rev. 2012; 6: 1-5. DOI: https://doi.org/10.4103/0973-7847.95849

Mei N., Guo, X., Ren, Z., et al. Review of Ginkgo biloba-induced toxicity, from experimental studies to human case reports. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 2017; 35: 1-28. DOI: https://doi.org/10.1080/10590501.2016.1278298

Akanni EO, Faremi A, Adekemi AR, Bamisaye EO, Adewumi FA, Agboola OA, Liasu OI. African Polyherbal Formulation Possesses Chemopreventive and Chemotherapeutic Effects on Benzene- Induced Leukemia in Wistar Rats. Annual Research & Review in Biology. 2017; 16(2): 1-11. DOI: https://doi.org/10.9734/ARRB/2017/34773

Dwyer JT, Coates PM. Why Americans need information on dietary supplements. J. Nutr. 2018; 148: 1401S-1405S. DOI: https://doi.org/10.1093/jn/nxy081

WHO traditional medicine strategy 2014-2023. ,http://apps.who.int/iris/bitstream/10665/92455/1/9789241506090_eng.pdf?ua51. (Accessed 21 November, 2021).

Yang C, Gundala SR, Mukkavilli R, Vangala S, Reid MD, Aneja R. Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer. Carcinogenesis. 2015;36(6):656-65. doi: 10.1093/carcin/bgv046. PMID: 25863125; PMCID: PMC4566098. DOI: https://doi.org/10.1093/carcin/bgv046

Adewole SO, Ojewole JA. Protective effects of Annona muricata Linn. (Annonaceae) leaf aqueous extract on serum lipid profiles and oxidative stress in hepatocytes of streptozotocin-treated diabetic rats. Afr J Tradit Complement Altern Med. 2008 ; 6(1):30-41. DOI: https://doi.org/10.4314/ajtcam.v6i1.57071

Moghadamtousi SZ, Fadaeinasab M, Nikzad S, Mohan G, Ali HM, Kadir HA. Annona muricata (Annonaceae): A Review of Its Traditional Uses, Isolated Acetogenins and Biological Activities. International journal of molecular sciences. 2015; 16(7),:15625–15658. doi.org/10.3390/ijms160715625 . DOI: https://doi.org/10.3390/ijms160715625

CCAC GUIDELINES .The Canadian Veterinary Journal , 2003; 44(8):631.

Agu KC, Okolie NP, Eze I, Anionye JC , Falodun A. Phytochemical analysis, toxicity profile, and hemomodulatory properties of Annona muricata (Soursop).The Egyptian Journal of Haematology. 2017; 42(1):36-44. DOI: https://doi.org/10.4103/1110-1067.206431

Schmidt W. The micronucleus test for cytogenetic analysis. In Hollaender, (ed.), Chemical Mutagens, Vol. 4. Plenum Press, New York, 1976; 31–53 DOI: https://doi.org/10.1007/978-1-4684-0892-8_2

Alabi OA , Bakare AA. . Genotoxicity and mutagenicity of electronic waste leachates using animal bioassays. Tox Env Chem.2011; 93(5): 1073–1088. DOI: https://doi.org/10.1080/02772248.2011.561949

Oyeyemi IT, Yekeen OM, Odusina PO, Ologun TM, et al., Genotoxicity and antigenotoxicity study of aqueous and hydro-methanol extracts of Spondias mombin L., Nymphaea lotus L. and Luffa cylindrical L. using animal bioassays. Interdiscip Toxicol. 2015 ;8(4):184-92 DOI: https://doi.org/10.1515/intox-2015-0028

Onuah CL, Chukwuma CC, Ohanador R, Chukwu CN, Iruolagbe J. Quantitative Phytochemical Analysis of Annona muricata and Artocarpus heterophyllus Leaves Using Gas Chromatography-flame Ionization Detector. Trends in Applied Sciences Research, 2019; 14: 113-118. DOI: https://doi.org/10.3923/tasr.2019.113.118

Hasmila I, Natsir H, Soekamto NH. Phytochemical analysis and antioxidant activity of soursop leaf extract (Annona muricata Linn.) J. Phys.: Conf. Ser. 2019; 1341(3): 20-27. DOI: https://doi.org/10.1088/1742-6596/1341/3/032027

Roduan, M R, Hamid R A, Sulaiman H, Mohtarrudin N. Annona muricata leaves extracts prevent DMBA/TPA-induced skin tumorigenesis via modulating antioxidants enzymes system in ICR mice. Biomed. Pharmacother. 2017; 94: 481–488.doi: 10.1016/j.biopha.2017. 07.133 DOI: https://doi.org/10.1016/j.biopha.2017.07.133

Abdulwahab SM.,Jantan J.,Hanque MA.,Arsha L. . Exploring the Leaves of Annona muricata L. as a Source of Potential Anti-inflammatory and Anticancer Agents. Front. Pharmacol . 2018; 9: 661.

Jacobo- Hernier N, Perez-Plasencia C, Castro-Torres VA, Martinez-Vazquez, Gonzalez-Esquinca AR, and Zentella-Dehesa A. Selective Acetogenins and their potential as anticancer agents. Frontiers in Pharmacology. 2019; 10:783.PMID:31379567. DOI: https://doi.org/10.3389/fphar.2019.00783

Syed Najmuddin SU, Romli MF, Hamid M, Alitheen NB, Nik Abd Rahman NM. Anti-cancer effect of Annona Muricata Linn Leaves Crude Extract (AMCE) on breast cancer cell line. BMC Complement Altern Med. 2016 ; 16(1):311. doi: 10.1186/s12906-016-1290-y. DOI: https://doi.org/10.1186/s12906-016-1290-y

Alali FQ, Liu XX, McLaughlin JL. Annonaceous acetogenins: recent progress. J Nat Prod. 1999; 62(3):504–40. DOI: https://doi.org/10.1021/np980406d

McLaughlin JL. Paw paw and cancer: annonaceous acetogenins from discovery to commercial products. J Nat Prod. 2008; 71(7):1311–1321. DOI: https://doi.org/10.1021/np800191t

Millimouno FM, Dong J, Yang L, Li J, Li X. Targeting apoptosis pathways in cancer and perspectives with natural compounds from mother nature. Cancer Prev. Res. 2014; 7:1081–1107. doi: 10.1158/1940-6207.CAPR-14-0136. DOI: https://doi.org/10.1158/1940-6207.CAPR-14-0136

Habli Z., Toumieh G, Fatfat M, Rahal ON, Gali-Muhtasib H . Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms. Molecules (Basel, Switzerland).2017; 22(2): 250. doi.org/10.3390/molecules22020250 . DOI: https://doi.org/10.3390/molecules22020250

Gyesi JN, Opoku R, Borquaye LS. Chemical Composition, Total Phenolic Content, and Antioxidant Activities of the Essential Oils of the Leaves and Fruit Pulp of Annona muricata L. (Soursop) from Ghana. Biochem Res Int. 2019; 4164576. doi: 10.1155/2019/4164576. DOI: https://doi.org/10.1155/2019/4164576

Abdul Wahab SM, Jantan I, Haque Md. A, Arshad L. Exploring the Leaves of Annona muricata L. as a Source of Potential Anti-inflammatory and Anticancer Agents. Frontiers in Pharmacology.2018:9; 661. DOI: https://doi.org/10.3389/fphar.2018.00661

Ménan, H, Banzouzi, JT, Hocquette, A, Pélissier, Y, Blache, Y, Koné, M. et al. Antiplasmodial activity and cytotoxicity of plants used in West African traditional medicine for the treatment of malaria. J. Ethnopharmacol. 2016; 105: 131–136. doi: 10.1016/j.jep.2005.10.027. DOI: https://doi.org/10.1016/j.jep.2005.10.027

Osorio E, Arango GJ, Jiménez N, Alzate F, Ruiz G, Gutiérrez D, et al. Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae. J. Ethnopharmacol. 2007; 111: 630–635. doi: 10.1016/j.jep.2007.01.015. DOI: https://doi.org/10.1016/j.jep.2007.01.015

George VC., Kumar D, Rajkumar V, Suresh P, and Kumar R A. Quantitative assessment of the relative antineoplastic potential of the n-butanolic leaf extract of Annona muricata Linn. in normal and immortalized human cell lines. Asian Pac. J. Cancer Prev. 2012: 13: 699–704. doi: 10.7314/APJCP.2012.13.2.699. DOI: https://doi.org/10.7314/APJCP.2012.13.2.699

Torres MP, Rachagani S, Purohit V, Pandey P, Joshi S, Moore E D, et al. Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer letter. 2012: 323: 29–40. doi: 10.1016/j.canlet.2012.03.031. DOI: https://doi.org/10.1016/j.canlet.2012.03.031

Elizabeth OO, Nonso IF, Adebola NI, John OJ. Comparative Study on Chemical Composition and Antioxidant Activity of Annona muricata Plant Parts Cultivated in Covenant University, Ota, Ogun State, Nigeria. Curr Res Nutr Food Sci. 2018; 6(3): 807-815. doi.org/10.12944/CRNFSJ.6.3.23. DOI: https://doi.org/10.12944/CRNFSJ.6.3.23