Aqueous extract from Chrysophyllum cainito bark exhibits embryonic toxicity in Danio rerio and negligible acute toxicity in adult Wistar rats

Authors

  • Hau Van Doan 1. School of Preclinical Sciences, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, Thailand; 2. Department of Pharmacy, School of Medicine and Pharmacy, Tra Vinh University, Tra Vinh, Vietnam
  • Pishyaporn Sritangos School of Preclinical Sciences, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, Thailand
  • Oratai Weeranantanapan School of Preclinical Sciences, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, Thailand
  • Nuannoi Chudapongse School of Preclinical Sciences, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, Thailand

DOI:

https://doi.org/10.2298/ABS211110046D

Keywords:

acute toxicity, zebrafish, Wistar rat, embryotoxicity, Chrysophyllum cainito

Abstract

Paper description:

  • Chrysophyllum cainito is a widely used alternative antidiabetic medicine in many countries in Asia, and previous studies showed that C. cainito bark extract exerts antidiabetic, anti-inflammatory, proapoptotic and anticancer effects.
  • Due to lack of toxicity assessment, acute toxicity of the aqueous C. cainito bark extract in the rat, and embryotoxicity in the zebrafish experimental model were examined.
  • First evidence that the bark extract induces embryotoxicity in zebrafish at low concentrations and negligible acute toxicity in adult Wistar rats is provided.
  • C. cainito bark extract should be cautiously applied in women during pregnancy.

Abstract: Chrysophyllum cainito has been used as a traditional medicine to treat a wide range of diseases, but the toxicity profile of this plant remains unknown. This study aimed to evaluate the acute toxicity of the aqueous extract of C. cainito (CE) bark based on OECD guidelines in two different in vivo experimental models: acute single-dose oral toxicity in adult Wistar rats and the zebrafish embryo acute toxicity test. All concentrations of CE (500-4000 mg/kg) tested during a 14-day period in both male and female rats showed no effect on behavior, body weight, organ weights, biochemical and hematological parameters. In contrast, CE significantly delayed zebrafish embryo hatching and decreased embryo survival rates in a dose-dependent manner. Hatched larvae were notably sensitive to CE-induced toxicity compared to unhatched fish embryos. Acridine orange staining showed that CE induced apoptosis in the yolk sac region that is responsible for supplying nutrients to support larval growth and development. According to OECD guidelines, CE was identified as GHS category 5, a substance with low to no acute toxicity. However, as embryotoxicity was observed in zebrafish, CE use during pregnancy should be exercised with caution until further examination of its safety.

Downloads

Download data is not yet available.

References

The World Health Organization. WHO Traditional Medicine Strategy 2014 - 2023. Geneva: WHO. 2021-[cited 2021 Jan 26]. Available from: https://www.who.int/publications/i/item/9789241506096

Neergheen-Bhujun VS. Underestimating the toxicological challenges associated with the use of herbal medicinal products in developing countries. Biomed Res Int. 2013;2013:804086.

https://doi.org/10.1155/2013/804086

Sofowora A, Ogunbodede E, Onayade A. The role and place of medicinal plants in the strategies for disease prevention. Afr J Tradit Complement Altern Med. 2013;10(5):210-29.

https://doi.org/10.4314/ajtcam.v10i5.2

Tamilselvan N, Thirumalai T, Shyamala P, David E. A review on some poisonous plants and their medicinal values. J Acute Dis. 2014;3(2):85-9.

https://doi.org/10.1016/S2221-6189(14)60022-6

Bussmann RW, Malca G, Glenn A, Sharon D, Nilsen B, Parris B, Dubose D, Ruiz D, Saleda J, Martinez M, Carillo L, Walker K, Kuhlman A, Townesmith A. Toxicity of medicinal plants used in traditional medicine in Northern Peru. J Ethnopharmacol. 2011;137(1):121-40.

https://doi.org/10.1016/j.jep.2011.04.071

Woo CSJ, Lau JSH, El-Nezami H. Herbal medicine: Toxicity and recent trends in assessing their potential toxic effects. Adv. Bot. Res. 2012;62:365-84.

https://doi.org/10.1016/B978-0-12-394591-4.00009-X

Fennell CW, Lindsey KL, McGaw LJ, Sparg SG, Stafford GI, Elgorashi EE, Grace OM, Staden JV. Assessing African medicinal plants for efficacy and safety: pharmacological screening and toxicology. J Ethnopharmacol. 2004;94(2-3):205-17.

https://doi.org/10.1016/j.jep.2004.05.012

World Health Organization. WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems. Geneva: World Health Organization; 2004.

Ekor M. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front Neurol. 2014;4:1-10.

https://doi.org/10.3389/fphar.2013.00177

Doan HV, Le TP. Chrysophyllum cainito: a tropical fruit with multiple health benefits. Evid Based Complement Alternat Med. 2020;2020:7259267.

https://doi.org/10.1155/2020/7259267

Koffi Ng, Ernest AK, Marie-Solange T, Beugré K, Noël ZG. Effect of aqueous extract of Chrysophyllum cainito leaves on the glycaemia of diabetic rabbits. Afr J Pharm Pharmacol. 2009;3(10):501-6.

Doan HV, Riyajan S, Iyara R, Chudapongse N. Antidiabetic activity, glucose uptake stimulation and α-glucosidase inhibitory effect of Chrysophyllum cainito L. stem bark extract. BMC Complement Altern Med. 2018;18(1):267.

https://doi.org/10.1186/s12906-018-2328-0

Moreira DdL, Teixeira SS, Monteiro MHD, De-Oliveira ACAX, Paumgartten FJR. Traditional use and safety of herbal medicines. Rev Bras Farmacogn. 2014;24:248-57.

https://doi.org/10.1016/j.bjp.2014.03.006

Nasri H, Shirzad H. Toxicity and safety of medicinal plants. J Herbmed Pharmacol. 2013;2:21-2.

Strähle U, Scholz S, Geisler R, Greiner P, Hollert H, Rastegar S, Schumacher A, Selderslaghs I, Weiss C, Witters H, Braunbeck T. Zebrafish embryos as an alternative to animal experiments-A commentary on the definition of the onset of protected life stages in animal welfare regulations. Reprod Toxicol. 2012;33(2):128-32.

https://doi.org/10.1016/j.reprotox.2011.06.121

The Office of Laboratory Animal Welfare. 21st century cures act - Animal care and use in research. Maryland: National Institutes of Health. 2021-[cited 2021 Oct 26]. Available from: https://olaw.nih.gov/policies-laws/21st-century-cures-act/Zebrafish#policies

Lopez-Luna J, Al-Jubouri Q, Al-Nuaimy W, Sneddon LU. Impact of analgesic drugs on the behavioural responses of larval zebrafish to potentially noxious temperatures. Appl Anim Behav Sci. 2017;188:97-105.

https://doi.org/10.1016/j.applanim.2017.01.002

Lopez-Luna J, Al-Jubouri Q, Al-Nuaimy W, Sneddon LU. Impact of stress, fear and anxiety on the nociceptive responses of larval zebrafish. PLoS One. 2017;12(8):e0181010-e.

https://doi.org/10.1371/journal.pone.0181010

Malafoglia V, Colasanti M, Raffaeli W, Balciunas D, Giordano A, Bellipanni G. Extreme thermal noxious stimuli induce pain responses in zebrafish larvae. J Cell Physiol. 2014;229(3):300-8.

https://doi.org/10.1002/jcp.24447

The Organisation for Economic Co-operation and Development. Test No. 423: Acute oral toxicity - Acute toxic class method. OECD Guidelines for the testing of chemicals. Section 4. Paris: OECD Publishing. 2002.

Charan J, Kantharia ND. How to calculate sample size in animal studies? J Pharmacol. Pharmacother. 2013;4:303-6.

https://doi.org/10.4103/0976-500X.119726

The Organisation for Economic Co-operation and Development. Test No. 236: Fish embryo acute toxicity (FET) test. OECD Guidelines for the testing of chemicals, Section 2. Paris: OECD Publishing. 2013.

Hermsen SAB, van den Brandhof E-J, van der Ven LTM, Piersma AH. Relative embryotoxicity of two classes of chemicals in a modified zebrafish embryotoxicity test and comparison with their in vivo potencies. Toxicol In Vitro. 2011;25:745-53.

https://doi.org/10.1016/j.tiv.2011.01.005

Wallace CK, Bright LA, Marx JO, Andersen RP, Mullins MC, Carty AJ. Effectiveness of rapid cooling as a method of euthanasia for young zebrafish (Danio rerio). J Am Assoc Lab Anim Sci. 2018;57(1):58-63.

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676-82.

https://doi.org/10.1038/nmeth.2019

Mukinda JT, Eagles PFK. Acute and sub-chronic oral toxicity profiles of the aqueous extract of Polygala fruticosa in female mice and rats. J Ethnopharmacol. 2010;128:236-40.

https://doi.org/10.1016/j.jep.2010.01.022

Yuet Ping K, Darah I, Chen Y, Sreeramanan S, Sasidharan S. Acute and subchronic toxicity study of Euphorbia hirta L. methanol extract in rats. Biomed Res Int. 2013;2013:182064.

https://doi.org/10.1155/2013/182064

Silva MG, Aragão TP, Vasconcelos CF, Ferreira PA, Andrade BA, Costa IM, Costa-Silva JH, Wanderley AG, Lafayette SS. Acute and subacute toxicity of Cassia occidentalis L. stem and leaf in Wistar rats. J Ethnopharmacol. 2011;136(2):341-6.

https://doi.org/10.1016/j.jep.2011.04.070

Parasuraman S. Toxicological screening. J Pharmacol Pharmacother. 2011;2(2):74-9.

https://doi.org/10.4103/0976-500X.81895

Keegan TE, Simmons JE, Pegram RA. NOAEL and LOAEL determinations of acute hepatotoxicity for chloroform and bromodichloromethane delivered in an aqueous vehicle to F344 RATS. J Toxicol Environ Health, A. 1998;55(1):65-75.

https://doi.org/10.1080/009841098158629

Denny KH, Stewart CW. Chapter 5 - Acute, sub-acute, sub-chronic and chronic general toxicity testing for preclinical drug development. In: Faqi AS, editor. A comprehensive guide to toxicology in preclinical drug development (Second edition). Cambridge: Academic Press; 2013. p. 87-105.

https://doi.org/10.1016/B978-0-12-387815-1.00005-8

Sahi J, Grepper S, Smith C. Hepatocytes as a tool in drug metabolism, transport and safety evaluations in drug discovery. Curr Drug Disc Technol. 2010;7:188-98.

https://doi.org/10.2174/157016310793180576

Lohr JW, Willsky GR, Acara MA. Renal drug metabolism. Pharmacol Rev. 1998;50:107 -42.

National Research Council. A framework to guide selection of chemical alternatives. Washington, DC: The National Academies Press; 2014. 280 p.

Doan HV, Sritangos P, Iyara R, Chudapongse N. Chrysophyllum cainito stem bark extract induces apoptosis in Human hepatocarcinoma HepG2 cells through ROS-mediated mitochondrial pathway. PeerJ. 2020;8:e10168.

https://doi.org/10.7717/peerj.10168

Hill AJ, Teraoka H, Heideman W, Peterson RE. Zebrafish as a model vertebrate for investigating chemical toxicity. Toxicol Sci. 2005;86(1):6-19.

https://doi.org/10.1093/toxsci/kfi110

Mandrell D, Truong L, Jephson C, Sarker MR, Moore A, Lang C, Simonich MT, Tanguay RL. Automated zebrafish chorion removal and single embryo placement: optimizing throughput of zebrafish developmental toxicity screens. J Lab Autom. 2012;17:66-74.

https://doi.org/10.1177/2211068211432197

Li J, Zhang Y, Liu K, He Q, Sun C, Han J, Han L, Tian Q. Xiaoaiping induces developmental toxicity in zebrafish embryos through activation of ER stress, apoptosis and the Wnt pathway. Front Pharmacol. 2018;9:1250.

https://doi.org/10.3389/fphar.2018.01250

Muller EB, Lin S, Nisbet RM. Quantitative adverse outcome pathway analysis of hatching in zebrafish with CuO nanoparticles. Environ Sci Technol. 2015;49:11817-24.

https://doi.org/10.1021/acs.est.5b01837

Trikić MZ, Monk P, Roehl H, Partridge LJ. Regulation of zebrafish hatching by Tetraspanin cd63. PLoS One. 2011;6(5):e19683.

https://doi.org/10.1371/journal.pone.0019683

Johnson A, Carew E, Sloman KA. The effects of copper on the morphological and functional development of zebrafish embryos. Aquat Toxicol. 2007;84:431-8.

https://doi.org/10.1016/j.aquatox.2007.07.003

Fraher D, Sanigorski A, Mellett Natalie A, Meikle Peter J, Sinclair Andrew J, Gibert Y. Zebrafish embryonic lipidomic analysis reveals that the yolk cell is metabolically active in processing lipid. Cell Reports. 2016;14(6):1317-29.

https://doi.org/10.1016/j.celrep.2016.01.016

Sant KE, Timme-Laragy AR. Zebrafish as a model for toxicological perturbation of yolk and nutrition in the early embryo. Curr Environ Health Rep. 2018;5(1):125-33.

https://doi.org/10.1007/s40572-018-0183-2

Ulhaq M, Sundström M, Larsson P, Gabrielsson J, Bergman Å, Norrgren L, Örn S. Tissue uptake, distribution and elimination of 14C-PFOA in zebrafish (Danio rerio). Aquat Toxicol. 2015;163:148-57.

https://doi.org/10.1016/j.aquatox.2015.04.003

Choudhury S, Thomas JK, Sylvain NJ, Ponomarenko O, Gordon RA, Heald SM, Janz DM, Krone PH, Coulthard I, George GN, Pickering IJ. Selenium preferentially accumulates in the eye lens following embryonic exposure: a confocal X-ray fluorescence imaging study. Environ Sci Technol. 2015;49(4):2255-61.

https://doi.org/10.1021/es503848s

Downloads

Published

2021-12-15

How to Cite

1.
Doan HV, Sritangos P, Weeranantanapan O, Chudapongse N. Aqueous extract from Chrysophyllum cainito bark exhibits embryonic toxicity in Danio rerio and negligible acute toxicity in adult Wistar rats. Arch Biol Sci [Internet]. 2021Dec.15 [cited 2022Sep.28];73(4):523-3. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/7224

Issue

Section

Articles

Most read articles by the same author(s)