Toxicological Safety Evaluation of Ethanol Extract of Artocarpus altilis Leaves in Wistar Rats (Rattus norvegicus)
doi.org/10.26538/tjnpr/v5i11.7
Keywords:
Acute toxicity, Artocarpus altilis, Ethanol extract, Female rats, ToxicologyAbstract
Safety testing of toxicological properties of a drug could be obtained from preclinical trials using test animals as models designed for a series of toxicity tests. This study was aimed at evaluating the acute toxicity of the ethanol extract of Artocarpus altilis leaves in rats. Ethanol extract was prepared from the leaves of A. altilis. Twenty rats were randomly divided into four groups of five rats per group: one control group and three treatment groups that were given oral administration of 500, 2,000, and 5,000 mg/kg body weight (BW), respectively of ethanol leaf extract of A. altilis. The animals’ general toxicological behavior and mortality were observed every 24 hours. The rats were sacrificed on the 15th day and the body weight, relative organ weight, biochemical parameters, and histopathology of the vital organs were analyzed. The results indicated that the extract did not affect the body and relative organ weights of the rats. Conversely, the biochemical parameters showed that alanine aminotransferase (ALT) and creatinine increased in the 5,000 mg/kg treatment group. Meanwhile, there was no significant difference (P>0.05) in aspartate transaminase (AST) and urea. In addition, the lethal dose (LD50) of the extract was higher than 5,000 mg/kg BW. There was no evidence of toxicity in the rats after acute exposure to the ethanol extract of A. altilis leaves. The findings of this study reveal that oral administration of the ethanol extract of A. altilis leaves is considered safe and is not associated with any distinct toxicity or side effects.
References
Ozawa S, Higgins CR, Yemeke TT, Nwokike JI, Evans L, Hajjou M, Pribluda VS. Importance of medicine quality in achieving universal health coverage. PLoS One. 2020;15(7):e0232966.
Medetkhanov FA, Muravyova KV, Khadeev DP, Konakova IA, Yarullina ES. Comparative assessment of the parameters of acute toxicity of natural products. BIO Web Conf. 2020; 17(00146):1-5.
Erhirhie EO, Ihekwereme CP, Ilodigwe EE. Advances in acute toxicity testing: Strengths, weaknesses and regulatory acceptance. Interdiscip Toxicol. 2018; 11(1):5-12.
Wang Y, Xu K, Lin L, Pan Y, Zheng X. Geranyl flavonoids from the leaves of Artocarpus altilis. Phytochem. 2007; 68(9):1300-1306.
Akinwumi IA and Sonibare MA. Use of medicinal plants for the treatment of gastric ulcer in some parts of Southwestern Nigeria. Afr J Pharm Pharmacol. 2019; 13(15):223-235.
Shamaun SS, Rahmani M, Hashim NM, Ismail HBM, Sukari MA, Lian GEC, Go R. Prenylated flavones from Artocarpus altilis. J Nat Med. 2010; 64(4):478-481.
Wang Y, Deng T, Lin L, Pan Y, Zheng X. Bioassay-guided isolation of antiatherosclerotic phytochemicals from Artocarpus altilis. Phyther Res. 2006; 20(12):1052-1055.
Maleki SJ, Crespo JF, Cabanillas B. Anti-inflammatory effects of flavonoids. Food Chem. 2019; 299(125124):1-11.
Wang Z, Liu J, Yang Y, Zhu H. A Review: The Antiinflammatory, Anticancer and Antibacterial Properties of Four Kinds of Licorice Flavonoids Isolated from Licorice. Curr Med Chem. 2018; 7(12):1997-2011.
DeSales IRP, Formiga RDO, Machado FDF, Nascimento RF, Pessoa MMB, Barros MEFX, Vieira GC, Gadelha FAAF, Marinho AF, Filho JMB, Junior RFDA, Antunes AA, Batista LM. Cytoprotective, antioxidant and antiinflammatory mechanism related to antiulcer activity of Cissampelos sympodialis Eichl. in animal models. J Ethnopharmacol. 2018; 222(8):190-200.
Sharma M, Yadav S, Ganesh N, Srivastava MM, Srivastava S. Biofabrication and characterization of flavonoid-loaded Ag, Au, Au–Ag bimetallic nanoparticles using seed extract of the plant Madhuca longifolia for the enhancement in wound healing bio-efficacy. Prog Biomater. 2019; 8(1):51-63.
OECD. OECD Guideline for Testing of Chemicals: Acute Oral Toxicity – Fixed Dose Procedure No. 420. Section 4. Paris: OECD Publishing; 2002; 1-14p.
Timchalk C, Nolan RJ, Mendrala AL, Dittenber DA, Brzak KA, Mattsson JL. A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for the organophosphate insecticide chlorpyrifos in rats and humans. Toxicol Sci. 2002; 66(1):34-53.
Kobuchi S, Katsuyama Y, Ito Y. Mechanism-based pharmacokinetic–pharmacodynamic (PK–PD) modeling and
simulation of oxaliplatin for hematological toxicity in rats. Xenobiotica. 2020;50(2):223-230.
Hwang JH, Ku J, Jung C. Evaluation of the Single-Dose Toxicity of Capsaicin Pharmacopuncture in Rats. J Acupunct Res. 2020; 7(3):167-172.
Hao Y, Sun G, Fan T, Tang X, Zhang J, Liu Y, Zhang N, Zhao L, Zhong R, Peng Y. In vivo toxicity of nitroaromatic compounds to rats: QSTR modelling and interspecies toxicity relationship with mouse. J Hazard Mater. 2020; 399:122981.
Lala V, Goyal A, Bansal P, Minter DA. Liver Function Tests. StatPearls Publishing; 2020. Accessed September 18, 2020. https://www.ncbi.nlm.nih.gov/books/NBK482489/
Lonardo A, Leoni S, Alswat KA, Fouad Y. History of Nonalcoholic Fatty Liver Disease. Int J Mol Sci. 2020; 21(16):5888.
Joshi M. Cancer Chemotherapy And Hepatotoxicity: An Update.; 2014. Accessed September 18, 2020. www.iajpr.com Indo Am J Pharm Res. 2014; 4(06):2976-2984.
Oh RC, Hustead TR, Ali SM, Pantsari MW. Mildly Elevated Liver Transaminase Levels: Causes and Evaluation. American Family Physician. 2017; 96(11):711-715.
Aba PE, Ihedioha JI, Nwaogu IC. Sensitivities, specificities and correlates of certain liver damage marker parameters in Red Sokoto goats. Comp Clin Path. 2020; 29(5):1061-1068.
Soliman AM, Rizk HA, Shalaby MA, Elkomy AA. Mechanisms of Hepato-Renal Protective Activity of Ocimum basilicum Leaf Extract against Paracetamol Toxicity in Rat Model. Adv Anim Vet Sci. 2020; 8(4):385-391.
El-Bakry KA, Deef LEM, Habbak LZ, El-Naeli SS. Hepatorenal Toxicity of Patulin and its Modulation by Ginger
(Zingiber officinale) in Rats. Pak J Zool. 2020; 52(2):679-
Lee HY, Nam Y, Choi WS, Kim TW, Lee J, Sohn UD. The hepato-protective effect of eupatilin on an alcoholic liver disease model of rats. Korean J Physiol Pharmacol. 2020;24(5):385-394.
Joliat GR, Labgaa I, Demartines N, Halkic N. Acute kidney injury after liver surgery: does postoperative urine output correlate with postoperative serum creatinine? Hepato-Pancreato-Biliary. 2020; 22(1):144-150.
Laddha AP and Kulkarni YA. Daidzein Attenuates Kidney Damage in Diabetic Rats. The FASEB J. 2020; 34(S1):1.
Scotcher D, Arya V, Yang X, Zhao P, Zhang L, Huang SM, Rostami-Hodjegan A, Galetin A. A Novel Physiologically Based Model of Creatinine Renal Disposition to Integrate Current Knowledge of Systems Parameters and Clinical Observations. CPT Pharmacomet
Syst Pharmacol. 2020; 9(6):310-321.
Ok F, Erdogan O, Durmus E, Carkci S, Canik A. Predictive values of blood urea nitrogen/creatinine ratio and other routine blood parameters on disease severity and survival of COVID‐19 patients. J Med Virol. 2021; 93(2):786-793.
Neghab M, Amiri F, Soleimani E, Yousefinejad S, Hassanzadeh J. Toxic responses of the liver and kidneys following occupational exposure to anesthetic gases. EXCLI J. 2020; 19(11):418-429.
Denise MI, Carla BM, Ana JP, Fabiana SF, Fernanda CS, Ana MI. Evaluation of the toxic effects of the bottled medicine (garrafada) containing the Echinacea purpurea, Annona muricata, Tabebuia avellanedae, Pterodon emarginatus and Uncaria tomentosa in rats. Med Plants Res. 2020; 14(3):105-117.
Da Silva Xavier G. The Cells of the Islets of Langerhans. J Clin Med. 2018; 7(3):54.
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
