Toxicology International (Formerly Indian Journal of Toxicology)

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Toxicological Assessment of Methanolic Fruit Extract of Zanthoxylum Acanthopodium Dc. In Swiss Albino Mice: Acute and Sub-acute Toxicity Study


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1 Department of Zoology, North-Eastern Hill University, Shillong – 793022, Meghalaya,, India
     

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Zanthoxylum acanthopodium DC. is widely used in traditional plant-based medical practices in India, with different parts of this plant used to treat a variety of ailments. Though this has been a time-tested practice, the side effects and other implications that the plant may have should not be overlooked. This study evaluated the toxicity of the methanolic fruit extract of Z. acanthopodium in Swiss albino mice by conducting acute and sub-acute toxicity tests using hematological, biochemical, ultrastructural analysis, sperm abnormality, and genotoxicity as parameters. For the acute toxicity test, mice were treated with a single dose of 5000 mg extract/kg bw of mice. While for sub-acute toxicity test, doses of 200, 500, and 1000 mg of the extract/kg bw were administered to the mice. Furthermore, a satellite group of the respective control group and the highest dose group were employed to observe the post-treatment effect that the plant may have. The acute toxicity test resulted in a significant reduction of the mean body weight gain in treated mice, but, no signs of morbidity and mortality were recorded. Sub-acute toxicity test revealed a negative effect of the plant extract on the blood and biochemical parameters. Light and electron microscopic examination of the liver and kidney showed the damaging effects of the extract on the tissues and the cellular structures. In addition, the extract induced sperm abnormalities with a significant reduction of sperm count and sperm viability, and caused an increase in the percentage of abnormally shaped sperms. The extract treatment also resulted in an increased frequency of chromosomal aberrations as well as cell death.

Keywords

Apoptosis, Biochemistry, Chromosomal Aberrations, Hematology, Sperm Abnormality, Ultrastructure, Zanthoxylum acanthopodium.
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  • Rates SMK. Plants as source of drugs. Toxicon. 2001; 39(5):603–13. https://doi.org/10.1016/S0041-0101(00)00154-9

  • World Health Organisation. WHO traditional medicine strategy: 2014–2023. Geneva: World Health Organisation; 2013.

  • Karimi A, Majlesi M, Rafieian-Kopaei M. Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol. 2015; 4(1):27–30.

  • Consolini AE, Ragone MI. Patterns of self-medication with medicinal plants and related adverse events - A South American survey. Curr Drug Saf. 2010; 5(4):333–41. https://doi.org/10.2174/157488610792246019. PMid:20615178

  • Wang Y, Han T, Xue LM, Han P, Zhang QY, Huang BK, et al. Hepatotoxicity of kaurene glycosides from Xanthium strumarium L. fruits in mice. Pharmazie. 2011; 66(6):445–9.

  • Akinpelu BA, Oyedapo OO, Iwalewa EO, Shode F. Biochemical and histopathological profile of toxicity induced by saponin fraction of Erythrophleum suaveolens (Guill. and Perri.) bark. Phytopharmacol. 2012; 3(1):38–53.

  • Neuman MG, Cohen L, Opris M, Nanau RM, Hyunjin J. Hepatotoxicity of pyrrolizidine alkaloids. J Pharm Pharm Sci. 2015; 18(4):825–43. https://doi.org/10.18433/J3BG7J. PMid:26626258

  • Sharma HK, Zaman MK. The marvel plant of Meghalaya: Zanthoxylum acanthopodium DC. Germany: LAP Lambert Academic Publishing; 2016.

  • Hanum IT, Laila L. Evaluation of anti-aging and anti-acne effect of Andaliman (Zanthoxylum acanthopodium DC.) ethanolic extract peel off gel mask. Asian J Pharm Clin Res. 2018; 11(13):90–3. https://doi.org/10.22159/ajpcr.2018.v11s1.26576

  • Bhatt V, Kumar N, Sharma U, Singh B. Comprehensive metabolic profiling of Zanthoxylum armatum and Zanthoxylum acanthopodium leaves, bark, flowers and fruits using ultra high performance liquid chromatography. Sep Sci Plus. 2018; 1(5):311–24. https://doi.org/10.1002/sscp.201800004

  • Yanti Y, Gea BP, Lay BW. Antihalitosis effect of essential oil extracted from Zanthoxylum acanthopodium fruits. J Teknol. 2019; 81(5):91–6. https://doi.org/10.11113/jt.v81.13655

  • Gupta DD, Mandi SS. Species specific AFLP markers for authentication of Zanthoxylum acanthopodium and Zanthoxylumo xyphyllum. J Med Plants Stud. 2013; 1(6):1–9.

  • Medhi K, Deka M, Bhau BS. The genus Zanthoxylum - A stockpile of biological and ethnomedicinal properties. Sci Rep. 2013; 2:697–704. https://doi.org/10.1016/j.mgene.2014.09.009. PMid:25606454. PMCid:PMC4287866

  • Muzafri A, Julianti E, Rusmarilin H. The extraction of antimicrobials component of andaliman (Zanthoxylum acanthopodium DC.) and its application on catfish (Pangasius sutchi) fillet. IOP ConfSer: Earth Environ Sci. 2018; 122:012089. https://doi.org/10.1088/1755-1315/122/1/012089

  • Devi OK, Rao KS, Bidalia A. Characterization of chemical constituents in Zanthoxylum acanthopodium DC. leaf using GC-MS. Indo Am J Pharm Res. 2015; 5(5):1690–4.

  • Harahap U, Hasibuan P, Sitorus P, Arfian N, Satria D. Antimigration activity of an ethyl acetate fraction of Zanthoxylum acanthopodium DC. fruits in 4T1 breast cancer cells. Asian Pac J Cancer Prev. 2018; 19(2):565–9.

  • Satria D, Silalahi J, Haro G, Ilyas S, Hasibuan PAZ. Cell cycle inhibition of ethylacetate fraction of Zanthoxylum acanthopodium DC. fruit against T47D cells. Open Access Maced J Med Sci. 2019; 7(5):726–9. https://doi.org/10.3889/oamjms.2019.178. PMid:30962828. PMCid:PMC6447336

  • Hynniewta SR, Kumar Y. Herbal remedies among the Khasi traditional healers and village folks in Meghalaya. Indian J Tradit Know. 2008; 7(4):581–6.

  • Bhattacharya J, Lakshmi AI, Ata S, Sarma OS. Evaluation of cytotoxic activity of Zanthoxylum acanthopodium in Dalton’s lymphoma ascites cells induced cancer in mice. European J Biomed Pharm Sci. 2017; 4(10):541–8.

  • Organization for Economic Cooperation and Development (OECD) guideline 423 for testing of chemicals: Acute oral toxicity - Acute toxic class method. Organization of Economic Cooperation and Development, December, Paris; 2001. p. 1–14. https://doi.org/10.1787/9789264071001-en

  • Organization for Economic Cooperation and Development (OECD) guideline 407 for testing of chemicals: Repeated dose 28-day oral toxicity study in Rodents. Organization for Economic Cooperation and Development, October, Paris; 2008. p. 1–13. https://doi.org/10.1787/9789264070684-en

  • Dey S, Baul TSB, Roy B, Dey D. A new rapid method of air-drying for scanning electron microscopy using tetramethylsilane. Journal Microsc. 1989; 156(2):259–61. https://doi.org/10.1111/j.1365-2818.1989.tb02925.x

  • Roy B, Tandon V. Usefulness of tetramethylsilane in the preparation of helminth parasites for scanning electron microscopy. Riv Parassitol. 1991; 8(12):405–13.

  • World Health Organisation. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organisation; 2010.

  • Preston RJ, Dean BJ, Galloway S, Holden H, McFee AF, Shelby M. Mammalian in vivo cytogenetic assays. Analysis of chromosome aberrations in bone marrow cells. Mutat Res. 1987; 189(2):157–65. https://doi.org/10.1016/0165-1218(87)90021-8

  • Marrelli M, Conforti F, Araniti F, Statti GA. Effects of saponins on lipid metabolism: A review of potential health benefits in the treatment of obesity. Molecules. 2016; 21(10):1404. https://doi.org/10.3390/molecules21101404. PMid:27775618. PMCid:PMC6273086

  • Jambocus N, Ismail A, Khatib A, Mahomoodally F, Saari N, Mumtaz MW, et al. Morinda citrifolia L. leaf extract prevent weight gain in Sprague-Dawley rats fed a high fat diet. Food Nutr Res. 2017; 61(1):1338919. https://doi.org/10.1080/16546628.2017.1338919. PMid:28814950. PMCid:PMC5553101

  • Muriithi NJ, Maina GS, Maina MB, Kiambi MJ, Kelvin JK, Umar A, et al. Determination of haematological effects of methanolic leaf extract of Vernonia lasiopus in normal mice. J Blood Lymph. 2015; 5:139. https://doi.org/10.4172/2165-7831.1000139

  • Arika WM, Nyamai DW, Musila MN, Ngugi MP, Njagi ENM. Hematological markers of in vivo toxicity. J Hematol Thrombo Dis. 2016; 4:236. https://doi.org/10.4172/2329-8790.1000236

  • D’Alessandro A, Dzieciatkowska M, Nemkov T, Hansen KC. Red blood cell proteomics update: Is there more to discover? Blood Transfus. 2017; 15(2):182–7.

  • Stock W, Hoffman R. White blood cells 1: non-malignant disorders. Lancet. 2000; 355(9212):1351–7. https://doi.org/10.1016/S0140-6736(00)02125-5

  • Wang J. Neutrophils in tissue injury and repair. Cell Tissue Res. 2018; 371(3):531–9. https://doi.org/10.1007/s00441-017-2785-7. PMid:29383445. PMCid:PMC5820392

  • Casotti V, D’Antiga L. Basic principles of liver physiology. In: D’Antiga L, editor. Pediatric hepatology and liver transplantation. Switzerland: Springer, Cham; 2019. https://doi.org/10.1007/978-3-319-96400-3_2

  • Soren AD, Yadav AK, Dhar ED. Toxological evaluation of Cyperus compressus Linn., a traditionally used anthelmintic plant in India. Adv Tradit Med. 2020; 20:367–72. https://doi.org/10.1007/s13596-019-00413-w

  • Kang K, Lee HJ, Yoo JH, Jho EH, Kim CY, Kim M, et al. Cell and nuclear enlargement of SW480 cells induced by a plant lignan, Arctigenin: Evaluation of cellular DNA content using fluorescence microscopy and flow cytometry. DNA Cell Biol. 2011; 30(8):623–9. https://doi.org/10.1089/dna.2010.1199. PMid:21663531

  • Kolios G, Valatas V, Kouroumalis E. Role of Kupffer cells in the pathogenesis of liver disease. World J Gastroenterol. 2006; 12(46):7413–20. https://doi.org/10.3748/wjg.v12.i46.7413. PMid:17167827. PMCid:PMC4087584

  • Safer AM, Afzal M, Hanafy N, Mousa S. Green tea extract therapy diminishes hepatic fibrosis mediated by dual exposure to carbon tetrachloride and ethanol: A histo pathological study. ExpTher Med. 2015; 9(3):787–94. https://doi.org/10.3892/etm.2014.2158. PMid:25667629. PMCid:PMC4316931

  • Darling JR, Sharpe PC, Stiby EK, McAteer JA, Archbold GP, Milligan KR. Serum mitochondrial aspartate transaminase activity after isoflurane or halothane anaesthesia. Br J Anaesth. 2000; 85(2):195–8. https://doi.org/10.1093/bja/85.2.195. PMid:10992823

  • Kim WR, Flamm SL, Di Bisceglie AM, Bodenheimer HC. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology. 2008; 47(4):1363–70. https://doi.org/10.1002/hep.22109. PMid:18366115

  • Lowe D, John S. Alkaline phosphatase. StatPearls [Internet]. [cited on 2020 Jul 3]. Treasure Island (FL): StatPearls Publishing; 2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459201/

  • Ogobuiro I, Tuma F. Physiology, renal. In: StatPearls [Internet]. [cited on 2020 Jul 3]. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538339/

  • Giri BR, Roy B. Nephrotoxic potential of Carex baccans (Family: Cyperaceae): A light and electron microscopic studies. J Toxicol Health, 2013; 103:244–51.

  • Kamran M, Khan MR, Khan HU, Abbas M, Iqbal M, Nazir A. Phytochemical and cytotoxic evaluation of Medicago monantha: In vivo protective potential in rats. Biomed Pharmacother. 2018; 102:1052–63. https://doi.org/10.1016/j.biopha.2018.03.160. PMid:29710522

  • Brandao-Costa RMP, Batistaa JMS, Nascimento TP, Porto ALF. Renal function effects of FDS, a saponin isolated from Filicium decipiens seeds: Biochemical and histopathological studies. J Plant Sci Phytopathol. 2019; 3:107–10. https://doi.org/10.29328/journal.jpsp.1001040

  • Schou KB, Schneider L, Christensen ST, Hoffmann EK. Early-stage apoptosis is associated with DNA-damage-independent ATM phosphorylation and chromatin decondensation in NIH3T3 fibroblasts. Cell Biol Int. 2008; 32(1):107–13. https://doi.org/10.1016/j.cellbi.2007.08.019. PMid:17945518

  • Priante G, Gianesello L, Ceol M, Del Prete D, Anglani F. Cell death in the kidney. Int J Mol Sci. 2019; 20(14):3598. https://doi.org/10.3390/ijms20143598. PMid:31340541. PMCid:PMC6679187

  • Hosten AO. BUN and creatinine. In: Walker HK, Hall WD, Hurst JW, editors. Clinical methods: The history, physical, and laboratory examinations. 3rd ed. Boston: Butterworths; 1990.

  • Chen YC, Yeh JC, Chen HS, Hsu HC. Secondary polycythemia associated with membranous nephropathy. ClinNephrol. 1990; 33(3):148–51.

  • Stark S, Winkelmann B, Kluthe C, Roigas J, Querfeld U, Müller D. Polycythemia and increased erythropoietin in a patient with chronic kidney disease. Nat Rev Nephrol. 2007; 3(4):222–6. https://doi.org/10.1038/ncpneph0437. PMid:17389891

  • Knoblaugh S, True L. Male reproductive system. In: Treuting PM, Dintzis SM, Frevert CW, Liggitt D, Liggitt HD, Montine KS, ed Comparative anatomy and histology: A mouse and human atla. Burlington: Academic Press; 2012. https://doi.org/10.1016/C2009-0-61166-1

  • Yakubu MT. Effect of a 60-day oral gavage of a crude alkaloid extract from Chromolaena odorata leaves on hormonal and spermatogenic indices of male rats. J Androl. 2012; 33(6):1199–207. https://doi.org/10.2164/jandrol.111.016287. PMid:22653963

  • Bruce WR, Heddle JA. The mutagenicity of 61 agents as determined by the micronucleus, Salmonella and sperm abnormality assays. Can J Genet Cytol. 1979; 21(3):319–34. https://doi.org/10.1139/g79-036. PMid:393369

  • Misro MM, Ramya T. Fuel/energy sources of spermatozoa. In: Parekattil S, Agarwal A, editors. Male Infertility. New York: Springer; 2012. https://doi.org/10.1007/978-1-4614-3335-4_21

  • Lázaro DC, López YI, Vázquez AIF, Odio AD, González JE, Sánchez LM, et al. Genotoxic assessment of aqueous extract of Rhizophora mangle L. (mangle rojo) by spermatozoa head assay. Rev Cuba Plantas Med. 2010; 15(1):18–26.

  • Gimmler-Luz MC, Erdtmann B. Effects of a pyrrolizidine alkaloid, integerrimine, on mouse sperm morphology. Rev Int Contam Ambient.1998; 14(2):79–83.

  • Ragasa CY, Espineli DL, Raga DD, Herrera AA, Shen C. Terpenoids from Ardisia squamulosa. Chem Nat Compd. 2013; 49:388–9. https://doi.org/10.1007/s10600-013-0617-x

  • Widyastuti R, Sudiman J, Tyagita T, Syamsunarno MRAA, Sumarsono SH. Oral administration of cogongrass (Imperata cylindrica L) root ethanol-extract causes mouse epididymal sperm abnormality. J Veteriner. 2018; 19(3):351–6.

  • VanHulle K, Lemoine FJ, Narayanan V, Downing B, Hull K, McCullough C, et al. Inverted DNA repeats channel repair of distant double-strand breaks into chromatid fusions and chromosomal rearrangements. Mol Cell Biol. 2007; 27(7):2601–14. https://doi.org/10.1128/MCB.01740-06. PMid:17242181. PMCid:PMC1899885

  • Al-Zubairi AS. Genotoxicity assessment of a natural anti-cancer compound Zerumbone in CHO cell lines. Int J Cancer Res. 2012; 8(4):119–29. https://doi.org/10.3923/ijcr.2012.119.129

  • Abderrahman SM, Soliman S, Mohammad MG. Genotoxic effects of Peganum harmala L. in relation to traditional use. J Pharmacognosy Phytother. 2018; 10(9):167–73.

  • Roy B, Giri BR, Chetia M, Swargiary A. Ultrastructural and biochemical alterations in rats exposed to crude extract of Carex baccans and Potentilla fulgens. Microsc Microanal. 2012; 18(5):1067–76. https://doi.org/10.1017/S1431927612001456. PMid:23067563


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  • Toxicological Assessment of Methanolic Fruit Extract of Zanthoxylum Acanthopodium Dc. In Swiss Albino Mice: Acute and Sub-acute Toxicity Study

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Authors

Armanki Shylla
Department of Zoology, North-Eastern Hill University, Shillong – 793022, Meghalaya,, India
Dondor Pathaw
Department of Zoology, North-Eastern Hill University, Shillong – 793022, Meghalaya,, India
Bishnupada Roy
Department of Zoology, North-Eastern Hill University, Shillong – 793022, Meghalaya,, India

Abstract


Zanthoxylum acanthopodium DC. is widely used in traditional plant-based medical practices in India, with different parts of this plant used to treat a variety of ailments. Though this has been a time-tested practice, the side effects and other implications that the plant may have should not be overlooked. This study evaluated the toxicity of the methanolic fruit extract of Z. acanthopodium in Swiss albino mice by conducting acute and sub-acute toxicity tests using hematological, biochemical, ultrastructural analysis, sperm abnormality, and genotoxicity as parameters. For the acute toxicity test, mice were treated with a single dose of 5000 mg extract/kg bw of mice. While for sub-acute toxicity test, doses of 200, 500, and 1000 mg of the extract/kg bw were administered to the mice. Furthermore, a satellite group of the respective control group and the highest dose group were employed to observe the post-treatment effect that the plant may have. The acute toxicity test resulted in a significant reduction of the mean body weight gain in treated mice, but, no signs of morbidity and mortality were recorded. Sub-acute toxicity test revealed a negative effect of the plant extract on the blood and biochemical parameters. Light and electron microscopic examination of the liver and kidney showed the damaging effects of the extract on the tissues and the cellular structures. In addition, the extract induced sperm abnormalities with a significant reduction of sperm count and sperm viability, and caused an increase in the percentage of abnormally shaped sperms. The extract treatment also resulted in an increased frequency of chromosomal aberrations as well as cell death.

Keywords


Apoptosis, Biochemistry, Chromosomal Aberrations, Hematology, Sperm Abnormality, Ultrastructure, Zanthoxylum acanthopodium.

References





DOI: https://doi.org/10.18311/ti%2F2022%2Fv29i1%2F28051