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Mfoniso Iniobong Udonkang https://orcid.org/0000-0002-5864-1930
Lynette Umasoye Douglas https://orcid.org/0009-0005-1558-1877
Raymond Ekong Eworo https://orcid.org/0000-0003-2139-665X

Abstract

Weeping fig (Ficus benjaminaeaf extract has diverse medicinal properties but little is reported about its hepatotoxicity. This study determined the mean lethal dose (LD50) and investigated the effects of F. benjamina ethanol crude leaf extract on biochemical parameters and liver histology of Sprague Dawley rats. Twenty-nineemale rats weighing 133-204 g were used. The LD50 was determined with nine rats based on Lorke’s method. The experimental groups consisted of twenty rats, divided into four groups of five. Each group received treatment as follows: Control (feed and water only) and low, medium, and high doses (500, 1000, 1500 mg/kg respectively) of the extract orally for 21 days. All animals were weighed and sacrificed using Ketamine intra-peritoneal injection. Blood samples were collected for biochemical parameters of total bilirubin, conjugated bilirubin, aspartate aminotransferase (AST) alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Liver tissues were removed and processed by the formalin-fixed-paraffin wax-embedding method. The tissue blocks were sectioned and subjected to Hematoxylin/Eosin and Masson trichrome staining. The extract’s LD50 was >5000 mg/kg. The rats’ body weights did not change statistically (p=0.985). Total bilirubin (p=0.003), conjugated bilirubin, AST, ALT, and ALP values (p=0.001) increased significantly. The AST high-doseroup had the highest fold increase (4.8). The liver histology showed mild sinusoidal dilation at 500 mg/kg. There was marked hemorrhage and fibrosis at medium and high doses. Although the extract had relatively low acute toxicity, 1000 and 1500 mg/kg doses were associated with mild hepatotoxicity characterized by veno-occlusion disease. The 500 mg/kg dose is safer for medicinal purposes.

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How to Cite
Udonkang, M. I., Douglas, L. U. and Eworo, R. E. (2024) “Ethanol crude leaf extract of weeping fig (Ficus benjamina) causes mild hepatotoxicity in Sprague dawley rats”, Indonesian Journal of Medical Laboratory Science and Technology, 6(2), pp. 85–94. doi: 10.33086/ijmlst.v6i2.5798.
Section
Articles
Bilirubin, Ficus benjamina, Hepatotoxicity, Liver enzymes, Liver histology

References

Wallace AS, Wang D, Shin JI, Selvin E. Screening and diagnosis of prediabetes and diabetes in us children and adolescents. Pediatrics. 2020 Sep; 146(3): e20200265. https://doi.org/10.1542%2Fpeds.2020-0265

Teschke R, Eickhoff A, Schulze J, Danan G. Herb-induced liver injury (HILI) with 12,068 worldwide cases published with causality assessments by Roussel Uclaf Causality Assessment Method (RUCAM): an overview. Transl Gastroenterol Hepatol 2021;6:51. https://doi.org/10.21037/tgh-20-149

Woo SM, Davis WD, Aggarwal S, Clinton JW, Kiparizoska S, Lewis JH. Herbal and dietary supplement induced liver injury: Highlights from the recent literature. World J Hepatol 2021;13(9):1019-1041. https://doi.org/10.4254/wjh.v13.i9.1019

Zheng E, Sandhu N, Navarro V. Drug-induced liver injury secondary to herbal and dietary supplements. Clin Liver Dis. 2020;24:141–155. https://doi.org/doi:10.1016/j.cld.2019.09.009

Ahmad J, Odin JA, Hayashi PH, Fontana RJ, Conjeevaram H, Avula B, Khan IA, Barnhart H, Vuppalanchi R, Navarro VJ; Drug-Induced Liver Injury Network. Liver injury associated with kratom, a popular opioid-like product: Experience from the U.S. drug induced liver injury network and a review of the literature. Drug Alcohol Depend 2021; 218: 108426. https://doi.org/10.1016/j.drugalcdep.2020.108426

Philips, CA, Theruvath, AH. A comprehensive review on the hepatotoxicity of herbs used in the Indian (Ayush) systems of alternative medicine. Medi 2024;103(16):e37903. https://doi.org/10.1097/MD.0000000000037903

Lee BS, Bhatia T, Chaya CT, Wen R, Taira MT, Lim BS. Autoimmune hepatitis associated with turmeric consumption. ACG Case Rep J. 2020; 7:e00320. https://doi.org/10.14309%2Fcrj.0000000000000320

Singh R, Khalid M, Batra N, Biswas P, Singh L, Bhatti R. Exploring the anticonvulsant activity of aqueous extracts of Ficus benjamina L. Figs in experimentally induced convulsions. J Chem. 2023; 1-8. https://doi.org/10.1155/2023/6298366

Okorie N, Obeagu EI, Obinna EK, Agada UN, Obi AI, Uzor S, Ogbonna NI, Uche BM, Ewa IO, Nwovu A. Histopathological evaluation of Ficus capensis aqueous extract on liver, kidney, intestine and its potentials in treatment of anaemia. J Pharma Res Inter. 2021; 33(51A): 271–288. https://doi.org/10.9734/jpri/2021/v33i51A33493

Obafemi FA, Ada AI. A review on Ficus benjamina as a potential viable candidate in the struggle against cancer. J Global Biosc. 2023; 12(3): 9674-9729. https://www.mutagens.co.in/jgb/vol.12/120303.pdf

Kaur P, Sharma R and Agnihotri S: Ficus benjamina: Phytochemical and pharmacognostical perspective. Int J Pharm Sci Res 2023; 14(1): 71-79. http://www.doi.org/10.13040/IJPSR.0975-8232.14(1).71-79

Ogba OM, Udoh DI, Udonkang MI, Eyo A.-AO, Chukwueke SE, Eshemitan Z, Akpan, NG. Antimicrobial effect of Cassia alata leaf extracts on fungal isolates from tinea infections. Trop J Nat Prod Res. 2023; 7(5), 3034–3037. http://www.doi.org/10.26538/tjnpr/v7i5.29

Asuquo GO, Udonkang MI, Oboma YI, Bassey IE, Beshe BS, Okechi OO, Owo DU, Effiong GS. Gongronema latifolium ethanol crude leaf extract ameliorates organ injuries via anti-inflammatory and anti-diabetic mechanisms in streptozotocin-induced diabetic rats. Trop J Nat Prod Res. 2023; 7(8):3823-8. http://www.doi.org/10.26538/tjnpr/v7i8.38

Ofem OE, Udonkang MI, Ogba OM, Bassey IE, Okechi OO. Cyperus esculentus (tiger nut) improves fertility and testicular histology in male sprague dawley rats. Trop J Nat Prod Res. 2023; 7(12):5670-5676. http://www.doi.org/10.26538/tjnpr/v7i12

Carroti S, Morini S, Carpino G, Gaudio E,. Chapter: Liver histology in liver diseases, 2020; SpringerLink, London, p17-28. https://link.springer.com/book/10.1007/978-3-030-24432-3

Shrivastava RK, Kumari P, Jaiswal P, Yadav S, Sharma M. An evaluation of in-vitro & in-vivo hepatoprotective potential of Ficus benjamina Linn. against CCl4 induced toxicity. J New Zealand Herpetol, 2023 12(02),1321-1327. https://biogecko.co.nz/admin/uploads/BioGecko%20_Mukesh%20Sharma.pdf

Pilapil AL, Luscano N, Luciano RM, Lumbres J, Maclan PJ, Managuelod IM, et al. Hepatoprotective effect of crude aqueous leaf extract of fig tree, Ficus benjamina, on ethanol-induced liver damage in mice. Inter J Scientific & Tech Res 2017; 6(06): 118. https://www.ijstr.org/final-print/june2017/Hepatoprotective-Effect-Of-Crude-Aqueous-Leaf-Extract-Of-Fig-Tree-Ficus-Benjamina-On-Ethanol-induced-Liver-Damage-In-Mice.pdf

El Ghouizi A, Ousaaid D, Laaroussi H, et al. Ficus carica (Linn.) leaf and bud extracts and their combination attenuates type-1 diabetes and its complications via the inhibition of oxidative stress. Foods. 2023; 12(4):759. https://doi.org/10.3390/foods12040759

Udonkang MI, Eluwa M, Enun BK, Inyang-Etoh P, Inyang I. Studies on antimalarial activity and liver histopathological changes of Artocarpus altilis on Plasmodium berghi-infected mice. Res J Life Sci Bioinform, Pharma Chem Sci. 2018; 4(3): 106-114. http://www.doi.org/10.26479/2018.0403.09

Jendrassik, L, Grof, P. Colorimetric determination of bilirubin. Biochem Z 1938, 297: 81. https://www.scribd.com/document/485510397/Bili-total-randox

Reitman S, Frankel SA. Colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Ame J Clin Pathol. 1957, 28(1): 56–63. https://doi.org/10.1093/ajcp/28.1.56

Rec GSC. Colorimetric method for serum alkaline phosphatase determination. J Clin Chem Clin Biochem 1972;10: 182-184. https://www.betalab-eg.com/wp-content/uploads/2020/06/AP542.pdf

Bancroft JD, Suvarna SK, Layton C. Bancroft’s theory and practice of histological techniques, 8th ed. London: Elsevier: 2019; 124-172. https://www.sciencedirect.com/book/9780702068874/bancrofts-theory-and-practice-of-histological-techniques

Ladaf SB, Malpani A, Ali N. Diuretic activity and acute oral toxicity study of ethanolic extract of leaves of Ficus benjamina L. in Wistar albino rats. J Pharmacogn Phytochem. 2023; 12(6): 337-344. https://doi.org/10.22271/phyto.2023.v12.i6d.14801

Chike-Ekwughe A, John-Africa LB, Adebayo AH, Ogunlana OO. Evaluation of the toxic effects of ethanolic leaf extract of Tapinanthus cordifolius in mice and rats. Trop J Nat Prod Res. 2023; 7(10):4965-4972. http://www.doi.org/10.26538/tjnpr/v7i10.37

Department Of Environmental Safety, Sustainability & Risk (ESSR). Acute toxin fact sheet, University Of Maryland. 2021: 1-3. https://essr.umd.edu/sites/default/files/2021-10/AcuteToxinsFactSheet.pdf

Kalas MA, Chavez L, Leon M, Taweesedt PT, Surani S. Abnormal liver enzymes: A review for clinicians. World J. Hepatol. 2021; 13(11):1688-1698. http://www.doi.org/10.4254/wjh.v13.i11.1688

Hasti S, Morg E, Utami R, Yulis LU. Sub-chronic toxicity of Ficus benjamina L. leaves ethanol extract on the liver function of white mice. Procedia Chem. 2014; 13, 204-208. https://doi.org/10.1016/j.proche.2014.12.028

Chukwudoruo CS, Osuji-Kalu-Ibe NC, Igwe KO, Iheme CI, Ujowundu FN, Mba AB. Serum total protein concentration and liver enzymes activities in albino rats model administered with ethanolic leaf extract of Ficus capensis. Afri J Biotech. 2021: 20(4): 164-168. https://academicjournals.org/journal/AJB/article-abstract/F29B1F266716

Ma J, Li M, Li N, Chan WY, Lin G. Pyrrolizidine alkaloid-induced hepatotoxicity associated with the formation of reactive metabolite-derived pyrrole–protein adducts. Toxins. 2021; 13(10):723. https://doi.org/10.3390/toxins13100723

Singh B, Sharma RA. Updated review on Indian Ficus species. Arabian J Chem 2023; 16(8):104976. https://doi.org/10.1016/j.arabjc.2023.104976

Lin JK-S, Tujios SR. Hidden dangers: herbal and dietary supplement induced hepatotoxicity. Livers. 2023; 3(4):618-636. https://doi.org/10.3390/livers3040041

Satué K, Miguel-Pastor L, Chicharro D, Gardón JC. Hepatic enzyme profile in horses. Animals. 2022; 12(7):861-865. https://doi.org/10.3390/ani12070861

Udonkang M, Ugbem T, Eze I, Ofem E, Akom A, Johnson S, Onwineng D. Pattern of immunohistochemical expression of inherited breast cancer genes and collagen changes among African women with early breast cancer in Calabar, Nigeria. Global J Pure Appl Sci. 2021; 27(3): 327-34. https://dx.doi.org/10.4314/gjpas.v27i3.8

Wang Z, Jeffrey GP, Huang Y, De Boer B, Garas G, Wallace M, Bertot L, Adams LA. Liver fibrosis quantified by image morphometry predicts clinical outcomes in patients with non-alcoholic fatty liver disease. Hepatol Int. 2023; 17(5): 1162–1169. https://doi.org/10.1007/s12072-023-10564-3

Eworo RE, Ntamu NA, Fabian UA, Thomas CC, Nsonwu MC, Egom OU, Basake RU, Essien AR, Ekam-Ukere IM, Nsonwu-Anyanwu AC. Evaluation of the diagnostic and predictive Performance of non-invasive models for assessing Liver fibrosis in patients with chronic hepatitis B Virus infection. Global J Pure Appl Sci. 2023; 29: 255-265. https://dx.doi.org/10.4314/gjpas.v29i2.15

Adetuyi BO, Adebisi OA, Aletuyi OA, Ogunlana OO. et al. Ficus exasperata attenuates acetaminophen -induced hepatic damage via Nf–αβ signaling mechanism in experimental rat model. Biomed Res. Int. 2022; 6032511. http://www.doi.org/10.1155/2022/6032511

Mfoniso Iniobong Udonkang, University of Calabar

Department of Histopathology and Cytology, Faculty of Medical Laboratory Science, University of Calabar, Calabar, Nigeria

Lynette Umasoye Douglas, University of Calabar

Department of Histopathology and Cytology, Faculty of Medical Laboratory Science, University of Calabar, Calabar, Nigeria

Raymond Ekong Eworo, University of Calabar

Department of Clinical Chemistry and Immunology, Faculty of Medical Laboratory Science, University of Calabar, Calabar, Nigeria