JOURNAL OF ANIMAL SCIENCE AND VETERINARY MEDICINE
Integrity Research Journals
ISSN: 2536-7099
Model: Open Access/Peer Reviewed
DOI: 10.31248/JASVM
Start Year: 2016
Email: jasvm@integrityresjournals.org
Ethanol extract of Ficus exasperata leaf and gallic acid ameliorate cisplatin-induced toxicity in Wistar rats
https://doi.org/10.31248/JASVM2025.588 | Article Number: 03B048FB10 | Vol.10 (3) - June 2025
Received Date: 24 May 2025 | Accepted Date: 27 June 2025 | Published Date: 30 June 2025
Authors: Olumuyiwa Abiola Adejumobi* , Mayowa David Oloko , Oladipo O. Omotosho , John O. Abiola , Olamilekan Gabriel Banwo , Olumide Odunayo Akinniyi , Tola Felicia Ajani , Ademola A. Oyagbemi , Adeolu Alex Adedapo , Momoh A. Yakubu and Temidayo O. Omóbòwálé
Keywords: Wistar Rats., oxidative stress, antioxidant, cardio-renal toxicity, cisplatin, Ficus exasperata, gallic acid
Cisplatin (CP), a widely used platinum-based chemotherapeutic, is effective in cancer treatment but it is associated with significant multiple organ toxicity, particularly the liver, kidneys, gastrointestinal tract, and cardiovascular system. Oxidative stress is a major contributor to this toxicity. This study aimed to investigate the protective effects of Ficus exasperata (FE) extract and gallic acid (GA), both known for their antioxidant properties, against cisplatin-induced toxicity, oxidative stress, and organ damage in Wistar rats. Fifty male Wistar rats (162–266 g) were randomly assigned to five groups (A–E; n=10). Group A received distilled water only (control). Group B was administered cisplatin (10 mg/kg, intraperitoneally) on day 8. Groups C and D received 100 mg/kg and 200 mg/kg of Ficus exasperata extract orally for 8 days, respectively, followed by cisplatin administration on day 8. Group E received gallic acid (100 mg/kg orally) for 8 days and cisplatin on day 8. Blood pressure and ECG measurements were taken before sacrifice. Blood, liver, kidney, and heart samples were analyzed for oxidative stress markers, antioxidant enzyme activities, hematological, liver, and renal function indices. Cisplatin administration significantly elevated systolic blood pressure and markers of oxidative stress, while reducing antioxidant enzyme levels in cardiac and renal tissues. Treatment with FE and GA significantly reduced oxidative stress and restored antioxidant enzyme levels. The 200 mg/kg dose of Ficus exasperata showed the most pronounced protective effect. FE and GA exert protective effects against cisplatin-induced cardio-renal toxicity in rats, likely through antioxidant activity. The protective effect of Ficus exasperata appears dose-dependent.
| Abdel-Gayoum, A. A., & Ahmida, M. H. S. (2017). Changes in the serum, liver, and renal cortical lipids and electrolytesin rabbits with cisplatin-induced nephrotoxicity. Turkish Journal of Medical Sciences, 47(3), 1019-1027. https://doi.org/10.3906/sag-1602-136 |
||||
| Adekeye, O. A., Adetunji, C. O., Adetunji, J. B., & Okunlola, O. A. (2020). Ethnobotanical survey of medicinal plants used in the treatment of reproductive health disorders among the Yoruba people of Nigeria. Journal of Medicinal Plants Research, 14(5), 149-160. | ||||
| Adetuyi, B. O., Adebisi, O. A., Adetuyi, O. A., Ogunlana, O. O., Toloyai, P. E., Egbuna, C., ... & Patrick-Iwuanyanwu, K. C. (2022). Ficus exasperata attenuates acetaminophen-induced hepatic damage via NF-κB signaling mechanism in experimental rat model. BioMed Research International, Volume 2022, Article ID 6032511, 10 pages. https://doi.org/10.1155/2022/6032511 |
||||
| Afsar, B., Bakan, E., & Covic, A. (2015). The relationship between serum uric acid level and chronic kidney disease. International Urology and Nephrology, 47(4), 547-555. | ||||
| Ajeigbe, O. F., Oboh, G., Ademosun, A. O., & Oyagbemi, A. A. (2021). Fig leaves varieties reduce blood pressure in hypertensive rats through modulation of antioxidant status and activities of arginase and angiotensin-1 converting enzyme. Comparative Clinical Pathology, 30, 503-513. https://doi.org/10.1007/s00580-021-03244-x |
||||
| Akanni, E. O., Olopade, J. O., & Omisore, N. O. (2014). Antiproliferative and antioxidant activities of Ficus exasperata on human ovarian cancer cells in vitro. Journal of Intercultural Ethnopharmacology, 3(2), 59-64. | ||||
| Akhtar, M. S., & Swamy, M. K. (2018). Anticancer and anti-inflammatory activities of some dietary cucurbits. International Journal of Molecular Sciences, 19(4), 974. | ||||
| Alkreathy, H. M., Khan, L. M., & Al-Essa, M. S. (2014). In vitro and in vivo anti-tumor effects of some Saudi Arabian plants. Saudi Journal of Biological Sciences, 21(2), 147-153. | ||||
| Babbar, P., Lokanatha, D., Jacob, L. A., Babu, M. S., Lokesh, K. N., Rudresha, A. H., ... & Kakkar, V. (2020). Cardiotoxic effect of chemotherapeutic agents. European Journal of Molecular & Clinical Medicine, 7(10), 2020. | ||||
| Bagavan, A., Rahuman, A. A., Kaushik, N. K., & Sahal, D. (2011). In vitro antimalarial activity of medicinal plant extracts against Plasmodium falciparum. Parasitology Research, 108(1), 15-22. https://doi.org/10.1007/s00436-010-2034-4 |
||||
| Bakr, A. H., Moustafa, A. M., Hafez, H. F., Attia, A. S., & El-Abhar, H. S. (2019). The potential protective effect of thymoquinone against renal injury secondary to ischemia/reperfusion in rats. Biomedicine & Pharmacotherapy, 109, 2479-2486. | ||||
| Bari, M. W., Islam, M. M., Khatun, M., Sultana, M. J., Ahmed, R., Islam, A., ... & Islam, M. A. (2020). Antidiabetic effect of Wedelia chinensis leaf extract in alloxan induced Swiss albino diabetic mice. Clinical Phytoscience, 6, 49. https://doi.org/10.1186/s40816-020-00197-6 |
||||
| Bator, E. E., Adeleke, O. O., Adegbola, P. I., Ogundajo, A. L., Oluwalana, S. A., & Oladunmoye, M. K. (2017). Ficus exasperata leaf extract ameliorates renal oxidative stress in STZ-induced diabetic rats. Pathophysiology, 24(1), 59-68. | ||||
| Bukhari, I. A., Mohamed, O. Y., Alhowikan, A. M., Lateef, R., Hagar, H., Assiri, R. A., ... & Alqahtani, W. A. M. (2022). Protective effect of rutin trihydrate against dose-dependent, cisplatin-induced cardiac toxicity in isolated perfused rat's heart. Cureus, 14(1), e21572 https://doi.org/10.7759/cureus.21572 |
||||
| Dasari, S., Njiki, S., Mbemi, A., Yedjou, C. G., & Tchounwou, P. B. (2022). Pharmacological effects of cisplatin combination with natural products in cancer chemotherapy. International journal of molecular sciences, 23(3), 1532. https://doi.org/10.3390/ijms23031532 |
||||
| Dugbartey, G. J., Bouma, H. R., Lobb, I., & Sener, A. (2016). Hydrogen sulfide: a novel nephroprotectant against cisplatin-induced renal toxicity. Nitric Oxide, 57, 15-20. https://doi.org/10.1016/j.niox.2016.04.005 |
||||
| Eslamifar, Z., Moridnia, A., Sabbagh, S., Ghaffaripour, R., Jafaripour, L., & Behzadifard, M. (2021). Ameliorative effects of Gallic acid on cisplatin‐induced nephrotoxicity in rat variations of biochemistry, histopathology, and gene expression. BioMed Research International, 2021(1), 2195238. https://doi.org/10.1155/2021/2195238 |
||||
| Faiyaz, S., Alam, Q., Ahmad, S., & Ismail, S. (2012). A review on phytochemical and pharmacological investigations of miswak (Salvadora persica Linn). Journal of Pharmacy & Bioallied Sciences, 4(Suppl 2), S280-S282. | ||||
| Florea, A. M., & Büsselberg, D. (2011). Cisplatin as an anti-tumor drug: Cellular mechanisms of activity, drug resistance and induced side effects. Cancers, 3(1), 1351-1371. https://doi.org/10.3390/cancers3011351 |
||||
| Gao, Y., Wang, J., Zhou, Y., Sheng, S., Qian, S. Y., & Huo, T. (2019). Gallic acid ameliorates non-alcoholic fatty liver disease (NAFLD) and insulin resistance: A randomized, placebo-controlled and double-blinded clinical trial. Journal of Functional Foods, 52, 450-458. | ||||
| Herradón, E., González, C., Uranga, J. A., Abalo, R., Martín, M. I., & López-Miranda, V. (2017). Characterization of cardiovascular alterations induced by different chronic cisplatin treatments. Frontiers in Pharmacology, 8, 196. https://doi.org/10.3389/fphar.2017.00196 |
||||
| Karale, S., & Kamath, J. V. (2017). Effect of daidzein on cisplatin-induced hematotoxicity and hepatotoxicity in experimental rats. Indian Journal of Pharmacology, 49(1), 49-54. https://doi.org/10.4103/0253-7613.201022 |
||||
| Katanić Stanković, J. S., Selaković, D., & Rosić, G. (2023). Oxidative damage as a fundament of systemic toxicities induced by cisplatin-the crucial limitation or potential therapeutic target? International Journal of Molecular Sciences, 24(19), 14574. https://doi.org/10.3390/ijms241914574 |
||||
| Kumar, P., Barua, C. C., Sulakhiya, K., & Sharma, R. K. (2017). Curcumin ameliorates cisplatin-induced nephrotoxicity and potentiates its anticancer activity in SD rats: Potential role of curcumin in breast cancer chemotherapy. Frontiers in Pharmacology, 8, 132. https://doi.org/10.3389/fphar.2017.00132 |
||||
| Li, F., Yao, Y., Huang, H., Hao, H., & Ying, M. (2018). Xanthohumol attenuates cisplatin-induced nephrotoxicity through inhibiting NF-κB and activating Nrf2 signaling pathways. International Immunopharmacology, 61, 277-282. https://doi.org/10.1016/j.intimp.2018.05.017 |
||||
| Lin, X., Okuda, T., Holzer, A., & Howell, S. B. (2022). The copper transporter CTR1 regulates cisplatin uptake in Saccharomyces cerevisiae. Molecular Pharmacology, 62(5), 1154-1159. https://doi.org/10.1124/mol.62.5.1154 |
||||
| Liu, C., Liang, J., Zhou, X., Xie, L., Li, W., Liu, S., & Li, X. (2014). Gallic acid attenuates lipopolysaccharide-induced acute lung injury in mice. Inflammation, 37(1), 1-9. | ||||
| Maheshwari, R. A., Sailor, G. U., Sen, A. K., & Balaraman, R. (2015). Amelioration of cisplatin-induced hepatotoxicity by statins in rats. Journal of Integrated Health Sciences, 3(1), 21-27. https://doi.org/10.4103/2347-6486.238515 |
||||
| Makovec, T. (2019). Cisplatin and beyond: Molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiology and Oncology, 53(2), 148-158. https://doi.org/10.2478/raon-2019-0018 |
||||
| Martins, N. M., Santos, N. A. G. D., Curti, C., Bianchi, M. D. L. P., & Santos, A. C. D. (2008). Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver. Journal of Applied Toxicology: An International Journal, 28(3), 337-344. https://doi.org/10.1002/jat.1284 |
||||
| McSweeney, K. R., Gadanec, L. K., Qaradakhi, T., Ali, B. A., Zulli, A., & Apostolopoulos, V. (2021). Mechanisms of cisplatin-induced acute kidney injury: Pathological mechanisms, pharmacological interventions, and genetic mitigations. Cancers, 13(7), 157. https://doi.org/10.3390/cancers13071572 |
||||
| Mikail, H. G., Ahmadu, A. A., Umar, I. A., & Yaro, A. H. (2019). Phytochemical analysis and evaluation of the anti-inflammatory and antioxidant properties of Ficus exasperata Vahl. (Moraceae) root bark extract. Journal of Complementary and Integrative Medicine, 16(4), 1-8. | ||||
| Mouho, H. M., Tchimene, M. K., Hilaire, M. F. M., Yolande, S. N., Felicite, M. A. N., & Pierre, M. J. (2018). Phytochemical analysis of the bark extract of Ficus exasperata Vahl (Moraceae) from Cameroon. Asian Journal of Plant Science and Research, 8(3), 9-16. | ||||
| Oladele, J., Oyewole, O., Bello, O., & Oladele, O. (2017). Assessment of protective potentials of Ficus exasperata leaf on arsenate-mediated dyslipidemia and oxidative damage in rat's brain. Journal of Basic and Applied Research in Biomedicine, 3(3), 89-94. | ||||
| Omobowale, T. O., Oyagbemi, A. A., Ajufo, U. E., Adejumobi, O. A., Ola-Davies, O. E., Adedapo, A. A., & Yakubu, M. A. (2018). Ameliorative effect of gallic acid in doxorubicin-induced hepatotoxicity in Wistar rats through antioxidant defense system. Journal of Dietary Supplements, 15(2), 183-196. https://doi.org/10.1080/19390211.2017.1335822 |
||||
| Oyagbemi, A. A., Omobowale, T. O., Asenuga, E. R., Akinleye, A. S., Ogunsanwo, R. O., & Saba, A. B. (2016). Cyclophosphamide-induced hepatotoxicity in Wistar rats: The modulatory role of gallic acid as a hepatoprotective and chemopreventive phytochemical. International Journal of Preventive Medicine, 7, 51. https://doi.org/10.4103/2008-7802.177898 |
||||
| Papavramidou, N., Papavramidis, T., & Demetriou, T. (2010). Ancient Greek and Greco-Roman methods in modern surgical treatment of cancer. Annals of Surgical Oncology, 17, 665-667. https://doi.org/10.1245/s10434-009-0886-6 |
||||
| Prasaja, Y., Sutandyo, N., & Andrajati, R. (2015). Incidence of cisplatin-induced nephrotoxicity and associated factors among cancer patients in Indonesia. Asian Pacific Journal of Cancer Prevention, 16(3), 1117-1122. https://doi.org/10.7314/APJCP.2015.16.3.1117 |
||||
| Ratliff, B. B., Abdulmahdi, W., Pawar, R., & Wolin, M. S. (2016). Oxidant mechanisms in renal injury and disease. Antioxidants & Redox Signaling, 25(3), 119-146. https://doi.org/10.1089/ars.2016.6665 |
||||
| Ray, P. D., Huang, B. W., & Tsuji, Y. (2012). Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cellular Signalling, 24(5), 981-990. https://doi.org/10.1016/j.cellsig.2012.01.008 |
||||
| Regginato, F. H., Mioskowski, E., de Oliveira, A. L., & da Silva, J. J. (2021). Plants as a source of potential therapeutic compounds for COVID-19. Phytochemistry Reviews, 20(5), 1265-1281. | ||||
| Sahreen, S., Khan, M. R., & Khan, R. A. (2017). Evaluation of antioxidant profile of various solvent extracts of Carissa opaca leaves: an edible plant. Chemistry Central Journal, 11(1), 83. https://doi.org/10.1186/s13065-017-0300-6 |
||||
| Wang, R., Li, Y. B., Li, Y. H., Xu, Y., Wu, H. L., Li, X. J., & Sun, C. H. (2019). Pterostilbene attenuates inflammation in rat heart subjected to ischemia-reperfusion: Role of TLR4/NF-κB signaling pathway. International Immunopharmacology, 75, 105730. | ||||
| Wheate, N. J., Walker, S., Craig, G. E., & Oun, R. (2010). The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton Transactions, 39(35), 8113-8127. https://doi.org/10.1039/c0dt00292e |
||||
| Zhao, Y., Asimi, S., Wu, K., Zheng, J., Li, D., Sun, Q., & Chen, Y. (2020). Tea and its components: Update on health-promoting properties. Critical Reviews in Food Science and Nutrition, 60(18), 2939-2953. | ||||
Copyright © 2025 Integrity Research Journals. All rights reserved.