Alleviating Effects of Honey in Albino Wistar Rats with Hematological and Hepatic Variations Provoked by Methotrexate
DOI:
https://doi.org/10.36283/ziun-pjmd14-2/038Keywords:
Methotrexate, Hepatotoxicity, Honey, Morphometry, Liver EnzymesAbstract
Background: Methotrexate is a chemotherapeutic drug with toxic consequences to the liver. Honey has been documented to have healing properties. This study aimed to explore the alleviating effects of Honey in rats with Hematological and Hepatic variations provoked by Methotrexate.
Methods: This experimental research was conducted at Baqai Medical University for one year. 45 male albino Wistar rats were randomly divided into three groups. Control Group A with no intervention, treatment Group B with a single dose of Methotrexate of 20 mg/kg intraperitoneally and protected Group C with 10g/kg honey by gastric gavage for 7 days and 20 mg/kg of Methotrexate on the 4th day. At the end of the experiment, blood and liver samples were collected for liver enzymes and microscopic investigation. SPSS v25.0 was used for statistical analysis, with values as Mean ± SD, ANOVA for group comparisons, post hoc Tukey's test, and p<0.05 considered significant at a 95% confidence interval.
Results: The ultimate body weight of Group B was reduced (162±2.58); whereas the relative and absolute weight of the liver increased (9.54±1.42) and (5.89±0.91) respectively. The levels of ALT (51.27±15.35), AST (103.41±2.68), ALP (353.64±2.54) and albumin (4.19±5.36) in the serum notably increased, while Group C showed significant improvement. Sections from Group A’s liver appeared to have normal parenchyma whereas it was altered in Group B, however Group C showed improvement. The hepatocyte counts per reticule decreased (7.18±1.36) significantly in Group B, while hepatocyte diameter increased (17.6±1.51) and nuclear diameter decreased (5.29±1.41). In contrast, all measurements showed improvement in Group C.
Conclusion: This study indicated that Honey was able to alleviate Methotrexate induced hematological and hepatotoxic alterations.
References
Ezhilarasan D. Hepatotoxic potentials of methotrexate: Understanding the possible toxicological molecular mechanisms. Toxicol. 2021 Jun;458:152840. doi:10.1016/j.tox.2021.152840
Hasan Khudhair D, Al-Gareeb AI, Al-Kuraishy HM, El-Kadem AH, Elekhnawy E, Negm WA, Saber S, Cavalu S, Tirla A, Alotaibi SS, Batiha GE. Combination of vitamin C and curcumin safeguards against methotrexate-induced acute liver injury in mice by synergistic antioxidant effects. Front Med. 2022 Apr;9:866343. doi:10.3389/fmed.2022.866343
Goudarzi M, Kalantar M, Sadeghi E, Karamallah MH, Kalantar H. Protective effects of apigenin on altered lipid peroxidation, inflammation, and antioxidant factors in methotrexate-induced hepatotoxicity. Naunyn Schmiedebergs Arch Pharmacol. 2021 Mar;394:523-531. doi:10.1007/s00210-020-01991-2
Ezhilarasan DJT. Hepatotoxic potentials of methotrexate: Understanding the possible toxicological molecular mechanisms. Toxicol. 2021 Jun;458:152840. doi:10.1016/j.tox.2021.152840
Orhan H, Karakuş F, Ergüç A. Mitochondrial biotransformation of drugs and other xenobiotics. Curr Drug Metab. 2021 Jul;22(8):657-669. doi:10.2174/1389200222666210628125020
Rai M, Paudel N, Sakhrie M, Gemmati D, Khan IA, Tisato V, Kanase A, Schulz A, Singh AV. Perspective on quantitative structure–toxicity relationship (QSTR) models to predict hepatic biotransformation of xenobiotics. Livers. 2023 Aug;3(3):448-462. doi:10.3390/livers3030032
Zhou Y, Wang J, Zhang D, Liu J, Wu Q, Chen J, Tan P, Xing B, Han Y, Zhang P, Xiao X. Mechanism of drug-induced liver injury and hepatoprotective effects of natural drugs. Chin Med. 2021 Dec;16(1):135. doi:10.1186/s13020-021-00543-x
Silva B, Biluca FC, Gonzaga LV, Fett R, Dalmarco EM, Caon T, Costa AC. In vitro anti-inflammatory properties of honey flavonoids: A review. Food Res Int. 2021 Mar;141:110086. doi:10.1016/j.foodres.2020.110086
Anastasiou IA, Eleftheriadou I, Tentolouris A, Samakidou G, Papanas N, Tentolouris N. Therapeutic properties of honey for the management of wounds; is there a role in the armamentarium of diabetic foot ulcer treatment? Results from in vitro and in vivo studies. Int J Low Extrem Wounds. 2021 Dec;20(4):291-299. doi:10.1177/15347346211026819
Afrin S, Haneefa SM, Fernandez-Cabezudo MJ, Giampieri F, Al-Ramadi BK, Battino M. Therapeutic and preventive properties of honey and its bioactive compounds in cancer: An evidence-based review. Nutr Res Rev. 2020 Jun;33(1):50-76. doi:10.1017/S0954422419000192
Akinpelu AT, Akinloye OM, Olubanjo FO, Busuyi KD, Fatoki JO, Stephen OA, Adewale OO. Ameliorative and Synergetic Effects of Co-Administration of Honey and Vernonia amygdalina (Bitter leaf) Extract on Lead-Induced Wistar Rats. Trop J Nat Prod Res. 2024 Jun;8(6). doi:10.26538/tjnpr/v8i6.14
Omar S. The Activity of Some Herbs with or Without Honey in Protecting the Liver against Carbon Tetrachloride Hepatotoxicity in Female Albino Rats. Medicine. 2022 Sep;8(42):173-200. doi:10.21608/jedu.2022.108442.1534
Ghoneum M, El-Gerbed MS. Human placental extract ameliorates methotrexate-induced hepatotoxicity in rats via regulating antioxidative and anti-inflammatory responses. Cancer Chemother Pharmacol. 2021 Dec;88:961-971. doi:10.1007/s00280-021-04349-4
Hamed KM, Dighriri IM, Baomar AF, Alharthy BT, Alenazi FE, Alali GH, Alenazy RH, Alhumaidi NT, Alhulayfi DH, Alotaibi YB, Alhumaidan SS. Overview of methotrexate toxicity: A comprehensive literature review. Cureus. 2022 Sep;14(9). doi: 10.7759/cureus.29518
El-Sheikh AA, Morsy MA, Abdalla AM, Hamouda AH, Alhaider IA. Mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats. Mediat Inflamm. 2015 May;2015(1):859383. doi:10.1155/2015/859383
Ilamkar S, Rathod P, Ingole R, Hajare S, Khodke M. Ameliorative effect of hydro-ethanolic extract of Tinospora cordifolia against methotrexate induced toxicity in mice. J Entom Zool Studies. 2020 Jan;8:505-510. https://www.entomoljournal.com/archives/2020/vol8issue1/PartI/7-4-317-206.pdf
Hassanein EH, Mohamed WR, Khalaf MM, Shalkami AG, Sayed AM, Hemeida RA. Diallyl disulfide ameliorates methotrexate‐induced nephropathy in rats: Molecular studies and network pharmacology analysis. J Food Biochem. 2021 Jun;45(6):e13765. doi:10.1111/jfbc.13765
Abdul-Hamid M, Abdel-Reheim ES, Hegazy W, Allam A, Othman SI, Alwaele MA, Abdel-Kawi SH. Effect of gervital in attenuating hepatotoxicity caused by methotrexate or azathioprine in adult albino rats. Environ Sci Pollut Res Int. 2022 Feb;29(31):46788-46801. doi:10.1007/s11356-022-18903
Di Martino V, Verhoeven DW, Verhoeven F, Aubin F, Avouac J, Vuitton L, Lioté F, Thévenot T, Wendling D. Busting the myth of methotrexate chronic hepatotoxicity. Nat Rev Rheumatol. 2023 Feb;19(2):96-110. doi:10.1038/s41584-022-00883-4
Hoque MR, Razzaque MA, Zawad AN, Rahman SW. Status of Renal and Liver Function in Rheumatoid Arthritis (RA) Patients of Chattogram, Bangladesh Treated with Methotrexate (MTX). J Biosci Med. 2023 Aug;11(9):114-126. doi:10.4236/jbm.2023.119010.
Omidipour R, Zarei L, Boroujeni MB, Rajabzadeh A. Protective effect of thyme honey against valproic acid hepatotoxicity in Wistar rats. BioMed Res Int. 2021 Feb;2021(1):8839898. doi:10.1155/2021/8839898
Solomon DH, Glynn RJ, Karlson EW, Lu F, Corrigan C, Colls J, et al. Adverse effects of low-dose methotrexate: a randomized trial. Ann Intern Med. 2020 Mar;172(6):369-380. doi.org/10.7326/M19-3369
Dogra A, Gupta D, Bag S, Ahmed I, Bhatt S, Nehra E, Dhiman S, Kumar A, Singh G, Abdullah ST, Sangwan PL. Glabridin ameliorates methotrexate-induced liver injury via attenuation of oxidative stress, inflammation, and apoptosis. Life Sci. 2021 Aug;278:119583. doi:10.1016/j.lfs.2021.119583
Tufan E, Sivas GG, Gürel-Gökmen B, Yılmaz-Karaoğlu S, Dursun E, Çalışkan-Ak E, Muhan A, Özbeyli D, Şener G, Tunali-Akbay T. Whey protein concentrate ameliorates the methotrexate-induced liver and kidney damage. Br J Nutr. 2023 Nov;130(10):1704-1711. doi:10.1016/j.lfs.2021.119583
Laaroussi H, Bakour M, Ousaaid D, Ferreira-Santos P, Genisheva Z, El Ghouizi A, Aboulghazi A, Teixeira JA, Lyoussi B. Protective Effect of Honey and Propolis against Gentamicin‐Induced Oxidative Stress and Hepatorenal Damages. Oxidative Med Cell Longev. 2021 Sep;2021(1):9719906. doi:10.1155/2021/9719906
El Kutry MS. Potential protection effect of using honey, ginger, and turmeric as a natural treatment against chemotherapy of intestinal toxicity. J Biol Active Prod Nature. 2020 Mar;10(2):86-99. doi:10.1080/22311866.2020.1745686
Sidabutar DFM, Budijitno S, Prasetyo A . The effectiveness of multiflora honey to prevent hepatotoxicity in invasive ductal breast cancer patients with FAC chemotherapy. Bali Med J. 2021 Dec;10(3):982-987. 7. doi:10.15562/bmj.v10i3.2660

Downloads
Published
Issue
Section
License
Copyright (c) 2025 Pakistan Journal of Medicine and Dentistry

This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an open-access article distributed under the terms of the CreativeCommons Attribution License (CC BY) 4.0 https://creativecommons.org/licenses/by/4.0/