Research Articles

Vol. 2 (2025): Trends in Pharmacy

Prophylactic Effect of Apigenin Against Bisphenol A-Induced Hepatotoxicity

Main Article Content

Mehmet Berköz

Abstract

Background: Bisphenol A (BPA) is the most widely used endocrine disruptor in the world. As the liver is the main organ involved in the detoxification and metabolism of BPA, it is one of the organs most affected by BPA poisoning. No study has investigated the potential effect of apigenin (APG) on BPA-induced hepatotoxicity. This study was conducted to investigate the possible hepatoprotective effects of APG against subacute BPA intoxication in rats.


Methods: Twenty-eight rats were randomly divided into 4 groups: (i) control, (ii) BPA (130 mg/kg), (iii) BPA (130 mg/kg) + APG100 (100 mg/kg), and (iv) BPA (130 mg/kg) + APG200 (200 mg/kg). Both BPA and APG were administered daily by gavage for a total of 28 days. At the end of the experiment, all animals were sacrificed and serum liver function parameters, markers of oxidative stress and inflammation in liver tissue, and histopathological analysis of the liver were assessed.


Results: Bisphenol A pre-treatment impaired liver function tests, induced oxidative stress and inflammatory response, and disrupted liver microarchitecture. Apigenin pre-treatment improved liver function tests, suppressed oxidative stress and inflammation, and, especially high doses, normalized liver microarchitecture.


Conclusion: It is observed that apigenin pre-treatment has a hepatoprotective effect, both biochemical and histological, in eliminating the hepatotoxicity caused by BPA administration.

Cite this article as: Berköz, M. Prophylactic effect of apigenin against bisphenol A-induced hepatotoxicity. Trends in Pharmacy,2025, 2, 0006, doi: 10.5152/TrendsPharm.2025.25003.

Article Details

References

1. Devi T, Saleh NM, Kamarudin NHN, Roslan NJ, Jalil R, Hamid HA. Efficient adsorption of organic pollutants phthalates and bisphenol A (BPA) utilizing magnetite functionalized covalent organic frameworks (MCOFs): a promising future material for industrial applications. Ecotoxicol Environ Saf. 2023;268:115706. [CrossRef]

2. Encarnação T, Pais AA, Campos MG, Burrows HD. Endocrine disrupting chemicals: impact on human health, wildlife and the environment. Sci Prog. 2019;102(1):3-42. [CrossRef]

3. Li X, Ying GG, Su HC, Yang XB, Wang L. Simultaneous determination and assessment of 4-nonylphenol, bisphenol A and triclosan in tap water, bottled water and baby bottles. Environ Int. 2010;36(6):557-562. [CrossRef]

4. Fisher M, Arbuckle TE, MacPherson S, Braun JM, Feeley M, Gaudreau É. Phthalate and BPA exposure in women and newborns through personal care product use and food packaging. Environ Sci Technol. 2019;53(18):10813-10826. [CrossRef]

5. Rubin BS. Bisphenol A: an endocrine disruptor with widespread exposure and multiple effects. J Steroid Biochem Mol Biol. 2011;127(1-2):27-34. [CrossRef]

6. Vom Saal FS, Nagel SC, Coe BL, Angle BM, Taylor JA. The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity. Mol Cell Endocrinol. 2012;354(1-2):74-84. [CrossRef]

7. Shi R, Liu Z, Liu T. The antagonistic effect of bisphenol A and nonylphenol on liver and kidney injury in rats. Immunopharmacol Immunotoxicol. 2021;43(5):527-535. [CrossRef]

8. Abdel-Rahman HG, Abdelrazek HMA, Zeidan DW, Mohamed RM, Abdelazim AM. Lycopene: hepatoprotective and antioxidant effects toward bisphenol A-induced toxicity in Female Wistar Rats. Oxid Med Cell Longev. 2018;2018:5167524. [CrossRef]

9. Uzunhisarcikli M, Aslanturk A. Hepatoprotective effects of curcumin and taurine against bisphenol A-induced liver injury in rats. Environ Sci Pollut Res Int. 2019;26(36):37242-37253. [CrossRef]

10. Wang C, Feng X, Li W, et al. Apigenin as an emerging hepatoprotective agent: current status and future perspectives. Front Pharmacol. 2024;15:1508060. [CrossRef]

11. Alam W, Rocca C, Khan H, et al. Current status and future perspectives on therapeutic potential of apigenin: focus on metabolic-syndrome-dependent organ dysfunction. Antioxidants (Basel). 2021;10(10):1643. [CrossRef]

12. Singh A, Singh J, Parween G, Khator R, Monga V. A comprehensive review of apigenin a dietary flavonoid: biological sources, nutraceutical prospects, chemistry and pharmacological insights and health benefits. Crit Rev Food Sci Nutr. 2024:1-37. [CrossRef]

13. Naponelli V, Rocchetti MT, Mangieri D. Apigenin: molecular mechanisms and therapeutic potential against cancer spreading. Int J Mol Sci. 2024;25(10):5569. [CrossRef]

14. Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharm Res. 2010;27(6):962-978. [CrossRef]

15. Gajender MA, Mazumder A, Sharma A, Azad MAK. A comprehensive review of the pharmacological importance of dietary flavonoids as hepatoprotective agents. Evid Based Complement Alternat Med. 2023;2023:4139117. [CrossRef]

16. Zhou RJ, Ye H, Wang F, Wang JL, Xie ML. Apigenin inhibits d-galactosamine/LPS-induced liver injury through upregulation of hepatic Nrf-2 and PPARγ expressions in mice. Biochem Biophys Res Commun. 2017;493(1):625-630. [CrossRef]

17. Albrahim T, Binobead MA. Moringa oleifera Leaf extract in improving the impact of high dietary intake of monosodium glutamate-induced liver toxicity, oxidative stress, genotoxicity, DNA damage, and PCNA alterations in male ratsRoles of. Oxid Med Cell Longev. 2018;2018:4501097. [CrossRef]

18. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-358. [CrossRef]

19. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497-500. [CrossRef]

20. Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-126. [CrossRef]

21. Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963;61:882-888.

22. Wang X, Ling W, Zhu Y, et al. Spermidine alleviates copper-induced oxidative stress, inflammation and cuproptosis in the liver. FASEB J. 2025;39(6):e70453. [CrossRef]

23. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-275. [CrossRef]

24. Yousefi-Manesh H, Dehpour AR, Ansari-Nasab S, et al. Hepatoprotective effects of standardized extracts from an ancient Italian apple variety (Mela Rosa dei monti sibillini) against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Molecules. 2020;25(8):1816. [CrossRef]

25. Aydın M, Köse E, Taşlıdere Karaca E, Tanbek K, Sandal S. Investigation of the protective effect of Lavandula stoechas against the damage caused by bisphenol A in the liver tissue of rats. Heliyon. 2024;10(20):e39386. [CrossRef]

26. Kobayashi A, Suzuki Y, Sugai S. Specificity of transaminase activities in the prediction of drug-induced hepatotoxicity. J Toxicol Sci. 2020;45(9):515-537. [CrossRef]

27. Islam MT, Quispe C, Islam MA, et al. Effects of nerol on paracetamol-induced liver damage in Wistar albino rats. Biomed Pharmacother. 2021;140:111732. [CrossRef]

28. Scheig R. Evaluation of tests used to screen patients with liver disorders. Prim Care. 1996;23(3):551-560. [CrossRef]

29. 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;394(3):523-531. [CrossRef]

30. Al-Amarat W, Abukhalil MH, Alruhaimi RS, et al. Upregulation of Nrf2/HO-1 signaling and attenuation of oxidative stress, inflammation, and cell death mediate the protective effect of apigenin against cyclophosphamide hepatotoxicity. Metabolites. 2022;12(7):648. [CrossRef]

31. Ali F, Rahul NF, Naz F, Jyoti S, Siddique YH. Protective effect of apigenin against N-nitrosodiethylamine (NDEA)-induced hepatotoxicity in albino rats. Mutat Res Genet Toxicol Environ Mutagen. 2014;767:13-20. [CrossRef]

32. Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem. 2015;97:55-74. [CrossRef]

33. Babu S, Uppu S, Claville MO, Uppu RM. Prooxidant actions of bisphenol A (BPA) phenoxyl radicals: implications to BPA-related oxidative stress and toxicity. Toxicol Mech Methods. 2013;23(4):273-280. [CrossRef]

34. Yue S, Xue N, Li H, Huang B, Chen Z, Wang X. Hepatoprotective effect of apigenin against liver injury via the non-canonical NF-κB pathway in vivo and in vitro. Inflammation. 2020;43(5):1634-1648. [CrossRef]

35. Wang E, Chen F, Hu X, Yuan Y. Protective effects of apigenin against furan-induced toxicity in mice. Food Funct. 2014;5(8):1804-1812. [CrossRef]

36. Arita Y, Park HJ, Cantillon A, Getahun D, Menon R, Peltier MR. Effect of bisphenol-A (BPA) on placental biomarkers for inflammation, neurodevelopment and oxidative stress. J Perinat Med. 2019;47(7):741-749. [CrossRef]

37. Abdulhameed AAR, Lim V, Bahari H, et al. Adverse effects of bisphenol A on the liver and its underlying mechanisms: evidence from in vivo and in vitro studies. BioMed Res Int. 2022;2022:8227314. [CrossRef]

38. Sahindokuyucu-Kocasari F, Akyol Y, Ozmen O, Erdemli-Kose SB, Garli S. Apigenin alleviates methotrexate-induced liver and kidney injury in mice. Hum Exp Toxicol. 2021;40(10):1721-1731. [CrossRef]