Skip to main navigation menu Skip to main content Skip to site footer
Plant Science Today (PST)

Research Articles

Early Access

Ameliorative effects of eugenol and naringenin on perfluorooctanoic acid-induced hepatotoxicity in Sprague-Dawley rats

DOI
https://doi.org/10.14719/pst.9874
Submitted
6 June 2025
Published
30-03-2026

Abstract

Perfluorooctanoic acid (PFOA), an environmental pollutant with wide industrial usage, is known to induce hepatotoxicity through oxidative stress, inflammation and lipid dysregulation. This study evaluated the hepatoprotective effects of eugenol and naringenin against PFOA–induced liver damage in Sprague-Dawley rats. Hepatotoxicity was induced via the oral administration of PFOA (40 mg/kg) for 21 days. Simultaneously, the rats were treated with eugenol (5 and 10 mg/kg) and naringenin (10 and 50 mg/kg). Serum biochemical parameters like alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol and triglycerides, liver thiobarbituric acid reactive substances (TBARS) levels and histopathological changes were assessed. In silico molecular docking was performed to explore the interactions of the test compounds with adiponectin. PFOA significantly elevated serum transaminases, lipid parameters and hepatic TBARS levels and induced histological changes such as steatosis, necrosis and inflammation. Treatment with eugenol and naringenin significantly (P < 0.05) mitigated these alterations, particularly at higher doses. Molecular docking revealed favourable binding affinities of both compounds with adiponectin, suggesting a mechanistic role in their hepatoprotective effects. Eugenol and naringenin exerted protective effects against PFOA-induced hepatotoxicity through antioxidant, anti–inflammatory and lipid–modulating actions, possibly via adiponectin signalling pathways. These findings highlight their therapeutic potential in managing environmentally induced liver damage.

References

  1. 1. Choi J, Kim JY, Lee HJ. Human evidence of perfluorooctanoic acid exposure on hepatic disease: a systematic review and meta–analysis. Int J Environ Res Public Health. 2022;19(18):11318. https://doi.org/10.3390/ijerph191811318
  2. 2. Ji M, Deng Z, Rong X, Li R, You Z, Guo X, et al. Naringenin prevents oxidative stress and inflammation in LPS–induced liver injury through the regulation of lncRNA–mRNA in male mice. Molecules. 2023;28(1):198. https://doi.org/10.3390/molecules28010198
  3. 3. Damasceno ROS, Pinheiro JLS, Rodrigues LHM, Gomes RC, Duarte ABS, Emídio JJ, et al. Anti–inflammatory and antioxidant activities of eugenol: an update. Pharmaceuticals. 2024;17(11):1505. https://doi.org/10.3390/ph17111505
  4. 4. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes and the metabolic syndrome. J Clin Invest. 2006;116(7):1784–92. https://doi.org/10.1172/JCI29126
  5. 5. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, et al. Adiponectin stimulates glucose utilisation and fatty–acid oxidation by activating AMP–activated protein kinase. Nat Med. 2002;8(11):1288–95. https://doi.org/10.1038/nm788
  6. 6. Dzierlenga AL, Robinson VG, Waidyanatha S, DeVito MJ, Eifrid MA, Gibbs ST, et al. Toxicokinetics of perfluorohexanoic acid, perfluorooctanoic acid and perfluorodecanoic acid in male and female Hsd: Sprague Dawley rats following intravenous or gavage administration. Xenobiotica. 2019;50(6):722–32. https://doi.org/10.1080/00498254.2019.1683776
  7. 7. Sahu N, Mishra G, Chandra HK, Nirala SK. Naringenin mitigates antituberculosis drugs induced hepatic and renal injury in rats. J Tradit Complement Med. 2020;10(1):26–35. https://doi.org/10.1016/j.jtcme.2019.01.001
  8. 8. Binu P, Priya N, Abhilash S, Vineetha RC, Nair H. Protective effects of eugenol against hepatotoxicity induced by arsenic trioxide: an antileukemic drug. Iran J Med Sci. 2018;43(3):305–12.
  9. 9. Harb AA, Bustanji YK, Almasri IM, Abdalla SS. Eugenol reduces LDL cholesterol and hepatic steatosis in hypercholesterolemic rats by modulating TRPV1 receptor. Sci Rep. 2019;9:14003. https://doi.org/10.1038/s41598-019-50352-4
  10. 10. Pari L, Gnanasoundari M. Influence of naringenin on oxytetracycline mediated oxidative damage in rat liver. Basic Clin Pharmacol Toxicol. 2006;98(5):456–61. https://doi.org/10.1111/j.1742–7843.2006.pto_351.x
  11. 11. De Leon JAD, Borges CR. Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay. J Vis Exp. 2020;(159):e61122.
  12. 12. Suvarna KS, Layton C, Bancroft JD. Bancroft's theory and practice of histological techniques. 8th ed. Amsterdam: Elsevier Health Sciences; 2018. p. 84–95.
  13. 13. Sivapria AS, Kariyil BJ, Menon P. In silico screening of phytoconstituents of Cissus quadrangularis and Chromolaena odorata against proteins of antimicrobial resistance and wound healing. Plant Sci Today. 27;11(1):531–43.
  14. 14. Kudo N, Kawashima Y. Toxicity and toxicokinetics of perfluorooctanoic acid in humans and animals. J Toxicol Sci. 2003;28(2):49–57. https://doi.org/10.2131/jts.28.49
  15. 15. Das KP, Wood CR, Lin MT, Starkov AA, Lau C, Wallace KB, et al. Perfluoroalkyl acids–induced liver steatosis: effects on genes controlling lipid homeostasis. Toxicol. 2017;378:37–52. https://doi.org/10.1016/j.tox.2016.12.007
  16. 16. Ngo HT, Hetland RB, Sabaredzovic A, Haug LS, Steffensen IL. In utero exposure to perfluorooctanoate or perfluorooctane sulfonate did not increase body weight or intestinal tumorigenesis in multiple intestinal neoplasia mice. Environ Res. 2014;132:251–63. https://doi.org/10.1016/j.envres.2014.03.033
  17. 17. Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv Nutr. 2014;5(4):404–17. https://doi.org/10.3945/an.113.005603
  18. 18. Huang T, Chen X, Chen D, Yu B, He J, Yan H, et al. Eugenol promotes appetite through TRP channels mediated CaMKK2/AMPK signalling pathway. Phytother Res. 2023;37(7):2759–68. https://doi.org/10.1002/ptr.7768
  19. 19. Al–Harbi MS. Hepatoprotective effect and antioxidant capacity of naringenin on arsenic–induced liver injury in rats. Int J Pharm Pharm Sci. 2016;8(4):103–8.
  20. 20. Kumar A, Siddiqi NJ, Alrashood ST, Khan HA, Dubey A, Sharma B. Protective effect of eugenol on hepatic inflammation and oxidative stress induced by cadmium in male rats. Biomed Pharmacother. 2021;139:111588. https://doi.org/10.1016/j.biopha.2021.111588
  21. 21. Al–Okbi SY, Mohamed DA, Hamed TE, Edris AE. Protective effect of clove oil and eugenol microemulsions on fatty liver and dyslipidemia as components of metabolic syndrome. J Med Food. 2014;17(7):764–71. https://doi.org/10.1089/jmf.2013.0033
  22. 22. Goldwasser J, Cohen PY, Yang E, Balaguer P, Yarmush ML, Nahmias Y. Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: role of PPARα, PPARγ and LXRα. PLoS One. 2010;5(8):e12399. https://doi.org/10.1371/journal.pone.0012399
  23. 23. Ito M, Murakami K, Yoshino M. Antioxidant action of eugenol compounds: role of metal ion in the inhibition of lipid peroxidation. Food Chem Toxicol. 2005;43(3):461–6. https://doi.org/10.1016/j.fct.2004.11.019
  24. 24. Jayaraman J, Veerappan M, Namasivayam N. Potential beneficial effect of naringenin on lipid peroxidation and antioxidant status in rats with ethanol–induced hepatotoxicity. J Pharm Pharmacol. 2009;61(10):1383–90. https://doi.org/10.1211/jpp.61.10.0016
  25. 25. Abd El Motteleb DM, Selim SA, Mohamed AM. Differential effects of eugenol against hepatic inflammation and overall damage induced by ischemia/reperfusion injury. J Immunotoxicol. 2014;11(3):238–45. https://doi.org/10.3109/1547691X.2013.832444
  26. 26. Khaled SS, Soliman HA, Abdel–Gabbar M, Ahmed NA, El–Nahass ES, Ahmed OM. Naringin and naringenin counteract Taxol–induced liver injury in Wistar rats via suppression of oxidative stress, apoptosis and inflammation. Environ Sci Pollut Res. 2023;30(39):90892–905. https://doi.org/10.1007/s11356–023–28454–4
  27. 27. Eleleemy M, Amin BH, Nasr M, Sammour OA. A succinct review on the therapeutic potential and delivery systems of eugenol. Arch Pharm Sci Ain Shams Univ. 2020;4(2):290–311. https://doi.org/10.21608/aps.2021.50268.1047
  28. 28. Dayarathne LA. Anti-adipogenic and anti-diabetic effects of flavonoids. MSc [thesis]. Jeju: Jeju National University; 2021. https://dcoll.jejunu.ac.kr/common/orgView/000000010319
  29. 29. Lee Y, Nakano A, Nakamura S, Sakai K, Tanaka M, Sanematsu K, et al. In vitro and in silico characterisation of adiponectin–receptor agonist dipeptides. NPJ Sci Food. 2021;5(1):29. https://doi.org/10.1038/s41538-021-00114-2
  30. 30. Lu Y, Li DH, Xu JM, Zhou S. Role of naringin in the treatment of atherosclerosis. Front Pharmacol. 2024;15:1451445. https://doi.org/10.3389/fphar.2024.1451445
  31. 31. Pan T, Lee YM, Takimoto E, Ueda K, Liu PY, Shen HH. Inhibitory effects of naringenin on estrogen deficiency–induced obesity via regulation of mitochondrial dynamics and AMPK activation associated with white adipose tissue browning. Life Sci. 2024;340:122453. https://doi.org/10.1016/j.lfs.2024.122453
  32. 32. Jiang Y, Feng C, Shi Y, Kou X, Le G. Eugenol improves high-fat diet/streptomycin-induced type 2 diabetes mellitus mice muscle dysfunction by alleviating inflammation and increasing muscle glucose uptake. Front Nutr. 2022;9:1039753. https://doi.org/10.3389/fnut.2022.1039753
  33. 33. López–Almada G, Domínguez–Avila JA, Robles–Sánchez RM, Arauz–Cabrera J, Martínez–Coronilla G, González–Aguilar GA, et al. Naringenin decreases retroperitoneal adiposity and improves metabolic parameters in a rat model of Western diet–induced obesity. Metabolites. 2025;15(2):109. https://doi.org/10.3390/metabo15020109

Downloads

Download data is not yet available.