Ameliorative effects of eugenol on lead-induced mitochondrial dysfunction and hepatic inflammation in male Wistar rats
Article Main
Abstract
Lead is a persistent environmental toxicant known to induce severe hepatic damage primarily through oxidative stress, mitochondrial impairment, and inflammatory responses. Eugenol, a naturally occurring phenolic compound, has emerged as a promising bioactive agent due to its antioxidant and anti-inflammatory properties. Its potential to protect against toxin-induced hepatic injury, particularly through modulation of mitochondrial function and inflammatory pathways, remains of considerable interest. The present study evaluated the hepatoprotective efficacy of eugenol against lead-induced hepatic toxicity in male Wistar rats. Animals were divided into four groups: control, eugenol (5 mg/kg), lead (30 mg/kg), and eugenol + lead co-treatment. Mitochondrial enzyme activities, semi-quantitative gene expression of inflammatory mediators, and ultrastructural changes were assessed. Eugenol administration significantly mitigated lead-induced mitochondrial dysfunction, as evidenced by a 47%, 31%, and 30% restoration of complex I, II, and IV activities, respectively. Furthermore, eugenol attenuated the transcriptional upregulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-12) and altered NF-κB transcription, suggesting its potential anti-inflammatory effects. Ultrastructural analysis demonstrated preservation of mitochondrial integrity and reduced nuclear chromatin condensation in hepatocytes following eugenol co-treatment. These findings highlight eugenol's capacity to modulate mitochondrial function and inflammatory gene expression, thereby conferring protection against hepatic injury. The study underscores the therapeutic potential of eugenol as a natural agent for mitigating toxin-induced liver damage and supports its further exploration as a hepatoprotective strategy.
Article Details
Article Details
Keywords
Eugenol, Hepatoprotection, Inflammation, Lead toxicity, Mitochondrial dysfunction
References
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Bai, T., Li, J., Murtaza, A., Iqbal, A., Zhu, L., Zhang, J., Zhang, B., Xu, X., Pan, S. & Hu, W. (2022). Scavenging of ROS after eugenol treatment as mechanism of slowing down membrane lipid metabolism to maintain the surface color of fresh-cut yam. Food and Bioprocess Technology, 15(8), 1821–1835. https://doi.org/10.1007/s11947-022-02833-0
Barhoma, R. A. E. (2018). The role of eugenol in the prevention of chromium-induced acute kidney injury in male albino rats. Alexandria Journal of Medicine, 54(4), 711–715. https://doi.org/10.1016/j.ajme.2018.05.006
Bhol, N. K., Bhanjadeo, M. M., Singh, A. K., Dash, U. C., Ojha, R. R., Majhi, S., Duttaroy, A. K. & Jena, A. B. (2024). The interplay between cytokines, inflammation, and antioxidants: mechanistic insights and therapeutic potentials of various antioxidants and anti-cytokine compounds. In Biomedicine and Pharmacotherapy, (178), 117-177. https://doi.org/10.1016/j.biopha.2024.
Binu, P., Priya, N., Abhilash, S., Radhakrishnan, ;, Vineetha, C. & Nair, H. (2018). Protective effects of eugenol against hepatotoxicity induced by arsenic trioxide: An antileukemic drug. Iranian Journal of Medical Sciences. 43 (3), 305-312.
Boskabady, M., Marefati, N., Farkhondeh, T., Shakeri, F., Farshbaf, A. & Boskabady, M. H. (2018). The effect of environmental lead exposure on human health and the contribution of inflammatory mechanisms, a review. Environment International, 120(2018), 404–420. https://doi.org/10.1016/j.envint.2018.08.013
Chen, P., Chen, F. & Zhou, B. (2018). Antioxidative, anti-inflammatory and anti-apoptotic effects of ellagic acid in liver and brain of rats treated by D-galactose. Scientific Reports, 8(1), 1465. https://doi.org/10.1038/s41598-018-19732-0
Chibowska, K., Baranowska-Bosiacka, I., Falkowska, A., Gutowska, I., Goschorska, M. & Chlubek, D. (2016). Effect of lead (Pb) on inflammatory processes in the brain. International Journal of Molecular Sciences, 17(12), 2140. https://doi.org/10.3390/ijms17122140
Chlubek, M. & Baranowska-Bosiacka, I. (2024). Selected functions and disorders of mitochondrial metabolism under lead exposure. Cells, 13(14), 1182. https://doi.org/10.3390/cells13141182
Damasceno, R. O. S., Pinheiro, J. L. S., Rodrigues, L. H. M., Gomes, R. C., Duarte, A. B. S., Emídio, J. J., Diniz, L. R. L. & de Sousa, D. P. (2024). Anti-inflammatory and antioxidant activities of eugenol: An Update. Pharmaceuticals, 17(11), 1505. https://doi.org/10.3390/ph17111505
Devi, S., Chauhan, S., Mannan, A. & Singh, T. G. (2024). Targeting cardiovascular risk factors with eugenol: an anti-inflammatory perspective. Inflammopharmacology, 32(1), 307–317. https://doi.org/10.1007/s10787-023-01392-w
Fouad, A. A. & Yacoubi, M. T. (2011). Mechanisms underlying the protective effect of eugenol in rats with acute doxorubicin cardiotoxicity. Archives of Pharmacal Research, 34(5), 821–828. https://doi.org/10.1007/s12272-011-0516-2
Ibrahim, I. A., Shalaby, A. A., Abd Elaziz, R. T. & Bahr, H. I. (2021). Chlorella vulgaris or Spirulina platensis mitigate lead acetate-induced testicular oxidative stress and apoptosis with regard to androgen receptor expression in rats. Environmental Science and Pollution Research, 28(29), 39126-39138. https://doi.org/10.1007/s11356-021-13411-w
Harshitha, P., Bose, K. & Dsouza, H. S. (2024). Influence of lead-induced toxicity on the inflammatory cytokines. Toxicology, 503(2024), 153771. https://doi.org/10.1016/j.tox.2024.153771
Hasanpuri, A., Bhardwaj, S., Singh, J., Sheoran, R. & Malik, V. (2026). Eugenol alleviating lead-induced hepatic toxicity in male Wistar rats by regulating endogenous antioxidants: histological, in vivo and in silico evidence. Research Journal of Biotechnology, 21(4), 250-260. https://doi.org/10.25303/214rjbt2500260
Jarrar, B. M. & Taib, N. T. (2012). Histological and histochemical alterations in the liver induced by lead chronic toxicity. Saudi Journal of Biological Sciences, 19(2), 203–210. https://doi.org/10.1016/j.sjbs.2011.12.005
Kaur, P., Radotra, B., Minz, R. W. & Gill, K. D. (2007). Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic dichlorvos (OP) exposure in rat brain. NeuroToxicology, 28(6), 1208–1219. https://doi.org/10.1016/j.neuro.2007.08.001
Kim, H. C., Jang, T. W., Chae, H. J., Choi, W. J., Ha, M. N., Ye, B. J., Kim, B. G., Jeon, M. J., Kim, S. Y. & Hong, Y. S. (2015). Evaluation and management of lead exposure. Annals of Occupational and Environmental Medicine, 27(1), 30. https://doi.org/10.1186/s40557-015-0085-9
Kumar, A., Siddiqi, N. J., Alrashood, S. T., Khan, H. A., Dubey, A. & Sharma, B. (2021). Protective effect of eugenol on hepatic inflammation and oxidative stress induced by cadmium in male rats. Biomedicine and Pharmacotherapy, 139(2021,) 111588. https://doi.org/10.1016/j.biopha.2021.111588
LOWRY, O. H., ROSEBROUGH, N. J., FARR, A. L. & RANDALL, R. J. (1951). Protein measurement with the folin phenol reagent. The Journal of Biological Chemistry, 193(1), 265–275. https://doi.org/10.1016/s0021-9258(19)52451-6
Lu, T. H., Su, C. C., Chen, Y. W., Yang, C. Y., Wu, C. C., Hung, D. Z., Chen, C. H., Cheng, P. W., Liu, S. H. & Huang, C. F. (2011). Arsenic induces pancreatic β-cell apoptosis via the oxidative stress-regulated mitochondria-dependent and endoplasmic reticulum stress-triggered signaling pathways. Toxicology Letters, 201(1), 15–26. https://doi.org/10.1016/j.toxlet.2010.11.019
Ma, L., Liu, J. Y., Dong, J. X., Xiao, Q., Zhao, J. & Jiang, F. L. (2017). Toxicity of Pb2+ on rat liver mitochondria induced by oxidative stress and mitochondrial permeability transition. Toxicology Research, 6(6), 822–830. https://doi.org/10.1039/c7tx00204a
Mani, M. S., Joshi, M. B., Shetty, R. R., DSouza, V. L., Swathi, M., Kabekkodu, S. P. & Dsouza, H. S. (2020). Lead exposure induces metabolic reprogramming in rat models. Toxicology Letters, 335, 11–27. https://doi.org/10.1016/j.toxlet.2020.09.010
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Ameliorative effects of eugenol on lead-induced mitochondrial dysfunction and hepatic inflammation in male Wistar rats. (2026). Journal of Applied and Natural Science, 18(2), 905-915. https://doi.org/10.31018/jans.v18i2.7584
