ALPHA-LIPOIC ACID AND VITAMIN E COMBINATION ATTENUATES THIOACETAMIDE-INDUCED LIVER INJURY IN RATS
DOI:
https://doi.org/10.21010/Ajidv20i2S.4%20%20%20%20%20Keywords:
Thioacetamide; Alpha-Lipoic Acid; Hepatotoxicity; Histopathology; Oxidative Stress; Vitamin E.Abstract
Background: Thioacetamide (TAA) is a potent hepatotoxic agent that induces oxidative stress, inflammation, and severe hepatic injury. This study evaluated the hepatoprotective effect of Alpha-Lipoic Acid (ALA) and Vitamin E, alone and in combination, against TAA-induced liver damage in male albino rats.
Materials and Methods: Thirty-five adult male albino rats were randomly allocated into five groups (n = 7): control, TAA, Vitamin E + TAA, ALA + TAA, and Vitamin E + ALA + TAA. TAA (200 mg/kg) was administered intraperitoneally twice weekly, and Vitamin E and/or ALA (100 mg/kg each) were administered orally once daily for a total treatment period of 4 weeks. Serum ALT, AST, TNF-α, IL-10 and CK-18, and hepatic MDA and GSH levels were measured, and liver sections were evaluated histopathologically.
Results: TAA administration significantly increased serum ALT, AST, CK-18, MDA and TNF-α, and significantly decreased GSH and IL-10, compared with control (P<0.05), together with marked histopathological injury. Treatment with Vitamin E or ALA significantly improved all parameters relative to the TAA group, and combined Vitamin E + ALA treatment produced the greatest improvement, with near-normal hepatic architecture.
Conclusion: Combined administration of Alpha-Lipoic Acid and Vitamin E provided greater hepatoprotection than either agent alone against TAA-induced hepatotoxicity, reducing oxidative stress and inflammation and preserving hepatocellular structure and function.
References
Abd El-Hameed, S., Ibrahim, I., Awadin, W. and El-Shaieb, A. (2025). Pathological and Ultrastructural Study on the Chronic Liver Damage Induced by Thioacetamide in Male Rats. Egyptian Journal of Veterinary Sciences, 56, 2197-2205.
Abdelhalim, M. A. K., Qaid, H. A., Al-Mohy, Y. H. and Ghannam, M. M. (2020). The protective roles of vitamin E and α-lipoic acid against nephrotoxicity, lipid peroxidation, and inflammatory damage induced by gold nanoparticles. International Journal of Nanomedicine, 729-734.
Abdelrahman, R. S. and Abdelmageed, M. E. (2024). Hepatoprotective effects of the xanthine oxidase inhibitor Febuxostat against thioacetamide-induced liver injury in rats: The role of the Nrf2/HO-1 and TLR4/NF-κB pathways. Food and Chemical Toxicology, 194, 115087.
Aboubakr, M., et al. (2023). Protective effects of N-acetylcysteine and vitamin E against acrylamide-induced neurotoxicity in rats. Pakistan Veterinary Journal, 43, 262-268.
Ahmed, R. F., et al. (2025). Phenolic-rich extracts of Teucrium oliverianum confer protection against thioacetamide-induced liver fibrosis in rats: Insights from metabolomics, biochemical and histopathological analysis. PLOS ONE, 20, e0330595.
Al-Medhtiy, M. H., Jabbar, A. A., Shareef, S. H., Ibrahim, I. A. A., Alzahrani, A. R. and Abdulla, M. A. (2022). Histopathological evaluation of Annona muricata in TAA-induced liver injury in rats. Processes, 10, 1613.
Alamri, Z. Z. (2024). Protective and therapeutic effects of apigenin on thioacetamide-induced hepatotoxicity in male rats: physiological and morphological study. Egyptian Liver Journal, 14, 15.
Albadrani, G. M., et al. (2024). Effects of alfa lipoic acid and coenzyme Q10 treatment on AFB1-induced oxidative, inflammatory, and DNA damages in rats. Toxicon, 249, 108083.
Alkreathy, H. M. and Esmat, A. (2022). Lycorine ameliorates thioacetamide-induced hepatic fibrosis in rats: emphasis on antioxidant, anti-inflammatory, and STAT3 inhibition effects. Pharmaceuticals, 15, 369.
Ali, L. H., Rajab, S. H., & Saleh, E. N. (2024). Protective role of vitamin B6 on some histological changes in the liver and kidneys and measure some indicators of oxidation balance in male rats. Cellular and Molecular Biology, 70(11), 160-165.
Badawy, S. S., Mashaly, M. M., Abdel-Aziz, A. and Madkour, M. M. (2025). The ameliorative effects of metformin and taurine against thioacetamide hepatotoxicity in rats. Toxicology Research, 14, tfaf076.
Bancroft, J. D. (2013). Histochemical Techniques. Butterworth-Heinemann.
Bratoeva, K., et al. (2018). Association between serum CK-18 levels and the degree of liver damage in fructose-induced metabolic syndrome. Metabolic Syndrome and Related Disorders, 16, 350-357.
Chee, N. M. Z., Sinnanaidu, R. P. and Chan, W. K. (2024). Vitamin E improves serum markers and histology in adults with metabolic dysfunction-associated steatotic liver disease: Systematic review and meta-analysis. Journal of Gastroenterology and Hepatology, 39, 2545-2554.
Chen, J., et al. (2022). Interleukin 10 inhibits oxidative stress-induced autophagosome formation in hepatic stellate cells by activating the mTOR-STAT3 pathway. Experimental Cell Research, 411, 113001.
Dawood, R. W., Hameed, A. T., & Sayer, S. H. (2022). The protective effect of the alcoholic extract Lactuca serriola on some physiological parameters in the liver in white mice induced with Benzo (a) pyrene. Journal of Pharmaceutical Negative Results, 13(4), 765-771.
Ebaid, H., Bashandy, S. A., Morsy, F. A., Al-Tamimi, J., Hassan, I. and Alhazza, I. M. (2023). Protective effect of gallic acid against thioacetamide-induced metabolic dysfunction of lipids in hepatic and renal toxicity. Journal of King Saud University-Science, 35, 102531.
El-Alkamy, A. M. T., Tayel, S. M., Safwat, M., Abdallah, D. M. and Nabil, N. M. (2023). The protective effect of quercetin on thioacetamide-induced liver cirrhosis in adult male albino rats. Egyptian Journal of Histology, 46, 561-574.
El-Hameed, S. A., Ibrahim, I., Awadin, W. and El-Shaieb, A. (2023). Thioacetamide: Definition, Exposure, Hepatic and Renal Toxicity. Mansoura Veterinary Medical Journal, 24, 3.
El-Mancy, E. M., et al. (2022). α-Lipoic acid protects against cyclosporine A-induced hepatic toxicity in rats: effect on oxidative stress, inflammation, and apoptosis. Toxics, 10, 442.
Elsayed, F. I., Gad, F. A. and Ahmed, O. A. S. (2022). Biochemical, histological and immunohistochemical studies on the efficacy of garlic oil against thioacetamide-induced hepatotoxicity in rats. Benha Veterinary Medical Journal, 42, 88-93.
Ezhilarasan, D. (2023). Molecular mechanisms in thioacetamide-induced acute and chronic liver injury models. Environmental Toxicology and Pharmacology, 99, 104093.
Gezer, A., Laloglu, A. and Bölükbaş, M. K. (2023). Protective effects of alpha lipoic acid against ionizing radiation-induced hepatotoxicity in rats. The Eurasian Journal of Medicine, 55, 104.
Griffith, O. W. (1980). Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Analytical Biochemistry, 106, 207-212.
Jamali, H., et al. (2026). The effects of co-administration of lithium and vitamin E on hepatic oxidative status in aged male and female rats: Biochemical and histomorphological evaluations. Biological Trace Element Research, 204, 987-1000.
Kaçar, A. K., Ertik, O., Coşkun, Z. M., Bolkent, S., Yanardağ, R. and Bolkent, Ş. (2023). The combined ameliorative effects of α-lipoic acid, selenium, and vitamin E on the livers of STZ-diabetic mice. İstanbul Journal of Pharmacy, 53, 199-210.
Kalra, A., Yetiskul, E., Wehrle, C. J. and Tuma, F. (2023). Physiology, Liver. In StatPearls [Internet]. StatPearls Publishing.
Kaye, A. D., et al. (2025). Vitamin E (α-tocopherol): emerging clinical role and adverse risks of supplementation in adults. Cureus, 17.
Khan, I. U., Ali, S., Shahid, A., Rasheed, M. R., Mehmood, M. S. and Khan, B. U. (2025). Comparative Study of the Protective Effects of Alpha-Lipoic Acid and Alpha-Tocopherol on Isoniazid-Induced Hepatitis in Mice. Portal, 9, 30.
Krishna, S. B. N. (2025). Alpha-Lipoic Acid (ALA) as a Potential Antidiabetic Agent. In Organic Acids in Diabetes (pp. 35-53). CRC Press.
Megahed, A., et al. (2023). Vitamin D ameliorates the hepatic oxidative damage and fibrotic effect caused by thioacetamide in rats. Biomedicines, 11, 424.
Mohammed, O. A. (2023). Alogliptin exhibits multifaceted effects in thioacetamide-insulted rats: a novel approach to combating hepatic inflammation and fibrogenesis. Pathology - Research and Practice, 250, 154833.
Mooli, R. G. R., Mukhi, D. and Ramakrishnan, S. K. (2022). Oxidative stress and redox signaling in the pathophysiology of liver diseases. Comprehensive Physiology, 12, 3167-3192.
Nuhoğlu, H. (2024). Chemically and pharmacologically induced liver toxicity models in experimental animals and observed changes. Rats, 2, 51-62.
Ohkawa, H., Ohishi, N. and Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95, 351-358.
Reitman, S. and Frankel, S. (1957). A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology, 28, 56-63.
Shareef, S. H., Ibrahim, I. A. A., Alzahrani, A. R., Al-Medhtiy, M. H. and Abdulla, M. A. (2022). Hepatoprotective effects of methanolic extract of green tea against Thioacetamide-Induced liver injury in Sprague Dawley rats. Saudi Journal of Biological Sciences, 29, 564-573.
Tang, S.-P., Mao, X.-L., Chen, Y.-H., Yan, L.-L., Ye, L.-P. and Li, S.-W. (2022). Reactive oxygen species induce fatty liver and ischemia-reperfusion injury by promoting inflammation and cell death. Frontiers in Immunology, 13, 870239.
Vargas-Pozada, E. E., et al. (2023). The antioxidant and anti-inflammatory activities of caffeine effectively attenuate nonalcoholic steatohepatitis and thioacetamide-induced hepatic injury in male rats. Canadian Journal of Physiology and Pharmacology, 101, 147-159.
Yunusoğlu, O. and Koyuncu, E. (2025). Alpha-lipoic acid in pharmaceutical development: A comprehensive review of its therapeutic potential and molecular mechanisms. Prospects in Pharmaceutical Sciences, 23, 67-86.
Zhang, X., Li, J., Jiang, L., Deng, Y., Wei, L. and Li, X. (2024). Serum Cytokeratin-18 levels as a prognostic biomarker in advanced liver disease: a comprehensive meta-analysis. Clinical and Experimental Medicine, 24, 160.
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