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Assessment of Paracetamol Toxicity in The Presence of Sugar in Rat
Subject area: Biological & Medical Sciences · Area of research: Paracetamol Toxicity
DOI: 10.64388/IREV10I3-1723028
Abstract
Paracetamol (PCM)–induced hepatotoxicity is a major cause of drug-related liver injury, while the role of dietary sugar in modulating this toxicity remains unclear. This study evaluated the dose-dependent effect of sugar on PCM-induced liver damage in rats. Hepatotoxicity was induced using paracetamol, followed by co-administration of sugar at 50% and 100% concentrations. Liver injury was assessed using body and relative liver weight, serum biochemical markers (ALT, AST, ALP), oxidative stress parameters, and histopathology. Paracetamol significantly increased relative liver weight (7.50 ± 0.35%) compared to normal controls (4.80 ± 0.20%) and elevated ALT (140.0 ± 4.5 U/L), AST (155.0 ± 6.4 U/L), and ALP (260.0 ± 8.0 U/L) levels (p < 0.001). Lipid peroxidation increased markedly, with MDA levels rising to 3.80 ± 0.25 nmol/mg protein versus 1.20 ± 0.15 nmol/mg protein in controls, alongside reduced antioxidant enzymes. Co-administration of 50% sugar partially attenuated PCM-induced toxicity, whereas 100% sugar aggravated oxidative stress (MDA: 4.50 ± 0.30 nmol/mg protein) and liver damage.These findings suggest that moderate sugar intake may offer limited hepatoprotection, while excessive sugar worsens PCM-induced liver injury.
Keywords
Paracetamol, Hepatotoxicity, Sugar, Oxidative stress
References
[1] Aebi, H. (1984). Catalase in vitro. Methods in Enzymology, 105, 121–126. Crossref
[2] Arifin, M., Jannah, W., Zakiyah, N., Meiliana, A., Barliana, M. I., & Lestari, K. (2026). Fructose diet–induced liver injury through oxidative stress: A systematic review of preclinical studies. Journal of Nutrition and Metabolism, 2026, Article 1644860. Crossref
[3] Baharuddin, B. (2024). The impact of fructose consumption on human health: Effects on obesity, hyperglycemia, diabetes, uric acid, and oxidative stress with a focus on the liver. Cureus, 16(9), e70095. Crossref
[4] Bancroft, J. D., & Gamble, M. (2008). Theory and Practice of Histological Techniques (6th ed.). Churchill Livingstone/Elsevier.
[5] Basciano, H., Federico, L., & Adeli, K. (2005). Fructose, insulin resistance, and metabolic dyslipidemia. Nutrition & Metabolism, 2, 5. Crossref
[6] Chiu, S., Sievenpiper, J. L., de Souza, R. J., Cozma, A. I., Mirrahimi, A., Carleton, A. J., Ha, V., Di Buono, M., Jenkins, A. L., Leiter, L. A., Wolever, T. M. S., Don-Wauchope, A. C., Beyene, J., Kendall, C. W. C., & Jenkins, D. J. A. (2014). Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of controlled feeding trials. European Journal of Clinical Nutrition, 68(4), 416–423. Crossref
[7] Ellman, G. L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82(1), 70–77. Crossref
[8] Federico, A., Rosato, V., Masarone, M., Torre, P., Dallio, M., Romeo, M., & Persico, M. (2021). The role of fructose in non-alcoholic steatohepatitis: Old relationship and new insights. Nutrients, 13(4), 1314. Crossref
[9] James, L. P., Mayeux, P. R., & Hinson, J. A. (2003). Acetaminophen-induced hepatotoxicity. Drug Metabolism and Disposition, 31(12), 1499–1506. Crossref
[10] Jegatheesan, P., & De Bandt, J. P. (2017). Fructose and NAFLD: The multifaceted aspects of fructose metabolism. Nutrients, 9(3), 230. Crossref
[11] Jollow, D. J., Mitchell, J. R., Potter, W. Z., Davis, D. C., Gillette, J. R., & Brodie, B. B. (1973). Acetaminophen-induced hepatic necrosis. II. Role of covalent binding in vivo. Journal of Pharmacology and Experimental Therapeutics, 187(1), 195–202.
[12] Kakkar, P., Das, B., & Viswanathan, P. N. (1984). A modified spectrophotometric assay of superoxide dismutase. Indian Journal of Biochemistry and Biophysics, 21(2), 130–132.
[13] Kind, P. R. N., & King, E. J. (1954). Estimation of plasma phosphatase by determination of hydrolysed phenol with amino-antipyrine. Journal of Clinical Pathology, 7(4), 322–326. Crossref
[14] Larson, A. M., Polson, J., Fontana, R. J., Davern, T. J., Lalani, E., Hynan, L. S., Reisch, J. S., Schiødt, F. V., Ostapowicz, G., Shakil, A. O., & Lee, W. M. (2005). Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study. Hepatology, 42(6), 1364–1372. Crossref
[15] Lodge, M., Dykes, R., & Kennedy, A. (2024). Regulation of fructose metabolism in nonalcoholic fatty liver disease. Biomolecules, 14(7), 845. Crossref
[16] Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1), 265–275. Crossref
[17] Mahmood, N. D., Mamat, S. S., Kamisan, F. H., Yahya, F., Kamarolzaman, M. F. F., Nasir, N., Mohtarrudin, N., Md Tohid, S. F., & Zakaria, Z. A. (2014). Amelioration of paracetamol-induced hepatotoxicity in rat by the administration of methanol extract of Muntingia calabura L. leaves. BioMed Research International, 2014, 695678. Crossref
[18] Mai, B. H., & Yan, L. J. (2019). The negative and detrimental effects of high fructose on the liver, with special reference to metabolic disorders. Diabetes, Metabolic Syndrome and Obesity, 12, 821–826. Crossref
[19] Mitchell, J. R., Jollow, D. J., Potter, W. Z., Gillette, J. R., & Brodie, B. B. (1973). Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. Journal of Pharmacology and Experimental Therapeutics, 187(1), 211–217.
[20] Muriel, P., López-Sánchez, P., & Ramos-Tovar, E. (2021). Fructose and the liver. International Journal of Molecular Sciences, 22(13), 6969. Crossref
[21] Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351–358. Crossref
[22] Organisation for Economic Co-operation and Development. (2002). Test No. 423: Acute Oral Toxicity – Acute Toxic Class Method. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing. Crossref
[23] Ramachandran, A., & Jaeschke, H. (2017). Mechanisms of acetaminophen hepatotoxicity and their translation to the human pathophysiology. Journal of Clinical and Translational Research, 3(Suppl. 1), 157–169. Crossref
[24] Ramachandran, R., & Kakar, S. (2009). Histological patterns in drug-induced liver disease. Journal of Clinical Pathology, 62(6), 481–492. Crossref
[25] Reitman, S., & Frankel, S. (1957). A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology, 28(1), 56–63. Crossref
[26] Rumack, B. H., & Matthew, H. (1975). Acetaminophen poisoning and toxicity. Pediatrics, 55(6), 871–876. Crossref
[27] Senthilkumar, R., Chandran, R., & Parimelazhagan, T. (2014). Hepatoprotective effect of Rhodiola imbricata rhizome against paracetamol-induced liver toxicity in rats. Saudi Journal of Biological Sciences, 21(5), 409–416. Crossref
[28] World Health Organization. (2015). Guideline: Sugars Intake for Adults and Children. WHO Press.
[29] Yahya, F., Mamat, S. S., Kamarolzaman, M. F. F., Seyedan, A. A., Jakius, K. F., Mahmood, N. D., Shahril, M. S., Suhaili, Z., Mohtarrudin, N., Susanti, D., Somchit, M. N., Teh, L. K., Salleh, M. Z., & Zakaria, Z. A. (2013). Hepatoprotective activity of methanolic extract of Bauhinia purpurea leaves against paracetamol-induced hepatic damage in rats. Evidence-Based Complementary and Alternative Medicine, 2013, 636580. Crossref
How to cite this paper
@article{1723028,
author = {Deep Shita Singh},
title = {Assessment of Paracetamol Toxicity in The Presence of Sugar in Rat},
journal = {Iconic Research And Engineering Journals},
year = {2026},
volume = {10},
number = {3},
pages = {1182-1195},
issn = {2456-8880},
url = {https://www.irejournals.com/formatedpaper/1723028.pdf},
abstract = {Paracetamol (PCM)–induced hepatotoxicity is a major cause of drug-related liver injury, while the role of dietary sugar in modulating this toxicity remains unclear. This study evaluated the dose-dependent effect of sugar on PCM-induced liver damage in rats. Hepatotoxicity was induced using paracetamol, followed by co-administration of sugar at 50% and 100% concentrations. Liver injury was assessed using body and relative liver weight, serum biochemical markers (ALT, AST, ALP), oxidative stress parameters, and histopathology. Paracetamol significantly increased relative liver weight (7.50 ± 0.35%) compared to normal controls (4.80 ± 0.20%) and elevated ALT (140.0 ± 4.5 U/L), AST (155.0 ± 6.4 U/L), and ALP (260.0 ± 8.0 U/L) levels (p < 0.001). Lipid peroxidation increased markedly, with MDA levels rising to 3.80 ± 0.25 nmol/mg protein versus 1.20 ± 0.15 nmol/mg protein in controls, alongside reduced antioxidant enzymes. Co-administration of 50% sugar partially attenuated PCM-induced toxicity, whereas 100% sugar aggravated oxidative stress (MDA: 4.50 ± 0.30 nmol/mg protein) and liver damage.These findings suggest that moderate sugar intake may offer limited hepatoprotection, while excessive sugar worsens PCM-induced liver injury.},
keywords = {Paracetamol, Hepatotoxicity, Sugar, Oxidative stress},
month = {September},
doi = {https://doi.org/10.64388/IREV10I3-1723028}
}