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Plant Science Today (PST)

Research Articles

Early Access

Subacute oral toxicity study of sesamol in Wistar albino rats

DOI
https://doi.org/10.14719/pst.11982
Submitted
25 September 2025
Published
22-04-2026

Abstract

Sesamol, a natural phenolic compound predominantly found in sesame oil, has attracted considerable research interest for its potent antioxidant activity and additional anti-inflammatory and anticancer effects, positioning it as a promising candidate for preventing and managing oxidative stress-related conditions and other therapeutic applications. The present study was undertaken to evaluate the subacute oral toxicity of sesamol in Wistar albino rats, thereby establishing its safety profile under repeated exposure. Following Organisation for Economic Co-operation and Development (OECD) guideline 407, the rats were administered daily with oral doses of  sesamol at doses of 26 mg/kg, 130 mg/kg and 650 mg/kg for 28 days, with inclusion of satellite groups to evaluate the reversibility of potential toxic effects. Haematological, biochemical, organ weight, clinical signs, feed, water intake and histopathological parameters were observed throughout the study. High-dose treated animals showed increased water intake. Biochemical studies showed elevation in alanine aminotransferase (ALT) in the high-dose treated group and satellite groups showed mild hepatic injury, while cholesterol and creatinine remained normal. Haematological studies showed reduced haemoglobin in the satellite high-dose treated group and decreased lymphocytes and monocytes in medium and high-dose treated groups, indicating possible myelosuppression. Liver histology revealed minimal dose-dependent steatosis at 130 mg/kg, mild at 650 mg/kg and partial recovery in satellite groups. No lesions were observed in the brain, kidney, heart, reproductive organs, or other tissues. In silico docking studies revealed that sesamol showed binding affinity to CYP1A2 (-6.5 kcal/mol) and CYP3A4 (-5.9 kcal/mol), suggesting possible interaction with drug-metabolising enzymes contributing to hepatotoxicity at higher doses. Sesamol was well tolerated at low and medium doses (26 and 130 mg/kg) without observed adverse effects, while the high dose (650 mg/kg) induced mild hepatotoxic and haematological changes. The no observed adverse effect level (NOAEL), lowest observed adverse effect level (LOAEL) and maximum tolerated dose (MTD) were determined as 130, 650 and 650 mg/kg per day respectively. These findings supported the safe use of sesamol at appropriate doses while emphasising the need for further evaluation of chronic toxicity, genotoxicity and mechanisms of toxicity.

 

References

  1. 1. Wei P, Zhao F, Wang Z, Wang Q, Chai X, Hou G, et al. Sesame (Sesamum indicum L.): A comprehensive review of nutritional value, phytochemical composition, health benefits, development of food and industrial applications. Nutrients. 2022;14:4079–89. https://doi.org/10.3390/nu14194079
  2. 2. Ley SH, Hamdy O, Mohan V, Hu FB. Prevention and management of type 2 diabetes: dietary components and nutritional strategies. Lancet. 2014;383:1999–2007. https://doi.org/10.1016/S0140-6736(14)60613-9
  3. 3. Bigoniya P, Nishad R, Singh S. Preventive effect of sesame seed cake on hyperglycemia and obesity against high fructose-diet induced type 2 diabetes in rats. Food Chem. 2012;133:1355–61. https://doi.org/10.1016/j.foodchem.2012.01.112
  4. 4. Prasad NMN, Sanjay KR, Prasad DS, Vijay N, Kothari R, Nanjunda Swamy S. A review on nutritional and nutraceutical properties of sesame. J Nutr Food Sci. 2012;2:1–6. https://doi.org/10.4172/2155-9600.1000127
  5. 5. Sowmya M, Jeyarani T, Jyotsna R, Indrani D. Effect of replacement of fat with sesame oil and additives on rheological, microstructural, quality characteristics and fatty acid profile of cakes. Food Hydrocoll. 2009;23:1827–36. https://doi.org/10.1016/j.foodhyd.2009.02.008
  6. 6. Sidharthan A. Therapeutic effect of sesamol and daidzein in letrozole-induced polycystic ovarian syndrome in Wistar rats [MVSc thesis]. Pookode: Kerala Veterinary and Animal Sciences University; 2024. 101 p.
  7. 7. Suvarna SK, Layton C, Bancroft JD. Bancroft’s theory and practice of histologic techniques. 8th ed. Philadelphia: Churchill Livingstone, Elsevier; 2018. 557 p.
  8. 8. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem. 2010;31(2):455–61. https://doi.org/10.1002/jcc.21334
  9. 9. Khan S, Begum N, Moin S, Shabeer J. Evaluation of sesamol-induced histopathological, biochemical, haematological and genotoxicological effects in mice. Toxicol Rep. 2016;3:788–97. https://doi.org/10.1016/j.toxrep.2016.03.005
  10. 10. Sewell F, Corvaro M, Andrus A, Burke J, Daston G, Delaney B, et al. Recommendations on dose level selection for repeat dose toxicity studies. Arch Toxicol. 2022;96(7):1921–34. https://doi.org/10.1007/s00204-022-03293-3
  11. 11. Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology. 2008;245(3):194–205. https://doi.org/10.1016/j.tox.2007.11.021
  12. 12. Liu Z, Que S, Xu J, Peng T. Alanine aminotransferase: an old biomarker and a new concept. Int J Med Sci. 2014;11(9):925–35. https://doi.org/10.7150/ijms.8951
  13. 13. Ramaiah L, Hinrichs MJ, Skuba EV, Iverson WO, Ennulat D. Interpreting and integrating clinical and anatomic pathology results: pulling it all together. Toxicol Pathol. 2017;45(1):223–37. https://doi.org/10.1177/0192623316677068
  14. 14. Begriche K, Massart J, Robin MA, Borgne-Sanchez A, Fromenty B. Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. J Hepatol. 2011;54(4):773–94. https://doi.org/10.1016/j.jhep.2010.11.006
  15. 15. Amacher DE, Chalasani N. Drug-induced hepatic steatosis. Semin Liver Dis. 2014;34(2):205–14. https://doi.org/10.1055/s-0034-1375960
  16. 16. Dash A, Figler RA, Sanyal AJ, Wamhoff BR. Drug-induced steatohepatitis. Expert Opin Drug Metab Toxicol. 2017;13(2):193–204. https://doi.org/10.1080/17425255.2017.1246534
  17. 17. Satapathy SK, Kuwajima V, Nadelson J, Atiq O, Sanyal AJ. Drug-induced fatty liver disease: an overview of pathogenesis and management. Ann Hepatol. 2015;14(6):789–806. https://doi.org/10.5604/16652681.1171749
  18. 18. Nakajima M, Suzuki M, Yamaji R, Takashina H, Shimada N, Yamazaki H, et al. Isoform selective inhibition and inactivation of human cytochrome P450s by methylenedioxyphenyl compounds. Xenobiotica. 1999;29(12):1191–202. https://doi.org/10.1080/004982599237877
  19. 19. Murray M. Mechanisms of inhibitory and regulatory effects of methylenedioxyphenyl compounds on cytochrome P450-dependent drug oxidation. Curr Drug Metab. 2000;1(1):67–84. https://doi.org/10.2174/1389200003339270
  20. 20. Takakusa H, Wahlin MD, Zhao C, Nelson SD, Moretto N, Dorato MA, et al. Metabolic intermediate complex formation of human cytochrome P450 3A4 by lapatinib. Drug Metab Dispos. 2011;39(6):1022–30. https://doi.org/10.1124/dmd.110.037531
  21. 21. Masubuchi Y, Takahashi C, Gendo R. Time-dependent inhibition of CYP1A2 by stiripentol and structurally related methylenedioxyphenyl compounds via metabolic intermediate complex formation. Drug Metab Dispos. 2024;52(1):DMD-AR-2023-001511. https://doi.org/10.1124/dmd.123.001511
  22. 22. Ioannides C, Delaforge M, Parke DV. Safrole: its metabolism, carcinogenicity and interactions with cytochrome P-450. Food Cosmet Toxicol. 1981;19(5):657–66. https://doi.org/10.1016/0015-6264(81)90518-6
  23. 23. Majdalawieh AF, Eltayeb AE, Abu-Yousef IA, Yousef SM. Hypolipidemic and anti-atherogenic effects of sesamol and possible mechanisms of action: a comprehensive review. Molecules. 2023;28(8):3567. https://doi.org/10.3390/molecules28083567
  24. 24. Abu-Elfotuh K, Selim HMRM, Riad OKM, Hamdan AM, Hassanin SO, Sharif AF, et al. The protective effects of sesamol and/or the probiotic Lactobacillus rhamnosus against aluminium chloride-induced neurotoxicity and hepatotoxicity in rats. Front Pharmacol. 2023;14:1208252. https://doi.org/10.3389/fphar.2023.1208252
  25. 25. Bankir L, Bichet DG, Morgenthaler NG. Vasopressin: physiology, assessment and osmosensation. J Intern Med. 2017;282(4):284–97. https://doi.org/10.1111/joim.12645
  26. 26. Dorato MA, Engelhardt JA. The no-observed-adverse-effect-level in drug safety evaluations: use, issues and definition(s). Regul Toxicol Pharmacol. 2005;42(3):265–74. https://doi.org/10.1016/j.yrtph.2005.05.004
  27. 27. Filipsson AF, Sand S, Nilsson J, Victorin K. The benchmark dose method-review of available models and recommendations for application in health risk assessment. Crit Rev Toxicol. 2003;33(5):505–42. https://doi.org/10.1080/10408440390242360
  28. 28. Buckley LA, Dorato MA. High dose selection in general toxicity studies for drug development: a pharmaceutical industry perspective. Regul Toxicol Pharmacol. 2009;54(3):301–7. https://doi.org/10.1016/j.yrtph.2009.05.015

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