Acute Oral Toxicity Assessment of Rutinoside on Renal Histopathology in Wistar Rats

Authors

  • Rena Normasari Jember University
  • Yulia Mega Pratiwi Jember University

DOI:

https://doi.org/10.47134/ijhis.v3i3.79

Keywords:

Acute Oral Toxicity, Renal Histopathology, Rutinoside

Abstract

This study aimed to evaluate the acute oral toxicity of rutinoside by assessing renal histopathological changes in Wistar rats. Twelve Wistar rats (Rattus norvegicus), consisting of equal numbers of males and females and aged approximately three months, were randomly assigned to control and treatment groups. After an acclimatization period under standard laboratory conditions, the treatment group received a single oral dose of rutinoside (5000 mg/kg body weight) via gastric gavage in accordance with OECD Guideline 423, while the control group received the vehicle only. Animals were observed daily for 14 days for mortality, behavioral changes, and clinical signs of toxicity. At the end of the observation period, rats were euthanized, and both kidneys were collected for histopathological evaluation. Kidney tissues were fixed in 10% buffered formalin, processed, and stained with hematoxylin and eosin. Histological examination was performed at 400× magnification using a standardized scoring system, and statistical analysis was conducted using the Mann–Whitney U test. No mortality or treatment-related clinical signs were observed during the study period. Histopathological findings demonstrated no significant differences between the control and rutinoside-treated groups. Renal structures, including glomeruli and tubules, remained intact, with no evidence of degeneration, inflammation, or other pathological alterations. In conclusion, acute oral administration of rutinoside at a high dose did not induce renal toxicity in Wistar rats, suggesting a favorable acute safety profile. Further studies are required to evaluate the safety of rutinoside following repeated or long-term exposure.

References

[1] Ganeshpurkar and A. K. Saluja, “The pharmacological potential of rutin,” Saudi Pharm J, vol. 25, no. 2, pp. 149–164, 2017, doi: https://doi.org/10.1016/j.jsps.2016.04.025

[2] Gęgotek, P. Rybałtowska-Kawałko, and E. Skrzydlewska, “Rutin as a mediator of lipid metabolism and cellular signaling pathways interactions in fibroblasts altered by UVA and UVB radiation,” Oxidative Medicine and Cellular Longevity, 2017, p. 4721352, doi: https://doi.org/10.1155/2017/4721352

[3] R. Alhoshani, M. M. Hafez, S. Husain, A. M. Al-Sheikh, M. R. Alotaibi, S. S. Al Rejaie, M. A. Alshammari, M. M. Almutairi, and O. A. Al-Shabanah, “Protective effect of rutin supplementation against cisplatin-induced nephrotoxicity in rats,” BMC Nephrology, vol. 18, no. 1, p. 194, 2017, doi: https://doi.org/10.1186/s12882-017-0601-y

[4] S. Mecenas et al., “Rutin derivatives obtained by transesterification reactions catalyzed by Novozym 435: Antioxidant properties and absence of toxicity in mammalian cells,” PLoS One, vol. 13, no. 9, e0203159, 2018, doi: https://doi.org/10.1371/journal.pone.0203159

[5] D. D. Wisudanti, R. Normasari, and F. Herdiyana, “Nephroprotective effect of soy (Glycine Max (L.) Merr.) flour against diazinon-induced renal toxicity in rats,” Universa Medicina, vol. 39, no. 3, pp. 192–198, 2020, doi: https://doi.org/10.18051/UnivMed.2020.v39.192-198

[6] H. Hasnat et al., “Flavonoids: A treasure house of prospective pharmacological potentials,” Heliyon, vol. 10, no. 6, e27533, 2024, doi: https://doi.org/10.1016/j.heliyon.2024.e27533

[7] H. J. Lim et al., “Antioxidant and antineuroinflammatory mechanisms of kaempferol-3-O-β-d-glucuronate on lipopolysaccharide-stimulated BV2 microglial cells through the Nrf2/HO-1 signaling cascade and MAPK/NF-κB pathway,” ACS Omega, vol. 8, no. 7, pp. 6538–6549, 2023, doi: https://doi.org/10.1021/acsomega.2c06916

[8] H. K. Sandhar et al., “A review of phytochemistry and pharmacology of flavonoids,” Internationale Pharmaceutica Sciencia, 2011.

[9] J. Cvorovic, L. Ziberna, S. Fornasaro, F. Tramer, and S. Passamonti, “Bioavailability of flavonoids: The role of cell membrane transporters,” in Polyphenols: Mechanisms of Action in Human Health and Disease, pp. 295–319, 2018, doi: https://doi.org/10.1016/B978-0-12-813006-3.00022-2

[10] M. Jonsson et al., “Application of OECD Guideline 423 in assessing the acute oral toxicity of moniliformin,” Food and Chemical Toxicology, vol. 53, pp. 27–32, 2013, doi: https://doi.org/10.1016/j.fct.2012.11.023

[11] M.-R. Khajevand-Khazaei et al., “Rutin, a quercetin glycoside, alleviates acute endotoxemic kidney injury in C57BL/6 mice via suppression of inflammation and up-regulation of antioxidants and SIRT1,” European Journal of Pharmacology, vol. 833, pp. 307–313, 2018, doi: https://doi.org/10.1016/j.ejphar.2018.06.019

[12] OECD, The Organization of Economic Co-operation and Development Guidelines Test No. 423: Acute Oral Toxicity – Acute Toxic Class Method, OECD Guidelines for the Testing of Chemicals, Section 4, Feb. 2002, pp. 1–14.

[13] P. Jantrawut, R. Phongpradist, M. Muller, and H. Viernstein, “Enhancement of anti-inflammatory activity of polyphenolic flavonoid rutin by encapsulation,” Pak J Pharm Sci, vol. 30, no. 5, pp. 1521–1527, 2017.

[14] P. Thakur et al., “Unveiling the substantial role of rutin in the management of drug-induced nephropathy using network pharmacology and molecular docking,” International Immunopharmacology, vol. 146, p. 113911, 2024, doi: https://doi.org/10.1016/j.intimp.2024.113911

[15] R. Normasari, A. M. Jamila, and A. Purwandhono, “Evaluation of acute oral toxicity of flavonoid rutinoside on liver histopathology in Wistar rats,” Agromedicine and Medical Sciences, vol. 11, no. 1, pp. 39–42, 2025, doi: https://doi.org/10.19184/ams.v11i1.53712

[16] R. Normasari, B. Purwanto, and D. Tinduh, “Exploring rutinoside’s impact on inflammation in a rat knee OA model induced by monosodium iodoacetate (MIA),” Bali Medical Journal, vol. 13, no. 1, pp. 106–109, 2024a, doi: https://doi.org/10.15562/bmj.v13i1.4845

[17] R. Normasari, B. Purwanto, and D. Tinduh, “Protective effect of rutinoside on oxidative induced articular cartilage damage and catabolic activity in rat chondrocyte,” Pharmacognosy Journal, vol. 16, no. 2, pp. 360–365, 2024b, doi: https://doi.org/10.5530/pj.2024.16.55

[18] S. Kumar and A. K. Pandey, “Chemistry and biological activities of flavonoids: An overview,” The Scientific World Journal, 2013, p. 162750, doi: https://doi.org/10.1155/2013/162750

[19] S. R. Akash, A. Tabassum, L. M. Aditee, A. Rahman, M. I. Hossain, M. A. Hannan, and M. J. Uddin, “Pharmacological insight of rutin as a potential candidate against peptic ulcer,” Biomedicine and Pharmacotherapy, vol. 177, p. 116961, 2024, doi: https://doi.org/10.1016/j.biopha.2024.116961

[20] S. Rahmani et al., “The protective effects of rutin on the liver, kidneys, and heart by counteracting organ toxicity caused by synthetic and natural compounds,” Food Science & Nutrition, vol. 11, no. 1, pp. 39–56, 2023, doi: https://doi.org/10.1002/fsn3.3041

[21] S. Singh et al., “Rutin protects t-butyl hydroperoxide-induced oxidative impairment via modulating the Nrf2 and iNOS activity,” Phytomedicine, vol. 55, pp. 92–104, 2019, doi: https://doi.org/10.1016/j.phymed.2018.07.009

[22] S. Suganya and T. Sumathi, “Rutin a dietary flavonoid protects against altered neurobehavioral, membrane bound enzymes and striatal damage induced by 3-nitropropionic acid in male Wistar rats,” International Journal of Pharmacognosy and Phytochemical Research, vol. 8, no. 7, pp. 1191–1199, 2016, doi: https://doi.org/10.1016/j.crphar.2022.100130

[23] T. Kauss et al., “Rutoside decreases human macrophage-derived inflammatory mediators and improves clinical signs in adjuvant-induced arthritis,” Arthritis Research & Therapy, vol. 10, no. 1, R19, 2008, doi: https://doi.org/10.1186/ar2372

[24] T. Toprak et al., “Protective effect of chlorogenic acid on renal ischemia/reperfusion injury in rats,” Archivio Italiano Di Urologia e Andrologia, vol. 92, no. 2, pp. 153–157, 2020, doi: https://doi.org/10.4081/aiua.2020.2.153

[25] X. Chen et al., “Rutin inhibited the advanced glycation end products-stimulated inflammatory response and extra-cellular matrix degeneration via targeting TRAF-6 and BCL-2 proteins in mouse model of osteoarthritis,” Aging (Albany NY), vol. 13, no. 18, pp. 22134–22147, 2021, doi: https://doi.org/10.18632/aging.203470

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Published

2026-01-25

How to Cite

Normasari, R., & Pratiwi, Y. (2026). Acute Oral Toxicity Assessment of Rutinoside on Renal Histopathology in Wistar Rats. International Journal of Health and Information System, 3(3), 6. https://doi.org/10.47134/ijhis.v3i3.79

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