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<p>Quercetin is widely used in dietary supplements, yet its sub-acute organ safety profile in healthy organisms remains incompletely characterized. This study evaluated dose-dependent effects of intraperitoneal quercetin administration in healthy female Wistar rats (<i>n</i> = 6/group) receiving normal saline (control) or quercetin (5, 10, 20, or 30&#xa0;mg/kg) every 72&#xa0;h for 21 days. Endpoints included body and organ weights, serum biochemistry, hematology, systemic and tissue oxidative stress markers, and semi-quantitative multi-organ histopathology. Quercetin at ≥ 20&#xa0;mg/kg significantly reduced percent weight gain (Dunn’s test vs. control: <i>p</i> = 0.041 and <i>p</i> = 0.008, respectively) and increased liver, kidney, and spleen relative weight, with concurrent leukocytosis and lymphocytosis. Despite these changes, all serum hepatic, renal, and systemic oxidative stress markers were preserved across groups (Kruskal–Wallis, all <i>p</i> &gt; 0.05). In contrast, liver and kidney tissue at ≥ 20&#xa0;mg/kg showed elevated glutathione, superoxide dismutase, and catalase alongside reduced malondialdehyde. Histopathology revealed dose-related structural alterations in kidney, liver, and spleen at doses ≥ 20&#xa0;mg/kg; cardiac changes were mild-to-moderate only at 30&#xa0;mg/kg. Serum biomarkers consistently indicated preserved organ function despite concurrent tissue-level injury, demonstrating that conventional markers underestimate early structural damage. The co-occurrence of tissue antioxidant upregulation with histological lesions reflects a compensatory stress response consistent with hormesis. These findings underscore the value of integrating histopathological endpoints into preclinical safety evaluation of quercetin.</p>

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Sub-acute intraperitoneal quercetin administration causes dose-dependent organ histopathology and oxidative stress in healthy rats: dissociation between serum biomarkers and tissue-level structural injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月11日

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  • Nasreen S. Hamad,
  • Dlzar D. Ghafoor,
  • Hezha O. Rasul

摘要

Quercetin is widely used in dietary supplements, yet its sub-acute organ safety profile in healthy organisms remains incompletely characterized. This study evaluated dose-dependent effects of intraperitoneal quercetin administration in healthy female Wistar rats (n = 6/group) receiving normal saline (control) or quercetin (5, 10, 20, or 30 mg/kg) every 72 h for 21 days. Endpoints included body and organ weights, serum biochemistry, hematology, systemic and tissue oxidative stress markers, and semi-quantitative multi-organ histopathology. Quercetin at ≥ 20 mg/kg significantly reduced percent weight gain (Dunn’s test vs. control: p = 0.041 and p = 0.008, respectively) and increased liver, kidney, and spleen relative weight, with concurrent leukocytosis and lymphocytosis. Despite these changes, all serum hepatic, renal, and systemic oxidative stress markers were preserved across groups (Kruskal–Wallis, all p > 0.05). In contrast, liver and kidney tissue at ≥ 20 mg/kg showed elevated glutathione, superoxide dismutase, and catalase alongside reduced malondialdehyde. Histopathology revealed dose-related structural alterations in kidney, liver, and spleen at doses ≥ 20 mg/kg; cardiac changes were mild-to-moderate only at 30 mg/kg. Serum biomarkers consistently indicated preserved organ function despite concurrent tissue-level injury, demonstrating that conventional markers underestimate early structural damage. The co-occurrence of tissue antioxidant upregulation with histological lesions reflects a compensatory stress response consistent with hormesis. These findings underscore the value of integrating histopathological endpoints into preclinical safety evaluation of quercetin.