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<p>Chlorpyrifos, an organophosphorus pesticide commonly used in agriculture, has been associated with nephrotoxicity and other harmful effects. This study investigates the renoprotective effects of diosmin, a flavonoid known for its antioxidant and anti-inflammatory properties, against chlorpyrifos-induced kidney damage in rats. Male Wistar albino rats were exposed to chlorpyrifos at a dose of 10&#xa0;mg/kg for 28&#xa0;days, and the protective role of diosmin at a dose of 50&#xa0;mg/kg, orally, was assessed through various biochemical, histopathological, molecular, and computational analyses. Chlorpyrifos exposure significantly induced kidney damage by elevation of kidney functions and NGAL, as well as histopathological alteration. In addition, chlorpyrifos exposure induced renal inflammation as evidenced by upregulation of TLR4, HMGB1, p-NF-κB, TNF-α, IL-1β, and MPO levels. Besides, chlorpyrifos induced oxidative stress as evidenced by decreasing PPAR-γ, SIRT1, GSH, and SOD expressions associated with increased MDA levels. Furthermore, chlorpyrifos induced renal cell apoptosis, as proved by Bax and Bcl2 dysregulation. Interestingly, co-administration of diosmin with chlorpyrifos ameliorated these effects, restoring kidney function biomarkers, preserving histological structure, suppressing inflammatory burden, reducing oxidative stress parameters, and inhibiting apoptosis. In addition, the results of molecular docking confirmed the in vivo results. Taken together, diosmin exerts a renoprotective effect by attenuating chlorpyrifos-induced oxidative stress and inflammation, highlighting its potential as a therapeutic agent for mitigating pesticide-induced kidney injury.</p>

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Renoprotective effect of diosmin against chlorpyrifos-induced kidney injury is mediated by the regulation of TLR4/HMGB1/NF-κB, PPAR-γ/SIRT1, and Bax/Bcl2 signals

  • 期刊论文

  • 发表日期：

    2025年12月9日

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  • Duaa Althumairy,
  • Mohammad Bani Ismail,
  • Hamad Abu Zahra,
  • Badrah S. Alghamdi,
  • Hanan S. Althagafy,
  • Zainab Mohammed Mahmoud Omar,
  • Emad H. M. Hassanein,
  • Fares E. M. Ali

摘要

Chlorpyrifos, an organophosphorus pesticide commonly used in agriculture, has been associated with nephrotoxicity and other harmful effects. This study investigates the renoprotective effects of diosmin, a flavonoid known for its antioxidant and anti-inflammatory properties, against chlorpyrifos-induced kidney damage in rats. Male Wistar albino rats were exposed to chlorpyrifos at a dose of 10 mg/kg for 28 days, and the protective role of diosmin at a dose of 50 mg/kg, orally, was assessed through various biochemical, histopathological, molecular, and computational analyses. Chlorpyrifos exposure significantly induced kidney damage by elevation of kidney functions and NGAL, as well as histopathological alteration. In addition, chlorpyrifos exposure induced renal inflammation as evidenced by upregulation of TLR4, HMGB1, p-NF-κB, TNF-α, IL-1β, and MPO levels. Besides, chlorpyrifos induced oxidative stress as evidenced by decreasing PPAR-γ, SIRT1, GSH, and SOD expressions associated with increased MDA levels. Furthermore, chlorpyrifos induced renal cell apoptosis, as proved by Bax and Bcl2 dysregulation. Interestingly, co-administration of diosmin with chlorpyrifos ameliorated these effects, restoring kidney function biomarkers, preserving histological structure, suppressing inflammatory burden, reducing oxidative stress parameters, and inhibiting apoptosis. In addition, the results of molecular docking confirmed the in vivo results. Taken together, diosmin exerts a renoprotective effect by attenuating chlorpyrifos-induced oxidative stress and inflammation, highlighting its potential as a therapeutic agent for mitigating pesticide-induced kidney injury.