Scholarlink

<p>This study investigated the molecular mechanisms underlying lead (Pb)-induced nephropathy and assessed the nephroprotective potential of Polydatin (PD). Forty male Wistar rats were divided into five groups (n = 8/group): negative control (NC), normal rats treated with 200 mg/kg/day of PD (NPD200), positive control (PC) receiving Pb only (30 mg/kg/day), and two groups co-administered Pb with PD (100 or 200 mg/kg/day). Serum and urine Pb levels were determined by an atomic absorption spectrophotometer. Markers of renal tissue damage (TGF-β/iNOS/NGLA/KIM-1) and renoprotective molecules (Nrf2/AMKα/AKT1) genes and proteins were measured by quantitative RT-PCR and Immunohistochemistry, respectively. ELISA was used to quantify markers of oxidative stress (GSH/Gpx1/CAT/MDA/H<sub>2</sub>O<sub>2</sub>) and inflammation (TNFα/IL1β/IL6/IL-10/IFN-γ). The PC group exhibited significant renal damage, including abnormal histology, increased apoptosis, elevated serum creatinine and urea, proteinuria, and polyuria. The PC renal tissues also showed substantial upregulations of iNOS/TGF-β/KIM-1/NGAL, whilst Nrf2/AMPK/AKT declined compared to healthy rats. Moreover, levels of oxidative stress (MDA/H<sub>2</sub>O<sub>2</sub>) and inflammatory (TNF-α/IL1β/IL6) markers were substantially higher in the PC renal specimens, whereas the antioxidants (GSH/GPx/CAT) with IL-10 and IFN-γ decreased than the NC group. Co-administration of PD with Pb improved renal biochemical parameters, attenuated histopathological changes and apoptosis, reduced the expression of iNOS/TGF-β/KIM-1, concentrations of oxidative stress and pro-inflammatory markers, whilst enhanced antioxidants and Nrf2/AMPK/AKT/IL-10/IFN-γ levels. However, the protective effects of the PD high-dose regimen were significantly greater than the low-dose protocol. In conclusion, PD prophylactic regimens mitigated Pb-induced nephrotoxicity by targeting oxidative stress and inflammation, with the high-dose protocol demonstrating superior nephroprotective efficacy.</p> Graphical Abstract <p>Schematic representation of the proposed protective effects of polydatin (PD) against lead (Pb)-induced nephrotoxicity in Wistar rats. Pb exposure leads to oxidative stress, inflammation, apoptosis, and renal injury, as evidenced by increased levels of H₂O₂, MDA, TNF-α, IL-1β, IL-6, iNOS, TGF-β, Caspase-3, NGAL, and KIM-1, alongside the downregulation of antioxidant molecules (GSH, CAT, GPx1), anti-inflammatory cytokines (IL-10, IFN-γ), and the renoprotective Nrf2/AMPKα/AKT1 pathway. PD administration mitigates Pb-induced nephrotoxicity by counteracting oxidative stress, reducing inflammatory cytokine expression, and restoring antioxidant defence mechanisms, thereby preserving renal structure and function. The red arrows indicate Pb-induced pathological changes, while the dotted inhibitory lines highlight the protective effects of PD.</p> <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Polydatin Mitigates Lead-Induced Nephropathy by Modulating Oxidative Stress, Inflammation, and the AMPK/AKT/Nrf2 Pathway in Rats

  • 期刊论文

  • 发表日期：

    2025年3月12日

查看全文
  • Naief Dahran,
  • Mohammad A. Alobaidy,
  • Wejdan H. Owaydhah,
  • Ehdaa K. A. Soubahi,
  • Alaa A. Eisa,
  • Nani Nasreldin,
  • Hossam Gadalla,
  • Bassem Refaat,
  • Mohamed E. El-Boshy

摘要

This study investigated the molecular mechanisms underlying lead (Pb)-induced nephropathy and assessed the nephroprotective potential of Polydatin (PD). Forty male Wistar rats were divided into five groups (n = 8/group): negative control (NC), normal rats treated with 200 mg/kg/day of PD (NPD200), positive control (PC) receiving Pb only (30 mg/kg/day), and two groups co-administered Pb with PD (100 or 200 mg/kg/day). Serum and urine Pb levels were determined by an atomic absorption spectrophotometer. Markers of renal tissue damage (TGF-β/iNOS/NGLA/KIM-1) and renoprotective molecules (Nrf2/AMKα/AKT1) genes and proteins were measured by quantitative RT-PCR and Immunohistochemistry, respectively. ELISA was used to quantify markers of oxidative stress (GSH/Gpx1/CAT/MDA/H2O2) and inflammation (TNFα/IL1β/IL6/IL-10/IFN-γ). The PC group exhibited significant renal damage, including abnormal histology, increased apoptosis, elevated serum creatinine and urea, proteinuria, and polyuria. The PC renal tissues also showed substantial upregulations of iNOS/TGF-β/KIM-1/NGAL, whilst Nrf2/AMPK/AKT declined compared to healthy rats. Moreover, levels of oxidative stress (MDA/H2O2) and inflammatory (TNF-α/IL1β/IL6) markers were substantially higher in the PC renal specimens, whereas the antioxidants (GSH/GPx/CAT) with IL-10 and IFN-γ decreased than the NC group. Co-administration of PD with Pb improved renal biochemical parameters, attenuated histopathological changes and apoptosis, reduced the expression of iNOS/TGF-β/KIM-1, concentrations of oxidative stress and pro-inflammatory markers, whilst enhanced antioxidants and Nrf2/AMPK/AKT/IL-10/IFN-γ levels. However, the protective effects of the PD high-dose regimen were significantly greater than the low-dose protocol. In conclusion, PD prophylactic regimens mitigated Pb-induced nephrotoxicity by targeting oxidative stress and inflammation, with the high-dose protocol demonstrating superior nephroprotective efficacy.

Graphical Abstract

Schematic representation of the proposed protective effects of polydatin (PD) against lead (Pb)-induced nephrotoxicity in Wistar rats. Pb exposure leads to oxidative stress, inflammation, apoptosis, and renal injury, as evidenced by increased levels of H₂O₂, MDA, TNF-α, IL-1β, IL-6, iNOS, TGF-β, Caspase-3, NGAL, and KIM-1, alongside the downregulation of antioxidant molecules (GSH, CAT, GPx1), anti-inflammatory cytokines (IL-10, IFN-γ), and the renoprotective Nrf2/AMPKα/AKT1 pathway. PD administration mitigates Pb-induced nephrotoxicity by counteracting oxidative stress, reducing inflammatory cytokine expression, and restoring antioxidant defence mechanisms, thereby preserving renal structure and function. The red arrows indicate Pb-induced pathological changes, while the dotted inhibitory lines highlight the protective effects of PD.