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
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引用次数: 0
Abstract
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.
期刊介绍：
Biological Trace Element Research provides a much-needed central forum for the emergent, interdisciplinary field of research on the biological, environmental, and biomedical roles of trace elements. Rather than confine itself to biochemistry, the journal emphasizes the integrative aspects of trace metal research in all appropriate fields, publishing human and animal nutritional studies devoted to the fundamental chemistry and biochemistry at issue as well as to the elucidation of the relevant aspects of preventive medicine, epidemiology, clinical chemistry, agriculture, endocrinology, animal science, pharmacology, microbiology, toxicology, virology, marine biology, sensory physiology, developmental biology, and related fields.
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