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Renoprotective role of Ebselen on developmental renal toxicity following gestational Methylmercury exposure in Wistar rats

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Author Affiliations

  • 1Department of Zoology, Maharani Janki Kunwar College, Bettiah, West Champaran-845438, Bihar, India
  • 2Department of Zoology, Mahatma Gandhi Central University, Motihari, East Champaran -845438, Bihar, India
  • 3Department of Zoology, Maharani Janki Kunwar College, Bettiah, West Champaran-845438, Bihar, India

Res. J. of Pharmaceutical Sci., Volume 14, Issue (1), Pages 4-14, June,30 (2025)

Abstract

Methylmercury (MeHg) crosses the placental and blood-brain barriers, posing risks to neonates and adults. While its neurotoxic effects during gestation are well-documented, its impact on kidney development is less understood. This study explored the renal toxicity of gestational MeHg exposure (0.5 mg/kg and 5 mg/kg via oral gavages) from Gestational Day 4 to Post-Natal Day 1. MeHg exposure resulted in reduced body and kidney weights and elevated nephrotoxicity markers in serum and urine, indicating renal dysfunction. Histopathological analysis showed a decrease in cortical area and glomeruli count, reflecting impaired renal development. Molecular studies revealed upregulation of MMP9, a tissue injury marker, with alterations in Nephrin, Villin, and GDNF expression, essential for renal function and growth. Hypomethylation of the MMP9 promoter, confirmed by ChIP-PCR, suggested epigenetic dysregulation as a mechanism of toxicity. Ebselen, an antioxidant, demonstrated renoprotective effects by restoring cortical area and glomeruli count, normalizing nephrotoxicity markers, and reducing MMP9 expression. Ebselen's effects were linked to increased MMP9 promoter methylation, countering MeHg-induced epigenetic changes. These findings highlight Ebselen’s potential to mitigate oxidative stress and epigenetic disruptions, making it a promising therapeutic agent to address developmental renal toxicity caused by gestational MeHg exposure.

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