Glibenclamide-mediated oxidative stress in zebrafish (Danio rerio) embryogenesis: A comprehensive analysis
Abstract
Given the escalating use of glibenclamide as a commonly prescribed antidiabetic medication, concerns have arisen regarding its potential ecological impact on aquatic organisms. This study presents a comprehensive analysis of the impact of glibenclamide exposure on the embryogenesis of zebrafish (Danio rerio), providing insights into the intricate dynamics of oxidative stress. Leveraging the transparency of zebrafish embryos and their genetic resemblance to humans, the study conducted real-time observations of developmental processes, employing rigorous toxicity assessments to elucidate concentration-dependent patterns in embryo mortality and malformations. The results revealed a substantial increase in embryo mortality rates with elevated glibenclamide concentrations, reaching 76% at the highest tested concentration of 750 µg L-1, underscoring its detrimental impact. Correspondingly, malformation rates surged at higher glibenclamide concentrations, with 69.4% of embryos exhibiting malformations at 750 µg L-1. Probit analysis determined a median lethal concentration of 329.3 µg L-1 and a median effective concentration of malformations of 401.9 µg L-1, categorizing glibenclamide as an embryolethal substance. Moreover, oxidative stress emerged as a pivotal mechanism, supported by increased lipid peroxidation, and altered antioxidant enzyme activity. The study delved into gene expression, revealing upregulated antioxidant-related genes and delayed expression of apoptosis-related genes. This research significantly enhances our understanding of the broader environmental implications of glibenclamide usage, emphasizing the interconnectedness of human health and the natural world. By highlighting the potential risks associated with glibenclamide exposure during embryonic development, it offers valuable insights into the ecological footprint of other pharmaceutical agents operating through similar mechanisms.
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