Biomedicines (Feb 2023)

Integration of Ultrastructural and Computational Approaches Reveals the Protective Effect of Astaxanthin against BPA-Induced Nephrotoxicity

  • Refaat A. Eid,
  • Muhammad Alaa Edeen,
  • Mohamed A. Soltan,
  • Mubarak Al-Shraim,
  • Mohamed Samir A. Zaki,
  • Saleh M. Al-Qahtani,
  • Eman Fayad,
  • Eman T. Salem,
  • Waleed K. Abdulsahib,
  • Hebatallah Emam,
  • Hesham M. Hassan

DOI
https://doi.org/10.3390/biomedicines11020421
Journal volume & issue
Vol. 11, no. 2
p. 421

Abstract

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Background: Bisphenol A (BPA) is an environmental contaminant that can induce deleterious organ effects. Human Cytochrome P450 CYP2C9 enzyme belongs to the essential xenobiotic-metabolizing enzymes, producing ROS as a byproduct. Astaxanthin (ATX) is a powerful antioxidant that protects organs and tissues from the damaging effects of oxidative stress caused by various diseases. Aim of the study: This study investigated the possible protective impacts of ATX against BPA-induced nephrotoxicity and its underlying mechanism. Materials and methods: Kidney tissues were isolated and examined microscopically from control, protected, and unprotected groups of rats to examine the potential protective effect of ATX against nephrotoxicity. Moreover, a molecular dynamic (MD) simulation was conducted to predict the performance of ATX upon binding to the active site of P450 CYP2C9 protein receptor as a potential mechanism of ATX protective effect. Results: Implemented computational methods revealed the possible underlying mechanism of ATX protection; the protective impact of ATX is mediated by inhibiting P450 CYP2C9 through binding to its dimeric state where the RMSF value for apo-protein and ATX-complex system were 5.720.57 and 1.040.41, respectively, implicating the ATX-complex system to have lesser variance in its residues, leading to the prevention of ROS excess production, maintaining the oxidant-antioxidant balance and re-establishing the proper mitochondrial functionality. Furthermore, the experimental methods validated in silico outcomes and revealed that ATX therapy effectively restored the typical histological architecture of pathological kidney tissues. Conclusions: ATX prevents BPA-induced nephrotoxicity by controlling oxidative imbalance and reversing mitochondrial dysfunction. These outcomes shed new light on the appropriate use of ATX as a treatment or prophylactic agent for these severe conditions.

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