Proteomic characterization of acyclovir-induced nephrotoxicity in a mouse model

Area of Science:

• Nephrology
• Proteomics
• Toxicology

Background:

• Acyclovir (ACV) is a crucial antiviral medication.
• ACV use is restricted by significant nephrotoxicity.
• Understanding ACV-induced kidney damage mechanisms is vital.

Purpose of the Study:

• To investigate the molecular mechanisms of ACV-induced nephrotoxicity.
• To identify key proteins altered during ACV-induced kidney injury.
• To explore the roles of VEGF and FGF in ACV nephrotoxicity recovery.

Main Methods:

• Proteomic analysis using mass spectrometry and 2D-PAGE on mouse kidney samples.
• Administration of ACV to ICR mice at varying doses (150 or 600 mg/kg/day) for 9 days.
• Biochemical assays for serum creatinine and urea nitrogen, and histopathological examination of kidneys.
• Western blotting to confirm differential protein expression.

Main Results:

• ACV administration significantly elevated serum creatinine and urea nitrogen levels.
• Histopathology revealed kidney damage and reduced VEGF/VEGFR2 expression.
• Proteomic analysis identified 20 differentially expressed proteins, including six key proteins associated with ACV nephrotoxicity.
• Upregulated proteins like α-crystallin and peroxiredoxin 1 suggest oxidative stress and mitochondrial injury.

Conclusions:

• ACV-induced nephrotoxicity involves oxidative damage and mitochondrial injury.
• Proteomic insights highlight specific proteins involved in ACV kidney damage.
• VEGF and FGF signaling pathways may be critical for renal tissue repair post-ACV exposure.