Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification

Area of Science:

• Nephrology
• Cardiovascular Science
• Neuroscience

Background:

• Vascular calcification is a common complication of end-stage renal disease (ESRD), contributing to cardiovascular and cerebrovascular events.
• Sodium thiosulfate (STS) exhibits antioxidant and calcium-chelating properties, with prior studies suggesting its potential in preventing vascular calcification.
• The impact of STS on cerebral function and mitochondrial dysfunction in the context of ESRD-induced vascular calcification remains underexplored.

Purpose of the Study:

• To investigate the neuroprotective effects of Sodium thiosulfate (STS) in a rat model of end-stage renal disease (ESRD)-induced vascular calcification.
• To evaluate the impact of STS on brain oxidative stress and mitochondrial function.
• To compare the efficacy of STS as a preventive versus a curative agent.

Main Methods:

• A rat model was established using adenine administration to induce vascular calcification and renal failure.
• Sodium thiosulfate (STS) was administered either preventively or curatively.
• Assessment included blood and urine chemistries, aortic histopathology, brain oxidative stress markers (TBARS, CAT, SOD, GPx), and mitochondrial function assays (respiratory enzymes, P/O ratio, RCR).

Main Results:

• STS demonstrated renal protective effects, confirmed by blood/urine chemistries and aortic histopathology, in both preventive and curative administration modes.
• STS administration significantly reduced brain oxidative stress and preserved mitochondrial function, including respiratory enzyme activities and physiological parameters.
• Curative STS treatment yielded more prominent neuroprotection, evidenced by near-normal brain oxidative stress markers and preserved mitochondrial function, compared to preventive treatment.

Conclusions:

• Sodium thiosulfate (STS) exerts significant protective effects on the brain, particularly on mitochondria, in the context of ESRD-induced vascular calcification.
• The curative administration of STS proved more effective in preserving brain mitochondrial integrity and function than concomitant preventive treatment.
• Findings highlight STS as a potential therapeutic agent for mitigating cerebrovascular complications associated with ESRD.