Abstract
Uremic encephalopathy is a severe complication of renal failure. The underlying pathogenesis is unknown although several mechanisms have been suggested. Renal failure causes oxidative stress leading to cardiovascular complications. It has been suggested as the potential mediator of uremic encephalopathy as well, but it is largely unknown whether brain tissue itself undergoes oxidative damage in uremia. The aim of our experiment was to analyze oxidative stress markers in different brain regions in an animal model of acute kidney injury (AKI). AKI was induced by ischemia-reperfusion injury in male Wistar rats. Urine was collected in metabolic cages after 24 h. Samples of plasma and several brain regions were collected after 48 h. Markers of lipid peroxidation, protein oxidation and total antioxidant capacity were assessed. Renal failure was confirmed by high plasma creatinine, urea and urinary albumin to creatinine ratio. Our data confirmed increased systemic oxidative stress in the AKI group with plasma concentrations of markers of oxidative damage being twice as high compared to the sham-operated control group. No effect was seen in the urine. In the hippocampus, lipid and protein oxidation was higher, while antioxidant capacity was lower in the rats with AKI. Lipid oxidation markers in the frontal cortex were higher by 33%. No differences to controls were found in the cerebellum and hypothalamus. In conclusion, our results indicate that AKI leads to oxidative stress in the brain, especially in the hippocampus and in the frontal cortex. This kidney-brain crosstalk mediated by increased oxidative stress might explain some of the symptoms of uremic encephalopathy. The causes and consequences of oxidative damage observed in the brain during AKI remain to be elucidated.
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This study was supported by the Ministry of Education of the Slovak Republic – grant number VEGA 1/0223/15 and by the Research and Development Operational Program funded by the ERDF – project ITMS 26240120027.
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Kovalčíková, A., Gyurászová, M., Vavrincová-Yaghi, D. et al. Oxidative stress in the brain caused by acute kidney injury. Metab Brain Dis 33, 961–967 (2018). https://doi.org/10.1007/s11011-018-0204-8
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DOI: https://doi.org/10.1007/s11011-018-0204-8