Oxidative stress in the brain caused by acute kidney injury

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.

Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study

“…A high concentration of redox signaling of ROS is commonly observed with cell damage and metabolic dysregulation, including lipid peroxidation, and irretrievable protein and DNA degeneration [ 16 ]. Moreover, the trigger of oxidative stress in a coordinated manner can disseminate the impairment to extrahepatic organs, including the failure of kidney, brain, and lung, which seem to indiscriminately oxidize almost all molecules in tissues [ 17 , 18 , 19 ]. However, under normal oxygen metabolism, ROS is perceived to be a molecular secondary messenger involved in the signal transduction mechanism in response to cytokines, hormones, and adenosine triphosphate (ATP), regulating the biological and physiological processes [ 20 ].…”

The influence of renal ischemia-reperfusion injury on remote organs

“…Brain insult in the different levels of structure, biochemistry, inflammation, and behavior reported renal ischemia consequence. [ 6 7 8 9 10 11 ] Inflammatory and functional changes of male mice’s brain following ischemic AKI have been shown by Liu et al . [ 10 ] Most of these researches have been done on male rats, but it is certain that kidney diseases are gender related.…”

Long non‐coding RNA Miat mediates cross-talk between the kidneys and hippocampus in the rat model of acute kidney injury

“…Hippocampus is a vulnerable brain region involved in uremic encephalopathy which is associated with deficits in a variety of cognitive and memory tasks in acute and chronic kidney diseases (Bugnicourt et al, 2013;Kovalčíková et al, 2018). As discussed earlier, the association between kidney and brain hippocampus has been identified by inflammation and cellular abnormalities in the hippocampus following AKI (Liu et al, 2008).…”