Evaluation of brain and kidney energy metabolism in an animal model of contrast-induced nephropathy

Abstract

Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients, occurring from 24 to 48 h and up to 5 days after the administration of iodinated contrast media. Encephalopathy may accompany acute renal failure and presents with a complex of symptoms progressing from mild sensorial clouding to delirium and coma. The mechanisms responsible for neurological complications in patients with acute renal failure are still poorly known, but several studies suggest that mitochondrial dysfunction plays a crucial role in the pathogenesis of uremic encephalopathy. Thus, we measured mitochondrial respiratory chain complexes and creatine kinase activities in rat brain and kidney after administration of contrast media. Wistar rats were submitted to 6.0 ml/kg meglumine/sodium diatrizoate administration via the tail vein (acute renal failure induced by contrast media) and saline in an equal volume with the radiocontrast material (control group); 6 days after, the animals were killed and kidney and brain were obtained. The results showed that contrast media administration decreased complexes I and IV activities in cerebral cortex; in prefrontal cortex, complex I activity was inhibited. On the other hand, contrast media administration increased complexes I and II-III activities in hippocampus and striatum and complex IV activity in hippocampus. Moreover, that administration of contrast media also decreased creatine kinase activity in the cerebral cortex. The present findings suggest that the inhibition of mitochondrial respiratory chain complexes and creatine kinase caused by the acute renal failure induced by contrast media administration may be involved in the neurological complications reported in patients and might play a role in the pathogenesis of the encephalopathy caused by acute renal failure.

Acute renal failure potentiates brain energy dysfunction elicited by methylmalonic acid

“…It was then observed that acute renal failure induced by gentamicin administration provoked a significant decrease in creatine kinase activity in brain and particularly in kidney of rats. Similar findings have already been showed in other animal models of acute kidney injury (Roza et al, 2011). On the other hand, it was previously reported that the nephrotoxicity in other animal models of acute renal failure induced by cisplatin and aristolochic acid involves mitochondrial injury, including decrease of cytochrome c oxidase activity, as well as mtDNA depletion and respiratory chain complexes I and II (Zsengellér et al, 2012; Jiang et al, 2013).…”

In vivo nephroprotective efficacy of propolis against contrast-induced nephropathy

“…In addition to cytotoxic effects mediated by oxygen free radicals, renal toxicity can also be caused by direct effects on tubular cells (16). These events coupled with medullary ischemia from renal vasoconstriction, collectively contribute to CIN (17).…”

Contrast Induced Acute Kidney Injury and Direct Cytotoxicity of Iodinated Radiocontrast Media on Renal Proximal Tubule Cells

“…Lei et al (2018) determined that exposure to iohexol or iodixanol induced a significant increase in mitochondrial ROS and mitochondrial membrane potential in HK-2 cells. An in vivo investigation on the effects of RCM on the electron transport chain determined that exposure of male Wistar albino rats to 1.95 g×I/ml of diatrizaote tended to decrease renal complex I and III activity, although not to a significant degree (Roza et al, 2011). As one would expect, significant mitochondrial dysfunction results in insufficient ATP for a cell to maintain its cellular functions, resulting in activation of the intrinsic apoptotic pathways; however, the source of mitochondrial dysfunction in response to RCM exposure has yet to be identified (Haller and Hizoh, 2004).…”