Pharmacological inhibition of Vanin-1 is not protective in models of acute and chronic kidney disease.

Pharmacological inhibition of Vanin-1 is not protective in models of acute and chronic kidney disease. Am J Physiol Renal Physiol. 2020 Nov 16;: Authors: Unterschemmann K, Ehrmann A, Herzig I, Andreevski AL, Lustig K, Schmeck C, Eitner F, Grundmann M Abstract Oxidative stress is a key concept in basic, translational and clinical research to understand the pathophysiology of various disorders, including cardiovascular and renal diseases. While attempts to directly reduce oxidative stress with redox-active substances have until now largely failed to prove clinical benefit, indirect approaches to combat oxidative stress enzymatically gain further attention as potential therapeutic strategies. The pantetheinase Vanin-1 is expressed on kidney proximal tubular cells and its reaction product cysteamine is described to negatively affect redox homeostasis by inhibiting the replenishment of cellular anti-oxidative glutathione stores. Vanin-1 deficient mice were shown to be protected against various oxidative stress damages. The aim of this study was to elucidate whether pharmacological inhibition of Vanin-1 protects mice from oxidative stress related acute or chronic kidney injury as well. By studying renal ischemia reperfusion injury and Col4α3-/- (Alport syndrome) mice and in vitro hypoxia/reoxygenation on human proximal tubular cells we found that treatment with a selective and potent Vanin‑1 inhibitor resulted in ample inhibition of enz...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research