Transl Clin Pharmacol.  2017 Sep;25(3):114-116. 10.12793/tcp.2017.25.3.114.

Inhibition of indoxyl sulfate-induced intrarenal renin-angiotensin system activation: targeting the aryl hydrocarbon receptor

• Akbar MF

• KMID: 2390929
• DOI: http://doi.org/10.12793/tcp.2017.25.3.114

Abstract

Indoxyl sulfate, a protein-bound uremic toxin, leads to CKD (chronic kidney disease) progression and its complications through the activation of AhR (aryl hydrocarbon receptor) and RAS (renin-angiotensin system). Inhibition of these pathways may slow the development of CKD and CKD-associated complications.

Keyword

Chronic Kidney Disease; Indoxyl Sulfate; Aryl Hydrocarbon Receptor; Renin-Angiotensin System

MeSH Terms

Indican
Kidney
Receptors, Aryl Hydrocarbon*
Renal Insufficiency, Chronic
Renin-Angiotensin System*
Indican
Receptors, Aryl Hydrocarbon

Figure

• 

  Figure 1 The mechanism by which IS (indoxyl sulfate) causes cell damage through the activation of the AhR (aryl hydrocarbon receptor) and RAS (renin-angiotensin system). In cultured cell and animal models of chronic kidney disease (CKD), Sun et al.[3] found that IS causes the activation of the RAS, which in turn leads to an inflammatory reaction, increasing levels of free radicals, and the synthesis of proteins causing fibrosis. Watanabe et al.4] using a human umbilical cord blood vessel model, showed that IS induces inflammation and cellular oxidative stress via AhR activation. The result of these studies together present the hypothesis that upon IS binding, the AhR induces inflammation, oxidative stress, and an increase in the synthesis of RAS proteins, which ultimately enhance fibrosis. Modified from Pernomian and da Silva.[12]

Reference

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