Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt‐induced renal injury and inflammation

Abstract

Aim: Chronic high salt intake exaggerates renal injury and inflammation, especially with the loss of functional ET B receptors. Tauroursodeoxycholic acid (TUDCA) is a chemical chaperone and bile salt that is approved for the treatment of hepatic diseases. Our aim was to determine whether TUDCA is reno-protective in a model of ET B receptor deficiency with chronic high salt-induced renal injury and inflammation. Methods: ET B -deficient and transgenic control rats were placed on normal (0.8% NaCl) or high salt (8% NaCl) diet for 3 weeks, receiving TUDCA (400 mg/kg/d; ip) or vehicle. Histological and biochemical markers of kidney injury, renal cell death and renal inflammation were assessed. Results: In ET B -deficient rats, high salt diet significantly increased glomerular and proximal tubular histological injury, proteinuria, albuminuria, excretion of tubular injury markers KIM-1 and NGAL, renal cortical cell death and renal CD4 + T cell numbers. TUDCA treatment increased proximal tubule megalin expression as well as prevented high salt diet-induced glomerular and tubular damage in ET B -deficient rats, as indicated by reduced kidney injury markers, decreased glomerular permeability and proximal tubule brush border restoration, as well as reduced renal inflammation. However, TUDCA had no significant effect on blood pressure. Conclusions: TUDCA protects against the development of glomerular and proximal tubular damage, decreases renal cell death and inflammation in the renal cortex in rats with ET B receptor dysfunction on a chronic high salt diet. These results highlight the potential use of TUDCA as a preventive tool against chronic high salt induced renal damage. K E Y W O R D SCD4 + T cells, cell death, ET B receptors, high salt diet, renal injury

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

“…Although a great deal of research focusing on the ER stress-dependent modulatory effect of TUDCA on inflammatory responses exists, several studies investigating the anti-inflammatory potential of this bile acid regardless of its ER stress-modifying activity have also been performed [162,163,170,171]. However, only one report clearly presented that TUDCA abolished salt-induced renal injury and inflammation in endothelin B receptor (ETB)-deficient rats independently on ER stress response, implying different mechanisms of its anti-inflammatory effects [171]. Indeed, TUDCA treatment did not decrease measures of ER stress as presented by the unchanged expressions of GRP78, ATF-4, ATF-6, sXBP-1, CHOP, and caspase-12, however, it markedly reduced salt-induced TNF-α excretion and CD4+ T lymphocyte accumulation in the renal cortex [171].…”

“…However, only one report clearly presented that TUDCA abolished salt-induced renal injury and inflammation in endothelin B receptor (ETB)-deficient rats independently on ER stress response, implying different mechanisms of its anti-inflammatory effects [171]. Indeed, TUDCA treatment did not decrease measures of ER stress as presented by the unchanged expressions of GRP78, ATF-4, ATF-6, sXBP-1, CHOP, and caspase-12, however, it markedly reduced salt-induced TNF-α excretion and CD4+ T lymphocyte accumulation in the renal cortex [171]. Interestingly, although other studies also clearly presented anti-inflammatory properties of TUDCA, its influence on the modulation of ER stress has not been evaluated [162,163,170].…”

Kidney research

“…Kidney research has been one major focus of publications of recent articles published in Acta physiologica . A number of articles deal with the elucidation of kidney disease models 1‐12 and the role of oxygen regulation in the kidney 13‐16 . This contribution focusses on articles that deal with kidney disease models and in the second part on articles that are related to the topic hypoxia and oxygen regulation.…”

Inflammation—Dysregulated inflammatory response and strategies for treatment

“…TNFα is an inducer of cell death and plays an important role in the development of salt‐sensitive kidney disease. There is an evidence that TUDCA may be a valuable therapeutic tool for chronic cardiovascular and renal diseases, which are exacerbated by high salt diets …”