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

Carmen De Miguel, Randee Sedaka, Malgorzata Kasztan, Jeremie M. Lever, Michelle Sonnenberger, Andrew Abad, Chunhua Jin, Pamela K Carmines, David M. Pollock, Jennifer S. Pollock

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere13227
JournalActa Physiologica
Volume226
Issue number1
DOIs
StatePublished - May 2019

Fingerprint

Salts
Inflammation
Kidney
Wounds and Injuries
Diet
Cell Death
tauroursodeoxycholic acid
Low Density Lipoprotein Receptor-Related Protein-2
Transgenic Rats
Albuminuria
Microvilli
Bile Acids and Salts
Proteinuria
Permeability
Cell Count
Biomarkers
Blood Pressure
T-Lymphocytes
Liver

Keywords

  • CD4 T cells
  • ET receptors
  • cell death
  • high salt diet
  • renal injury

ASJC Scopus subject areas

  • Physiology

Cite this

De Miguel, C., Sedaka, R., Kasztan, M., Lever, J. M., Sonnenberger, M., Abad, A., ... Pollock, J. S. (2019). Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt-induced renal injury and inflammation. Acta Physiologica, 226(1), [e13227]. https://doi.org/10.1111/apha.13227

Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt-induced renal injury and inflammation. / De Miguel, Carmen; Sedaka, Randee; Kasztan, Malgorzata; Lever, Jeremie M.; Sonnenberger, Michelle; Abad, Andrew; Jin, Chunhua; Carmines, Pamela K; Pollock, David M.; Pollock, Jennifer S.

In: Acta Physiologica, Vol. 226, No. 1, e13227, 05.2019.

Research output: Contribution to journalArticle

De Miguel, C, Sedaka, R, Kasztan, M, Lever, JM, Sonnenberger, M, Abad, A, Jin, C, Carmines, PK, Pollock, DM & Pollock, JS 2019, 'Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt-induced renal injury and inflammation', Acta Physiologica, vol. 226, no. 1, e13227. https://doi.org/10.1111/apha.13227
De Miguel C, Sedaka R, Kasztan M, Lever JM, Sonnenberger M, Abad A et al. Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt-induced renal injury and inflammation. Acta Physiologica. 2019 May;226(1). e13227. https://doi.org/10.1111/apha.13227
De Miguel, Carmen ; Sedaka, Randee ; Kasztan, Malgorzata ; Lever, Jeremie M. ; Sonnenberger, Michelle ; Abad, Andrew ; Jin, Chunhua ; Carmines, Pamela K ; Pollock, David M. ; Pollock, Jennifer S. / Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt-induced renal injury and inflammation. In: Acta Physiologica. 2019 ; Vol. 226, No. 1.
@article{b087ec75ca4e46e89765687bf794f18a,
title = "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.",
keywords = "CD4 T cells, ET receptors, cell death, high salt diet, renal injury",
author = "{De Miguel}, Carmen and Randee Sedaka and Malgorzata Kasztan and Lever, {Jeremie M.} and Michelle Sonnenberger and Andrew Abad and Chunhua Jin and Carmines, {Pamela K} and Pollock, {David M.} and Pollock, {Jennifer S.}",
year = "2019",
month = "5",
doi = "10.1111/apha.13227",
language = "English (US)",
volume = "226",
journal = "Acta Physiologica",
issn = "1748-1708",
number = "1",

}

TY - JOUR

T1 - Tauroursodeoxycholic acid (TUDCA) abolishes chronic high salt-induced renal injury and inflammation

AU - De Miguel, Carmen

AU - Sedaka, Randee

AU - Kasztan, Malgorzata

AU - Lever, Jeremie M.

AU - Sonnenberger, Michelle

AU - Abad, Andrew

AU - Jin, Chunhua

AU - Carmines, Pamela K

AU - Pollock, David M.

AU - Pollock, Jennifer S.

PY - 2019/5

Y1 - 2019/5

N2 - 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.

AB - 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.

KW - CD4 T cells

KW - ET receptors

KW - cell death

KW - high salt diet

KW - renal injury

UR - http://www.scopus.com/inward/record.url?scp=85059011116&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059011116&partnerID=8YFLogxK

U2 - 10.1111/apha.13227

DO - 10.1111/apha.13227

M3 - Article

C2 - 30501003

AN - SCOPUS:85059011116

VL - 226

JO - Acta Physiologica

JF - Acta Physiologica

SN - 1748-1708

IS - 1

M1 - e13227

ER -