Agonists of peroxisome-proliferator activated receptor-gamma reduce renal ischemia/reperfusion injury.

A. Sivarajah, P. K. Chatterjee, N. Patel, Z. Todorovic, Y. Hattori, Paul Anthony James Brown, Keith Nicol Stewart, H. Mota-Filipe, C. Thiemermann

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Background/Aims: Recent evidence indicates that peroxisome-proliferator activated receptor (PPAR) agonists protect against ischemia/reperfusion (I/R) injury. Here we investigate the effects of the PPAR-gamma agonists, rosiglitazone and ciglitazone, on the renal dysfunction and injury caused by I/R of the rat kidney in vivo. Methods: Rosiglitazone or ciglitazone were administered to male Wistar rats prior to and during reperfusion. Biochemical indicators of renal dysfunction and injury were measured and histological scoring of kidney sections was used to assess renal injury. Expression of PPAR isoforms and intercellular adhesion molecule-1 during renal I/R were assessed using RT-PCR and Northern blot, respectively. Myeloperoxidase activity and activation of poly(ADPribose) polymerase (PARP) were used as indicators of polymorphonuclear (PMN) cell infiltration and oxidative stress, respectively. Results: Expression of PPAR-alpha, PPAR-beta and PPAR-gamma1 (but not PPAR-gamma2) was observed in kidneys with down-regulation of PPAR-a expression during renal I/R. Rosiglitazone and ciglitazone significantly reduced biochemical and histological signs of renal dysfunction and injury. Renal expression of ICAM-1 caused by I/R was reduced by rosiglitazone and ciglitazone which was reflected by decreased PMN infiltration into reperfused renal tissues. Both rosiglitazone and ciglitazone reduced PARP activation indicating a reduction of oxidative stress. Conclusion: These results suggest that the PPAR-gamma agonists rosiglitazone and ciglitazone reduce the renal dysfunction and injury associated with I/R of the kidney. We propose that one mechanism underlying the protective effects involves inhibition of the expression of ICAM-1, a reduction of PMN infiltration into renal tissues and subsequent reduction of oxidative stress. Copyright (C) 2003 S. Karger AG, Basel.

Original languageEnglish
Pages (from-to)267-276
Number of pages9
JournalAmerican Journal of Nephrology
Volume23
Issue number4
DOIs
Publication statusPublished - 2003

Keywords

  • kidney
  • reperfusion-injury
  • renal dysfunction
  • peroxisome-proliferator activated receptor rosiglitazone
  • ciglitazone
  • intercellular adhesion molecule-1
  • ISCHEMIA-REPERFUSION INJURY
  • CELL-ADHESION MOLECULES
  • PPAR-GAMMA
  • IN-VIVO
  • FAILURE
  • ROSIGLITAZONE
  • RATS
  • PROTECTS
  • LIGAND
  • PATHOPHYSIOLOGY

Cite this

Sivarajah, A., Chatterjee, P. K., Patel, N., Todorovic, Z., Hattori, Y., Brown, P. A. J., ... Thiemermann, C. (2003). Agonists of peroxisome-proliferator activated receptor-gamma reduce renal ischemia/reperfusion injury. American Journal of Nephrology, 23(4), 267-276. https://doi.org/10.1159/000072088

Agonists of peroxisome-proliferator activated receptor-gamma reduce renal ischemia/reperfusion injury. / Sivarajah, A.; Chatterjee, P. K.; Patel, N.; Todorovic, Z.; Hattori, Y.; Brown, Paul Anthony James; Stewart, Keith Nicol; Mota-Filipe, H.; Thiemermann, C.

In: American Journal of Nephrology, Vol. 23, No. 4, 2003, p. 267-276.

Research output: Contribution to journalArticle

Sivarajah, A, Chatterjee, PK, Patel, N, Todorovic, Z, Hattori, Y, Brown, PAJ, Stewart, KN, Mota-Filipe, H & Thiemermann, C 2003, 'Agonists of peroxisome-proliferator activated receptor-gamma reduce renal ischemia/reperfusion injury.', American Journal of Nephrology, vol. 23, no. 4, pp. 267-276. https://doi.org/10.1159/000072088
Sivarajah, A. ; Chatterjee, P. K. ; Patel, N. ; Todorovic, Z. ; Hattori, Y. ; Brown, Paul Anthony James ; Stewart, Keith Nicol ; Mota-Filipe, H. ; Thiemermann, C. / Agonists of peroxisome-proliferator activated receptor-gamma reduce renal ischemia/reperfusion injury. In: American Journal of Nephrology. 2003 ; Vol. 23, No. 4. pp. 267-276.
@article{9c800edc983949988b01cf5737bb895f,
title = "Agonists of peroxisome-proliferator activated receptor-gamma reduce renal ischemia/reperfusion injury.",
abstract = "Background/Aims: Recent evidence indicates that peroxisome-proliferator activated receptor (PPAR) agonists protect against ischemia/reperfusion (I/R) injury. Here we investigate the effects of the PPAR-gamma agonists, rosiglitazone and ciglitazone, on the renal dysfunction and injury caused by I/R of the rat kidney in vivo. Methods: Rosiglitazone or ciglitazone were administered to male Wistar rats prior to and during reperfusion. Biochemical indicators of renal dysfunction and injury were measured and histological scoring of kidney sections was used to assess renal injury. Expression of PPAR isoforms and intercellular adhesion molecule-1 during renal I/R were assessed using RT-PCR and Northern blot, respectively. Myeloperoxidase activity and activation of poly(ADPribose) polymerase (PARP) were used as indicators of polymorphonuclear (PMN) cell infiltration and oxidative stress, respectively. Results: Expression of PPAR-alpha, PPAR-beta and PPAR-gamma1 (but not PPAR-gamma2) was observed in kidneys with down-regulation of PPAR-a expression during renal I/R. Rosiglitazone and ciglitazone significantly reduced biochemical and histological signs of renal dysfunction and injury. Renal expression of ICAM-1 caused by I/R was reduced by rosiglitazone and ciglitazone which was reflected by decreased PMN infiltration into reperfused renal tissues. Both rosiglitazone and ciglitazone reduced PARP activation indicating a reduction of oxidative stress. Conclusion: These results suggest that the PPAR-gamma agonists rosiglitazone and ciglitazone reduce the renal dysfunction and injury associated with I/R of the kidney. We propose that one mechanism underlying the protective effects involves inhibition of the expression of ICAM-1, a reduction of PMN infiltration into renal tissues and subsequent reduction of oxidative stress. Copyright (C) 2003 S. Karger AG, Basel.",
keywords = "kidney, reperfusion-injury, renal dysfunction, peroxisome-proliferator activated receptor rosiglitazone, ciglitazone, intercellular adhesion molecule-1, ISCHEMIA-REPERFUSION INJURY, CELL-ADHESION MOLECULES, PPAR-GAMMA, IN-VIVO, FAILURE, ROSIGLITAZONE, RATS, PROTECTS, LIGAND, PATHOPHYSIOLOGY",
author = "A. Sivarajah and Chatterjee, {P. K.} and N. Patel and Z. Todorovic and Y. Hattori and Brown, {Paul Anthony James} and Stewart, {Keith Nicol} and H. Mota-Filipe and C. Thiemermann",
year = "2003",
doi = "10.1159/000072088",
language = "English",
volume = "23",
pages = "267--276",
journal = "American Journal of Nephrology",
issn = "0250-8095",
publisher = "S. Karger AG",
number = "4",

}

TY - JOUR

T1 - Agonists of peroxisome-proliferator activated receptor-gamma reduce renal ischemia/reperfusion injury.

AU - Sivarajah, A.

AU - Chatterjee, P. K.

AU - Patel, N.

AU - Todorovic, Z.

AU - Hattori, Y.

AU - Brown, Paul Anthony James

AU - Stewart, Keith Nicol

AU - Mota-Filipe, H.

AU - Thiemermann, C.

PY - 2003

Y1 - 2003

N2 - Background/Aims: Recent evidence indicates that peroxisome-proliferator activated receptor (PPAR) agonists protect against ischemia/reperfusion (I/R) injury. Here we investigate the effects of the PPAR-gamma agonists, rosiglitazone and ciglitazone, on the renal dysfunction and injury caused by I/R of the rat kidney in vivo. Methods: Rosiglitazone or ciglitazone were administered to male Wistar rats prior to and during reperfusion. Biochemical indicators of renal dysfunction and injury were measured and histological scoring of kidney sections was used to assess renal injury. Expression of PPAR isoforms and intercellular adhesion molecule-1 during renal I/R were assessed using RT-PCR and Northern blot, respectively. Myeloperoxidase activity and activation of poly(ADPribose) polymerase (PARP) were used as indicators of polymorphonuclear (PMN) cell infiltration and oxidative stress, respectively. Results: Expression of PPAR-alpha, PPAR-beta and PPAR-gamma1 (but not PPAR-gamma2) was observed in kidneys with down-regulation of PPAR-a expression during renal I/R. Rosiglitazone and ciglitazone significantly reduced biochemical and histological signs of renal dysfunction and injury. Renal expression of ICAM-1 caused by I/R was reduced by rosiglitazone and ciglitazone which was reflected by decreased PMN infiltration into reperfused renal tissues. Both rosiglitazone and ciglitazone reduced PARP activation indicating a reduction of oxidative stress. Conclusion: These results suggest that the PPAR-gamma agonists rosiglitazone and ciglitazone reduce the renal dysfunction and injury associated with I/R of the kidney. We propose that one mechanism underlying the protective effects involves inhibition of the expression of ICAM-1, a reduction of PMN infiltration into renal tissues and subsequent reduction of oxidative stress. Copyright (C) 2003 S. Karger AG, Basel.

AB - Background/Aims: Recent evidence indicates that peroxisome-proliferator activated receptor (PPAR) agonists protect against ischemia/reperfusion (I/R) injury. Here we investigate the effects of the PPAR-gamma agonists, rosiglitazone and ciglitazone, on the renal dysfunction and injury caused by I/R of the rat kidney in vivo. Methods: Rosiglitazone or ciglitazone were administered to male Wistar rats prior to and during reperfusion. Biochemical indicators of renal dysfunction and injury were measured and histological scoring of kidney sections was used to assess renal injury. Expression of PPAR isoforms and intercellular adhesion molecule-1 during renal I/R were assessed using RT-PCR and Northern blot, respectively. Myeloperoxidase activity and activation of poly(ADPribose) polymerase (PARP) were used as indicators of polymorphonuclear (PMN) cell infiltration and oxidative stress, respectively. Results: Expression of PPAR-alpha, PPAR-beta and PPAR-gamma1 (but not PPAR-gamma2) was observed in kidneys with down-regulation of PPAR-a expression during renal I/R. Rosiglitazone and ciglitazone significantly reduced biochemical and histological signs of renal dysfunction and injury. Renal expression of ICAM-1 caused by I/R was reduced by rosiglitazone and ciglitazone which was reflected by decreased PMN infiltration into reperfused renal tissues. Both rosiglitazone and ciglitazone reduced PARP activation indicating a reduction of oxidative stress. Conclusion: These results suggest that the PPAR-gamma agonists rosiglitazone and ciglitazone reduce the renal dysfunction and injury associated with I/R of the kidney. We propose that one mechanism underlying the protective effects involves inhibition of the expression of ICAM-1, a reduction of PMN infiltration into renal tissues and subsequent reduction of oxidative stress. Copyright (C) 2003 S. Karger AG, Basel.

KW - kidney

KW - reperfusion-injury

KW - renal dysfunction

KW - peroxisome-proliferator activated receptor rosiglitazone

KW - ciglitazone

KW - intercellular adhesion molecule-1

KW - ISCHEMIA-REPERFUSION INJURY

KW - CELL-ADHESION MOLECULES

KW - PPAR-GAMMA

KW - IN-VIVO

KW - FAILURE

KW - ROSIGLITAZONE

KW - RATS

KW - PROTECTS

KW - LIGAND

KW - PATHOPHYSIOLOGY

U2 - 10.1159/000072088

DO - 10.1159/000072088

M3 - Article

VL - 23

SP - 267

EP - 276

JO - American Journal of Nephrology

JF - American Journal of Nephrology

SN - 0250-8095

IS - 4

ER -