The tryrosine inhibitor tyrphostin AG126 reduces renal ischemia/reperfusion injury in the rat.

P. K. Chatterjee, N. Patel, E. O. Kvale, Paul Anthony James Brown, Keith Nicol Stewart, D. Britti, S. Cuzzocrea, H. Mota-Filipe, C. Thiemermann

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background. We investigate the effects of tyrphostin AG126, an inhibitor of tyrosine kinase activity, on the renal dysfunction and injury caused by ischemia/reperfusion (I/R) of the kidney.

Methods. Tyrphostin AG126 (5 mg/kg intraperitoneally) was administered to male Wistar rats 30 minutes prior to bilateral renal ischemia for 45 minutes followed by reperfusion for up to 48 hours. Biochemical markers of renal dysfunction and injury were measured and renal sections assessed for renal injury. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and formation of nitrotyrosine and poly (ADP) ribose (PAR) were assessed using immunohistochemistry. Rat proximal tubular cells (PTCs) were incubated with interferon-gamma (100 IU/mL), bacterial lipopolysaccharide (10 mug/mL), and with increasing concentrations of tyrphostin AG126 (0.0001-1 mmol/L) for 24 hours. Nitric oxide production was measured in both plasma from rats subjected to I/R and in incubation medium from PTCs.

Results. After 6 hours of reperfusion, tyrphostin AG126 significantly reduced the increase in serum and urinary indicators of renal dysfunction and injury caused by I/R and reduced histologic evidence of renal injury. Tyrphostin AG126 also improved renal function (after 24 and 48 hours of reperfusion) and reduced the histologic signs of renal injury (after 48 hours of reperfusion). Tyrphostin AG126 reduced the expression of iNOS and nitric oxide levels in both rat plasma and in PTC cultures, as well as expression of COX-2. Tyrphostin AG126 also reduced nitrotyrosine and PAR formation, suggesting reduction of nitrosative stress and poly (ADP-ribose) polymerase (PARP) activation, respectively.

Conclusion. Taken together, these results show that tyrphostin AG126 significantly reduces the renal dysfunction and injury caused by I/R of the kidney. We propose that inhibition of tyrosine kinase activity may be useful against renal I/R injury.

Original languageEnglish
Pages (from-to)1605-1619
Number of pages14
JournalKidney International
Volume64
Issue number5
DOIs
Publication statusPublished - 2003

Keywords

  • kidney
  • reperfusion-injury
  • renal dysfunction
  • tubular injury
  • proximal tubular cells
  • inducible nitric oxide synthase
  • nitric oxide
  • cyclooxygenase-2
  • poly (ADP-ribose) polymerase
  • oxidative stress
  • peroxynitrite
  • nitrosative stress
  • NITRIC-OXIDE SYNTHASE
  • ISCHEMIA-REPERFUSION INJURY
  • NF-KAPPA-B
  • INDUCED LETHAL TOXICITY
  • CYCLOOXYGENASE-2 EXPRESSION
  • PROXIMAL TUBULE
  • PEROXYNITRITE FORMATION
  • SIGNAL-TRANSDUCTION
  • LIPOTEICHOIC ACID
  • CELL INJURY

Cite this

Chatterjee, P. K., Patel, N., Kvale, E. O., Brown, P. A. J., Stewart, K. N., Britti, D., ... Thiemermann, C. (2003). The tryrosine inhibitor tyrphostin AG126 reduces renal ischemia/reperfusion injury in the rat. Kidney International, 64(5), 1605-1619. https://doi.org/10.1046/j.1523-1755.2003.00254.x

The tryrosine inhibitor tyrphostin AG126 reduces renal ischemia/reperfusion injury in the rat. / Chatterjee, P. K.; Patel, N.; Kvale, E. O.; Brown, Paul Anthony James; Stewart, Keith Nicol; Britti, D.; Cuzzocrea, S.; Mota-Filipe, H.; Thiemermann, C.

In: Kidney International, Vol. 64, No. 5, 2003, p. 1605-1619.

Research output: Contribution to journalArticle

Chatterjee, PK, Patel, N, Kvale, EO, Brown, PAJ, Stewart, KN, Britti, D, Cuzzocrea, S, Mota-Filipe, H & Thiemermann, C 2003, 'The tryrosine inhibitor tyrphostin AG126 reduces renal ischemia/reperfusion injury in the rat.', Kidney International, vol. 64, no. 5, pp. 1605-1619. https://doi.org/10.1046/j.1523-1755.2003.00254.x
Chatterjee, P. K. ; Patel, N. ; Kvale, E. O. ; Brown, Paul Anthony James ; Stewart, Keith Nicol ; Britti, D. ; Cuzzocrea, S. ; Mota-Filipe, H. ; Thiemermann, C. / The tryrosine inhibitor tyrphostin AG126 reduces renal ischemia/reperfusion injury in the rat. In: Kidney International. 2003 ; Vol. 64, No. 5. pp. 1605-1619.
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abstract = "Background. We investigate the effects of tyrphostin AG126, an inhibitor of tyrosine kinase activity, on the renal dysfunction and injury caused by ischemia/reperfusion (I/R) of the kidney.Methods. Tyrphostin AG126 (5 mg/kg intraperitoneally) was administered to male Wistar rats 30 minutes prior to bilateral renal ischemia for 45 minutes followed by reperfusion for up to 48 hours. Biochemical markers of renal dysfunction and injury were measured and renal sections assessed for renal injury. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and formation of nitrotyrosine and poly (ADP) ribose (PAR) were assessed using immunohistochemistry. Rat proximal tubular cells (PTCs) were incubated with interferon-gamma (100 IU/mL), bacterial lipopolysaccharide (10 mug/mL), and with increasing concentrations of tyrphostin AG126 (0.0001-1 mmol/L) for 24 hours. Nitric oxide production was measured in both plasma from rats subjected to I/R and in incubation medium from PTCs.Results. After 6 hours of reperfusion, tyrphostin AG126 significantly reduced the increase in serum and urinary indicators of renal dysfunction and injury caused by I/R and reduced histologic evidence of renal injury. Tyrphostin AG126 also improved renal function (after 24 and 48 hours of reperfusion) and reduced the histologic signs of renal injury (after 48 hours of reperfusion). Tyrphostin AG126 reduced the expression of iNOS and nitric oxide levels in both rat plasma and in PTC cultures, as well as expression of COX-2. Tyrphostin AG126 also reduced nitrotyrosine and PAR formation, suggesting reduction of nitrosative stress and poly (ADP-ribose) polymerase (PARP) activation, respectively.Conclusion. Taken together, these results show that tyrphostin AG126 significantly reduces the renal dysfunction and injury caused by I/R of the kidney. We propose that inhibition of tyrosine kinase activity may be useful against renal I/R injury.",
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T1 - The tryrosine inhibitor tyrphostin AG126 reduces renal ischemia/reperfusion injury in the rat.

AU - Chatterjee, P. K.

AU - Patel, N.

AU - Kvale, E. O.

AU - Brown, Paul Anthony James

AU - Stewart, Keith Nicol

AU - Britti, D.

AU - Cuzzocrea, S.

AU - Mota-Filipe, H.

AU - Thiemermann, C.

PY - 2003

Y1 - 2003

N2 - Background. We investigate the effects of tyrphostin AG126, an inhibitor of tyrosine kinase activity, on the renal dysfunction and injury caused by ischemia/reperfusion (I/R) of the kidney.Methods. Tyrphostin AG126 (5 mg/kg intraperitoneally) was administered to male Wistar rats 30 minutes prior to bilateral renal ischemia for 45 minutes followed by reperfusion for up to 48 hours. Biochemical markers of renal dysfunction and injury were measured and renal sections assessed for renal injury. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and formation of nitrotyrosine and poly (ADP) ribose (PAR) were assessed using immunohistochemistry. Rat proximal tubular cells (PTCs) were incubated with interferon-gamma (100 IU/mL), bacterial lipopolysaccharide (10 mug/mL), and with increasing concentrations of tyrphostin AG126 (0.0001-1 mmol/L) for 24 hours. Nitric oxide production was measured in both plasma from rats subjected to I/R and in incubation medium from PTCs.Results. After 6 hours of reperfusion, tyrphostin AG126 significantly reduced the increase in serum and urinary indicators of renal dysfunction and injury caused by I/R and reduced histologic evidence of renal injury. Tyrphostin AG126 also improved renal function (after 24 and 48 hours of reperfusion) and reduced the histologic signs of renal injury (after 48 hours of reperfusion). Tyrphostin AG126 reduced the expression of iNOS and nitric oxide levels in both rat plasma and in PTC cultures, as well as expression of COX-2. Tyrphostin AG126 also reduced nitrotyrosine and PAR formation, suggesting reduction of nitrosative stress and poly (ADP-ribose) polymerase (PARP) activation, respectively.Conclusion. Taken together, these results show that tyrphostin AG126 significantly reduces the renal dysfunction and injury caused by I/R of the kidney. We propose that inhibition of tyrosine kinase activity may be useful against renal I/R injury.

AB - Background. We investigate the effects of tyrphostin AG126, an inhibitor of tyrosine kinase activity, on the renal dysfunction and injury caused by ischemia/reperfusion (I/R) of the kidney.Methods. Tyrphostin AG126 (5 mg/kg intraperitoneally) was administered to male Wistar rats 30 minutes prior to bilateral renal ischemia for 45 minutes followed by reperfusion for up to 48 hours. Biochemical markers of renal dysfunction and injury were measured and renal sections assessed for renal injury. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and formation of nitrotyrosine and poly (ADP) ribose (PAR) were assessed using immunohistochemistry. Rat proximal tubular cells (PTCs) were incubated with interferon-gamma (100 IU/mL), bacterial lipopolysaccharide (10 mug/mL), and with increasing concentrations of tyrphostin AG126 (0.0001-1 mmol/L) for 24 hours. Nitric oxide production was measured in both plasma from rats subjected to I/R and in incubation medium from PTCs.Results. After 6 hours of reperfusion, tyrphostin AG126 significantly reduced the increase in serum and urinary indicators of renal dysfunction and injury caused by I/R and reduced histologic evidence of renal injury. Tyrphostin AG126 also improved renal function (after 24 and 48 hours of reperfusion) and reduced the histologic signs of renal injury (after 48 hours of reperfusion). Tyrphostin AG126 reduced the expression of iNOS and nitric oxide levels in both rat plasma and in PTC cultures, as well as expression of COX-2. Tyrphostin AG126 also reduced nitrotyrosine and PAR formation, suggesting reduction of nitrosative stress and poly (ADP-ribose) polymerase (PARP) activation, respectively.Conclusion. Taken together, these results show that tyrphostin AG126 significantly reduces the renal dysfunction and injury caused by I/R of the kidney. We propose that inhibition of tyrosine kinase activity may be useful against renal I/R injury.

KW - kidney

KW - reperfusion-injury

KW - renal dysfunction

KW - tubular injury

KW - proximal tubular cells

KW - inducible nitric oxide synthase

KW - nitric oxide

KW - cyclooxygenase-2

KW - poly (ADP-ribose) polymerase

KW - oxidative stress

KW - peroxynitrite

KW - nitrosative stress

KW - NITRIC-OXIDE SYNTHASE

KW - ISCHEMIA-REPERFUSION INJURY

KW - NF-KAPPA-B

KW - INDUCED LETHAL TOXICITY

KW - CYCLOOXYGENASE-2 EXPRESSION

KW - PROXIMAL TUBULE

KW - PEROXYNITRITE FORMATION

KW - SIGNAL-TRANSDUCTION

KW - LIPOTEICHOIC ACID

KW - CELL INJURY

U2 - 10.1046/j.1523-1755.2003.00254.x

DO - 10.1046/j.1523-1755.2003.00254.x

M3 - Article

VL - 64

SP - 1605

EP - 1619

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 5

ER -