Nephrol Dial Transplant (2001) 16: 1577-1582
© 2001 European Renal Association-European Dialysis and Transplant Association
Effect of mycophenolate mofetil on nitric oxide production and inducible nitric oxide synthase gene expression during renal ischaemia-reperfusion injury
1 Division of Nephrology and 2 Division of Medical Physics, University Department of Medicine, Queen Mary Hospital, Hong Kong
Background. Recent animal data suggest that inducible nitric oxide synthase (iNOS) derived nitric oxide (NO) plays an important role in the pathogenesis of renal ischaemia-reperfusion injury (IRI) and that inhibition of iNOS ameliorates IRI. Mycophenolate mofetil (MMF), a lymphocyte selective anti-proliferative agent, has been shown to inhibit NO production in vitro. The aim of this study is to evaluate the effect of MMF on NO production and iNOS gene expression in vivo during renal IRI.
Methods. Renal IRI was induced by clamping the left renal pedicle of male BALB/c mice for 30 min, followed by 15 min of reperfusion. The mice received placebo or MMF at 40, 80 or 120 mg/kg/day by oral gavage for 5 days before the operation. Sham-operated mice served as the operation control. The amount of NO produced and the level of iNOS gene expression in the kidney tissue during IRI was assessed by spin trapping electron paramagnetic resonance (EPR) spectroscopy and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) respectively.
Results. In the sham-operated kidneys, only low levels of NO and iNOS mRNA were detected. In mice with renal IRI, the amount of NO detected was significantly increased, which was reduced in a dose dependent fashion by pre-treatment with MMF. Pre-treatment with MMF also substantially reduced iNOS gene expression in the kidney tissue.
Conclusions. We conclude that pre-treatment with MMF inhibits the production of NO and the induction of iNOS gene expression in the kidney during IRI. These results suggest that MMF might have the potential to ameliorate renal IRI.
Keywords: ischaemia-reperfusion injury; mycophenolate mofetil; nitric oxide; renal
Correspondence and offprint requests to: Dr Sing Leung Lui, Division of Nephrology, University Department of Medicine, Queen Mary Hospital, Pokfulam, Hong Kong.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Kim, K. Y. Kim, H.-S. Jang, T. Yoshida, K. Tsuchiya, K. Nitta, J.-W. Park, J. V. Bonventre, and K. M. Park Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia-reperfusion injury in mouse kidney Am J Physiol Renal Physiol, March 1, 2009; 296(3): F622 - F633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Vermersch, T Stojkovic, and J de Seze Mycophenolate mofetil and neurological diseases Lupus, March 1, 2005; 14(3_suppl): s42 - s45. [Abstract] [PDF]
|
|
|
|
|
|
P. Vermersch, T. Stojkovic, and J. de Seze Mycophenolate mofetil and neurological diseases Lupus, January 1, 2005; 14(1_suppl): s42 - s45. [Abstract] [PDF]
|
|
|
|
 |
|
 F. A. Houssiau Management of Lupus Nephritis: An Update J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2694 - 2704. [Full Text] [PDF]
|
|
|
|
|
|
R. Zatz, I. L. Noronha, and C. K. Fujihara Experimental and clinical rationale for use of MMF in nontransplant progressive nephropathies Am J Physiol Renal Physiol, December 1, 2002; 283(6): F1167 - F1175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S L Lui, R Tsang, D Wong, K W Chan, T M Chan, P C W Fung, and K N Lai Effect of mycophenolate mofetil on severity of nephritis and nitric oxide production in lupus-prone MRL/lpr mice Lupus, July 1, 2002; 11(7): 411 - 418. [Abstract] [PDF]
|
|