Korean J Nephrol.  2004 May;23(3):368-376.

Effect of Pretreatment of Mycophenolate Mofetil on Apoptotic Cell Death and Map Kinases Activation in Rat Kidneys with Ischemia/Reperfusion Injury

Affiliations
  • 1Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea. nephron@cmc.cuk.ac.kr

Abstract

BACKGROUND
This study was performed to investigate the effects of pretreatment of mycophenolate mofetil (MMF) on mitogen activated protein (MAP) kinase expression and apoptotic cell death in rat kidneys with ischemia/reperfusion (I/R) injury. METHODS: Three experiments were done separate ly, In the first experiment, the effect of MMF (20 or 60 mg/kg) on I/R injury was observed. In the second experiment, MAP kinase expression were observed according to the time interval after I/R injury. Finally, the effect of pretreatment of MMF (20 or 60 mg/kg) on I/R injury in terms of apoptotic cell death and MAP kinases were evaluated. We also studied pro-inflammatory cytokines (IL-1 and TNF-alpha) using PCR. RESULTS: BUN and Serum creatinine level in creased in rats with I/R injury but their levels were significantly decreased with MMF Pro-inflammatory cytokines (TNF-alpha & IL-1) and apoptosis-related gene (caspase-1 and caspase-3 activities) were also significantly decreased as compared with rats with I/R injury. Expressions of MAP kinase were significantly increased in kidneys with I/R injury compared with sham-operated control, but significantly decreased with MMF pretreatment. CONCLUSION: Pretreatment of MMF showed a significant decreases of apoptotic cell death, apoptosis-related genes, and MAP kinase expression. This may explain beneficial effect of MMF on subsequent I/R injury.

Keyword

Mycophenolate mofetil; Mitogen activated protein kinase; Ischemia-reperfusion injury; Apoptosis

MeSH Terms

Animals
Apoptosis
Caspase 3
Cell Death*
Creatinine
Cytokines
Kidney*
Phosphotransferases*
Polymerase Chain Reaction
Rats*
Reperfusion Injury
Caspase 3
Creatinine
Cytokines
Phosphotransferases
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