Abstract:
:Recently, we demonstrated that furosemide improves renal hemodynamics and attenuates ischemia/reperfusion (I/R)-associated changes in angiogenesis-related gene expression. However, the effect of furosemide on I/R-induced apoptosis is not known. We utilized a rat model of acute ischemic nephropathy to test the hypothesis that furosemide attenuates I/R-induced apoptosis. Male Sprague-Dawley rats anesthetized with urethane (50 mg/kg) were randomly allocated into four groups (n = 6 each): sham operated saline infusion, sham operated with furosemide (30 microg/kg/hr) infusion, unilateral renal ischemia (1 hr) followed by six hours of reperfusion, and I/R with furosemide infusion. Apoptosis was measured in kidney samples and compared between groups using ANOVA with Bonferroni correction. Apoptosis-related gene expression was assessed using microarray analysis and validated with RT-PCR. Phosphorylation of Akt was analyzed using ELISA, and data were compared between groups using the Mann Whitney U test. Compared to the control group, I/R significantly (p < 0.001) induced apoptosis in both the cortex and medulla. Similarly, microarray analysis revealed that I/R induced (< or = two-fold increase compared to control group) 73 apoptosis-related genes. Phosphorylation of Akt was significantly (p < 0.05) downregulated after I/R. Treatment with furosemide significantly (p < 0.001) reduced I/R-induced apoptosis in both the cortex and medulla and attenuated the expression of 72 I/R-induced apoptosis-related genes. Compared to the I/R group, furosemide significantly (p < 0.01) upregulated the phosphorylation of Akt. These data suggest that a low dose furosemide infusion may attenuate I/R-induced apoptosis and associated gene transcription, and imply a possible novel molecular basis for the mechanism of action of furosemide in acute renal failure.
journal_name
Ren Failjournal_title
Renal failureauthors
Aravindan N,Aravindan S,Riedel BJ,Weng HR,Shaw ADdoi
10.1080/08860220701263671subject
Has Abstractpub_date
2007-01-01 00:00:00pages
399-407issue
4eissn
0886-022Xissn
1525-6049pii
778551960journal_volume
29pub_type
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