NIV Congres
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MnTMPyp, a selective superoxide dismutase mimetic, reduces oxidative stress in brain dead donors
Hoeksma, D., Dullemen, L.F.A. van, Ottens, P.J., Veldhuis, S., Ploeg, R.J., Leuvenink, H.G. D.
Categorie(ën):
Renal allografts retrieved from brain dead donors show inferior transplant outcomes compared to living donor grafts. Brain death (BD) leads to immunological activation and hemodynamic instability. Reactive oxygen species (ROS) are implicated in BD-induced organ damage. This study investigated whether pre-treatment with the free radical scavenger MnTMPyP reduces inflammation and renal injury in brain-dead organ donors.
BD was induced in male F344 rats (275-300g, n=7) by inflating a subdurally placed balloon catheter. Rats were treated with saline or MnTMPyP (5mg/kg) one hour before BD. After 4 hours of BD, serum and kidneys were collected. Sham-operated rats treated with saline or MnTMPyP served as controls. Malondialdehyde (MDA) levels, indicative for oxidative stress, were measured with the thiobarbituric acid (TBA) assay. Tissue gene expression was measured by Real Time qPCR. Tissue protein expression was detected by immunohistochemical analyses.
Pre-treatment of brain-dead donor organs with MnTMPyP significantly reduced serum MDA levels and renal expression of the stress protein HO-1. Interestingly, renal mRNA levels of HO-1 were increased. Furthermore, renal mRNA levels of TNF- α and E-selectin were decreased but not significantly.
This study shows that treatment of brain-dead donors with MnTMPyP is effective in reducing systemic oxidative stress.
- Over Hoeksma, D.
- Over Dullemen, L.F.A. van
- Over Ottens, P.J.
- Over Veldhuis, S.
- Over Ploeg, R.J.
- Over Leuvenink, H.G. D.