Inadequate anti-oxidative responses in kidneys of brain-dead rats.

INTRODUCTION: Brain death (BD)-related lipid peroxidation, measured as serum malondialdehyde (MDA) levels, correlates with delayed graft function (DGF) in renal transplant recipients. How BD affects lipid peroxidation is not known. The extent of BD-induced organ damage is influenced by the speed at which intracranial pressure increases. To determine possible underlying causes of lipid peroxidation, we investigated the renal redox balance by assessing oxidative and anti-oxidative processes in kidneys of brain-dead rats after fast and slow BD induction.

METHODS: BD was induced in 64 ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Fast and slow inductions were achieved by an inflation speed of 0.45 and 0.015 ml/min, respectively, until BD confirmation. Healthy non brain-dead rats served as reference values. Brain-dead rats were monitored for 0.5, 1, 2, or 4 hr(s) after which organs and blood were collected.

RESULTS: Increased MDA levels became evident at 2 hrs of slow BD induction at which increased superoxide levels, decreased GPx activity, decreased glutathione (GSH) levels, increased iNOS and HO-1 expression, and increased plasma creatinine levels were evident. At 4 hrs after slow BD induction, superoxide, MDA, and plasma creatinine levels increased further while GPx acitivity remained decreased. Increased MDA and plasma creatinine levels also became evident after 4 hrs fast BD induction.

CONCLUSION: BD leads to increased superoxide production, decreased GPx activity, decreased GSH levels, increased iNOS and HO-1 expression, and increased MDA and plasma creatinine levels. These effects were more pronounced after slow BD induction. Modulation of these processes could lead to decreased incidence of DGF.