Basaal II - P51 - Inadequate upregulation of anti-oxidative mechanisms in brain-dead rat kidneys

D. Hoeksma, R. Rebolledo, C.M.V. Hottenrott, Y. Bodar, P. Ottens, J. Wiersema-Buist, H.G.D. Leuvenink

Chair(s): prof. dr. Eelco de Koning, LUMC

Thursday 10 march 2016

13:00 - 13:30h at Foyer

Categories: Postersessie

Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriƫen (klinisch, basaal, donatie)

Delayed graft function (DGF) remains a complication in renal transplant recipients. Brain death-related lipid peroxidation, an oxidative stress marker, is correlated with DGF. BD pathophysiology comprises ischemic, inflammatory, and metabolic changes which can all lead to oxidative stress. Furthermore, BD pathophysiology is influenced by the speed at which intracranial pressure (ICP) increases and therefore, oxidative and anti-oxidative processes could be influenced as well. Clinically, the speed at which ICP increases varies greatly among donors. To determine underlying causes of lipid peroxidation, we investigated oxidative and anti-oxidative processes in brain-dead rat kidneys after fast and slow BD induction.

BD was induced in male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Slow induction was achieved by inflating the catheter at a rate of 0.015ml/min and fast induction at a rate of 0.45ml/min. Rats were observed for 0.5h, 1h, 2h, or 4h. Kidneys were collected for analysis.

Both fast and slow induction led to increased superoxide levels, decreased glutathione peroxidase (GPx) activity, decreased GSH levels and increased iNOS, piGST, and HO-1 mRNA expression. These effects were more pronounced and persistent after slow induction. Additionally, the GSSG:GSH ratio was significantly increased after slow induction. After fast induction, GPx activity decreased but returned to baseline values.

BD leads to increased oxidant production and decreased anti-oxidative defenses which was more pronounced after slow induction. Modulation of superoxide, GPx activity, and GSH levels could decrease lipid peroxidation and lead to improved transplantation outcomes.