Dullemen, Leon van (2012) Donor pre-treatment with the heat shock protein-inducer geranylgeranylacetone reduces brain death-associated inflammation in the kidney at organ retrieval. thesis, Medicine.
Full text available on request.Abstract
Brain dead-derived kidney grafts have inferior transplantation outcomes compared to living donated kidneys. Factors leading to inferior organ quality are diminished organ perfusion and pro-inflammatory changes during the brain death period. The protective heat shock proteins (HSPs) are known to be up-regulated, but at the end of brain death. To reduce the brain death-related kidney injury, we want to increase the Hsp72 expression at the start of brain death. In this study we investigated whether geranylgeranylacetone (GGA), a Hsp72 inducer, can reduce the pro-inflammatory changes and improve kidney donor quality in an in vivo brain death rat model. Male F344 rats (275-300g, n=15) underwent slow induction of brain death and were kept brain dead for 4 hours. We administered GGA (400 mg/kg orally) or a saline vehicle 20h and 1h prior to brain death induction. Sham-operated animals (n=14) received the same treatment. At the moment of organ retrieval, the expressions of Hsp72 or other HSPs are not increased by GGA. However, kidney interleukin-6 (IL-6) mRNA levels in GGA pre-treated brain dead rats were lower compared to saline-treated controls. Systemic ASAT levels were also reduced by GGA, indicating decreased inflammation. These results suggest that GGA reduces pro-inflammation during the brain death period, despite the unchanged expression of Hsp72. To further explore the benefits of GGA on organ quality, we would need to transplant the GGA pre-treated brain death kidneys.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Leuvenink, H.G.D. and Department: and Surgical Research Lab, UMCG |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:04 |
| Last Modified: | 25 Jun 2020 11:04 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2444 |
Actions (login required)
 |
View Item |