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Opposite effects of prednisolone treatment on liver and kidney graft from brain dead rat donors
Rebolledo, R.A., Liu, M.D.B., Erp van, Ottens, P.J., Veldhuis, S., Leuvenink, H.G. D.
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Introduction Contradictory evidence has been published about utility of steroids in organ retrieval from brain dead (BD) donors. Therefore, this study investigated the effect of steroid treatment in the livers and kidneys of brain death rats.
Methods
BD was induced in rats by inflating a subdurally placed balloon catheter. Animals were treated with saline or prednisolone (22.5 mg/kg) one hour before BD. After 4 hours of BD, serum, kidneys and livers were collected. Sham-operated rats treated with saline or prednisolone served as controls. Tissue gene expression was measured by Real Time qPCR. Tissue protein expression was detected by immunohistochemical analyses.
Results After the BD period we found a significant reduction in plasma levels of IL-6 and creatinine, but not in AST, ALT and LDH after prednisolone treatment. Interestingly, polymorphonuclear influx was reduced in liver tissue but not in kidney samples from treated animals. Relative expression of inflammatory genes were significant down-regulated in liver and kidney (IL-6, TNF-a, IL-1b and MCP-1). Relative Complement (C3) expression was decreased in kidney but increased in liver after prednisolone treatment. The Bcl2/BAX ratio of the kidney and liver in BD animals was lower when compared to sham animals. Prednisolone treatment did not affect this ratio in BD animals. Curiously, a protective cellular gene like HSP-70 was down-regulated in the liver due to prednisolone treatment.
Discussion This study shows that pre-treatment of brain dead donors with prednisolone significantly reduces inflammation. This treatment improves renal function but does not reduce liver injury. This could be explained by the persistence of complement activation and a decrease of protective cellular mechanisms in the liver due to steroid treatment or it could be attributed to timing or dosing.
- Over Rebolledo, R.A.
- Over Liu, M.D.B.
- Over Erp van
- Over Ottens, P.J.
- Over Veldhuis, S.
- Over Leuvenink, H.G. D.