Prednisolone has a positive effect on the kidney but not on the liver of brain dead rats: a potencial role in complement
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RESEARCH
Open Access
Prednisolone has a positive effect on the kidney but not on the liver of brain dead rats: a potencial role in complement activation Rolando Rebolledo1,2*† , Bo Liu1,3† , Mohammed Z Akhtar4 , Petra J Ottens1 , Jian-ning Zhang3 , Rutger J Ploeg1,4 and Henri GD Leuvenink1
Abstract Background: Contradictory evidence has been published on the effects of steroid treatments on the outcomes of kidney and liver transplantation from brain dead (BD) donors. Our study aimed to evaluate this disparity by investigating the effect of prednisolone administration on BD rats. Methods: BD induction was performed in ventilated rats by inflating a Fogarty catheter placed in the epidural space. Prednisolone (22.5 mg/kg) was administered 30 min prior to BD induction. After four hours of determination of BD: serum, kidney and liver tissues samples were collected and stored. RT-qPCR, routine biochemistry and immunohistochemistry were performed. Results: Prednisolone treatment reduced circulating IL-6 and creatinine plasma levels but not serum AST, ALT or LDH. Polymorphonuclear influx assessed by histology, and inflammatory gene expression were reduced in the kidney and liver. However, complement component 3 (C3) expression was decreased in kidney but not in liver. Gene expression of HSP-70, a cytoprotective protein, was down-regulated in the liver after treatment. Conclusions: This study shows that prednisolone decreases inflammation and improves renal function, whilst not reducing liver injury. The persistence of complement activation and the negative effect on protective cellular mechanisms in the liver may explain the disparity between the effects of prednisolone on the kidney and liver of BD rats. The difference in the molecular and cellular responses to prednisolone administration may explain the contradictory evidence of the effects of prednisolone on different organ types from brain dead organ donors. Keywords: Brain death, Organ donation, Steroids, Prednisolone, Kidney transplantation, Liver transplantation
Background The shortage of organs for transplantation remains one of the most important issues facing the transplant community today. Increasingly, organs from brain dead extended criteria donors (ECD) and donors after circulatory arrest (DCD) are being used to address the organ deficit. The short and long term outcomes of allografts obtained from these donors are inferior when compared to living donors *Correspondence: [email protected] † Equal contributors 1 Department of Surgery, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands 2 Department of Surgery, Faculty of Medicine, University of Chile, Independencia 1027, 8380453 Santiago, Chile Full list of author information is available at the end of the article
[1,2]. In the case of organs obtained from donors after brain death (DBD) it has been shown that HLA mismatched living donors have better outcomes even when cold ischemia times are taken into consideration [3]. The explanation for this lies in the process of
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