Prednisolone has a positive effect on the kidney but not on the liver of brain dead rats: a potencial role in complement activation

Abstract

BackgroundContradictory 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.MethodsBD 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.ResultsPrednisolone 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.ConclusionsThis 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.

Steroid Anti-Inflammatory Effects Did Not Improve Organ Quality in Brain-Dead Rats

“…Induction of brain death showed a consistent and uniform pattern in blood pressure with a mean induction time of 32,5 ± 2,5 minutes which is similar to our previous publications [ 31 ]. After brain death induction all animals were kept with a mean arterial pressure of above 80 mmHg during the remainder of the experiment ( Figure 1 ).…”

“…In a previous study we showed that prednisolone administered before the induction of brain death in fact reduced inflammation measured by IL-6 plasma levels and renal and liver expression of proinflammatory cytokines like IL-6, IL-1β, MCP-1 , and TNF-α . Interestingly prednisolone pretreatment did improve renal function measured by creatinine plasma levels but did not improve liver cellular injury measured by AST, ALT, and LDH plasma levels [ 31 ]. We think that this differing effect may be related with the persistence of complement activation ( C3 ) in the liver and downregulation of protective cellular mechanisms such as heat shock proteins.…”

“…In previous studies we have shown that following the onset of BD apoptosis is increased in both the liver and kidney [ 27 , 31 ]. However, apoptosis seems to be triggered independently of the systemic inflammatory response, perhaps by other factors such as cellular stress, hypoxia, and altered metabolism.…”

“…We hypothesised that prednisolone treatment administered after brain death induction could reduce the inflammatory response in brain-dead rats and improve kidney function but not liver cellular injury based on our previous work [ 31 ].…”

Steroid minimization immunosuppression protocol using basiliximab in adult living donor liver transplantation for hepatitis C virus‐related cirrhosis

“…Intraportal infusion of steroids and prostaglandin E1 administrated for ABO incompatible cases during the first 2 weeks after transplantation could have played a role; however, the sample size was very small to draw a definite conclusion. Prostaglandin E1 is a potent vasodilator and may potentially protect the kidney; however, the positive effect of steroids on kidney function has been shown in only animal studies at the time of writing …”