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

Abstract

Effect of glucocorticoid administration on improving the outcomes of kidney and liver allografts has not been clearly elucidated. This study investigated the effect of prednisolone administration after onset of brain death (BD) on kidney and liver in a controlled rat model of BD. BD was induced in rats by inflating an epidurally placed balloon catheter. Animals were treated with saline or prednisolone (5, 12.5, or 22.5 mg/kg) one hour after the onset of BD. After 4 hours of BD, experiments were terminated and serum and tissues were collected. Tissue gene and protein expression were measured for markers of inflammation, apoptosis, and cellular stress response markers. Prednisolone caused a reduction of plasma levels of IL-6, while the tissue expression of IL-6, IL-1β, and MCP-1 in both kidney and liver were also reduced. Creatinine plasma levels, complement (C3) expression, HSP-70, HO-1, Bcl2/BAX ratio, and PMN influx did not significantly change in kidney nor liver. Plasma AST and LDH levels were increased in the prednisolone treated group. Our results demonstrate prednisolone can has an anti-inflammatory effect mediated through reducing serum circulating cytokines. However, this anti-inflammatory effect does not translate into improved kidney function and indeed was associated with increased liver injury markers.

Complement Therapeutics in the Multi-Organ Donor: Do or Don't?

“…ECD livers are vulnerable to hypoxia and tissue injury associated with DGF or graft survival. In order to improve the quality of these suboptimal liver grafts, several studies evaluated the effect of intervention during donor management, such as the administration of steroids, dopamine, and hormone replacement (10, 11, 53). Taken these data into account, the current strategies applied in LiTx have mainly been focusing on treatments to stabilize hemodynamic disorders associated with deceased donation.…”

“…Again, prednisolone reduced the levels of pro-inflammatory cytokine gene expression, but did not increase nor decrease the C3 expression compared to untreated DBD rats. These divergent C3 expressions after administration prednisolone are not fully understood, but could be explained by the fact that complement is involved in liver regeneration (11).…”

“…Still, continuing efforts to improve and preserve donor organs are important, for which interventions in the donor seem a promising strategy. During the last decade, several donor pretreatment interventions have been explored in both animal and human studies, like the effect of thyroid hormone treatment and steroid treatment (9–11). However, no consensus has been reached regarding these donor treatment strategies, due to inconsistent results (12).…”

Complement Activation in Liver Transplantation: Role of Donor Macrosteatosis and Implications in Delayed Graft Function

“…Studies in kidney transplantation have revealed that both brain and cardiac death significantly increase C3 expression and complement activation compared with living donors [ 152 , 153 , 154 , 155 ]. Administering steroids prior to transplantation has proved to be an effective anti-inflammatory treatment, although it does not appear to affect increased C3 expression in animal models of deceased donors [ 156 , 157 ]. The role of complement activation following brain death, and targeting complement to reduce transplant injury, have been well reviewed [ 158 ].…”

Estudo dos efeitos da solução salina hipertônica sobre a função e alterações do tecido cardíaco em modelo de morte encefálica em ratos

“…A administração de hormônio tireoidiano, por exemplo, mostra-se capaz de melhorar o estado metabólico e hemodinâmico 65-68 de animais em ME, porém esse resultado não se traduz em melhora clínica de potenciais doadores em uma metanálise 69 . Apesar dos corticoides não demonstrarem benefício em alguns estudos experimentais 70 104 , a ME produz alterações discretas na histologia cardíaca em ratos, que não são modificadas pelo bloqueio epidural. Estudos demostraram que a elevação da troponina-I sérica em potenciais doadores está relacionada ao pior prognóstico do transplante 41,43 .…”