The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice.
The corticosteroid compounds prednisolone and vamorolone do not alter the nociception phenotype and exacerbate liver injury in sickle cell mice.
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DOI：
10.1038/s41598-018-24274-6
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发表时间：
2018-04-17
影响因子：
4.6
通讯作者：
Quezado ZMN
中科院分区：
文献类型：
--
作者：
Almeida LEF;Damsker JM;Albani S;Afsar N;Kamimura S;Pratt D;Kleiner DE;Quezado M;Gordish-Dressman H;Quezado ZMN
临床医生经常犹豫是否开具皮质类固醇处方来治疗镰状细胞病（SCD）患者的皮质类固醇反应性疾病，因为其使用可能与并发症（增加的再入院率、反跳痛、中风、缺血性坏死、急性胸部综合征）相关。因此，SCD患者可能会接受次优的皮质类固醇反应性疾病治疗。我们进行了一项临床前试验的解离（vamorolone）和传统的（泼尼松龙）皮质类固醇化合物，以评估其对伤害感受表型，炎症和器官功能障碍的SCD小鼠的影响。泼尼松龙和vamorolone对纯合子小鼠的伤害感受表型或贫血没有显著影响。相反，泼尼松龙和vamorolone显着降低白色血细胞计数和肝脏炎症。有趣的是，由于与泼尼松龙相比，瓦莫龙产生的肝脏炎症衰减较少，因此瓦莫龙的作用比泼尼松龙的作用更温和。与对照组和杂合子相比，纯合子有显著的肝坏死，尽管肝脏炎症减少，但泼尼松龙和瓦莫龙显著加重了肝坏死。这些肝组织病理学变化与转氨酶和碱性磷酸酶升高相关。总之，这些结果表明，即使在肝脏炎症减少的情况下，泼尼松龙和伐莫龙也与SCD小鼠的显著肝毒性相关。这些发现提高了在SCD中使用皮质类固醇（常规和分离）可能发生肝功能恶化的可能性。
Clinicians often hesitate prescribing corticosteroids to treat corticosteroid-responsive conditions in sickle cell disease (SCD) patients because their use can be associated with complications (increased hospital readmission, rebound pain, strokes, avascular necrosis, acute chest syndrome). Consequently, SCD patients may receive suboptimal treatment for corticosteroid-responsive conditions. We conducted a preclinical trial of dissociative (vamorolone) and conventional (prednisolone) corticosteroid compounds to evaluate their effects on nociception phenotype, inflammation, and organ dysfunction in SCD mice. Prednisolone and vamorolone had no significant effects on nociception phenotype or anemia in homozygous mice. Conversely, prednisolone and vamorolone significantly decreased white blood cell counts and hepatic inflammation. Interestingly, the effects of vamorolone were milder than those of prednisolone, as vamorolone yielded less attenuation of hepatic inflammation compared to prednisolone. Compared to controls and heterozygotes, homozygotes had significant liver necrosis, which was significantly exacerbated by prednisolone and vamorolone despite decreased hepatic inflammation. These hepatic histopathologic changes were associated with increases in transaminases and alkaline phosphatase. Together, these results suggest that, even in the setting of decreasing hepatic inflammation, prednisolone and vamorolone were associated with significant hepatic toxicity in SCD mice. These findings raise the possibility that hepatic function deterioration could occur with the use of corticosteroids (conventional and dissociative) in SCD.
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DOI：
10.1016/j.niox.2011.12.004
发表时间：
2012-02-15
期刊：
Nitric oxide : biology and chemistry
影响因子：
--
作者：
Finkel J;Guptill V;Khaibullina A;Spornick N;Vasconcelos O;Liewehr DJ;Steinberg SM;Quezado ZM
通讯作者：
Quezado ZM
影响因子：
5.5
作者：
Lanaro, C.;Franco-Penteado, C. F.;Costa, F. F.
通讯作者：
Costa, F. F.
影响因子：
20.3
作者：
Ballas, Samir K.;Gupta, Kalpna;Adams-Graves, Patricia
通讯作者：
Adams-Graves, Patricia
影响因子：
3.7
作者：
Allareddy, Veerajalandhar;Roy, Aparna;Rotta, Alexandre T.
通讯作者：
Rotta, Alexandre T.
影响因子：
20.3
作者：
Bernini, JC;Rogers, ZR;Buchanan, GR
通讯作者：
Buchanan, GR