Interleukin-1 Receptor Antagonist Decreases Hypothalamic Oxidative Stress During Experimental Sepsis

In our previous work, we demonstrated that the intracerebroventricular (i.c.v.) injection of an interleukin-1 receptor antagonist (IL-1ra) prevented the impairment in vasopressin secretion and increased survival rate in septic rats. Additionally, we saw a reduction in nitric oxide (NO) levels in cer...

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Veröffentlicht in:Molecular neurobiology 2016-08, Vol.53 (6), p.3992-3998
Hauptverfasser: Wahab, Fazal, Santos-Junior, Nilton N., de Almeida Rodrigues, Rodrigo Pereira, Costa, Luis Henrique A., Catalão, Carlos Henrique R., Rocha, Maria Jose A.
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Sprache:eng
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Zusammenfassung:In our previous work, we demonstrated that the intracerebroventricular (i.c.v.) injection of an interleukin-1 receptor antagonist (IL-1ra) prevented the impairment in vasopressin secretion and increased survival rate in septic rats. Additionally, we saw a reduction in nitric oxide (NO) levels in cerebroventricular spinal fluid (CSF), suggesting that the IL-1ra prevents apoptosis that seems to occur in vasopressinergic neurons. Here, we investigated the effect of IL-1ra pre-treatment on the sepsis-induced increase in oxidative stress markers in the hypothalamus of rats. The animals were pre-treated by an i.c.v. injection of IL-1ra (9 nmol) or vehicle (0.01 M PBS) before being subjected to cecal ligation and puncture (CLP) or left as control (sham-operation or naive). After 4, 6, and 24 h, the animals were decapitated ( n  = 9/group) and the brain removed for hypothalamic tissue collection. Transcript and protein levels of IL-1, inducible nitric oxide synthase (iNOS), caspase-3, and hypoxia-inducible factor 1-alpha (HIF-1α) were measured by quantitative polymerase chain reaction (qPCR) and western blot, respectively. Hypothalamic mRNA levels of all these genes were significantly ( P  
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-015-9338-4