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2018 ; 15
(ä): 8
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Atorvastatin and diacerein reduce insulin resistance and increase disease
tolerance in rats with sepsis
#MMPMID29760586
da Silva KLC
; Camacho AP
; Mittestainer FC
; Carvalho BM
; Santos A
; Guadagnini D
; Oliveira AG
; Saad MJA
J Inflamm (Lond)
2018[]; 15
(ä): 8
PMID29760586
show ga
BACKGROUND: Sepsis is one of the leading causes of death among hospitalized
patients. At the onset of this condition, there is an over-production of
pro-inflammatory mediators that contribute to organ failure and death. The excess
production of pro-inflammatory mediators also impairs insulin signaling, which
may be a pathophysiological tissue marker of proinflammatory cytokine action
before organ failure. Statins and diacerein have pleiotropic effects, such as the
blockage of inflammatory signaling pathways, suggesting that these drugs may be
an attractive therapeutic or prophylactic strategy against sepsis. The aim of the
present study was to investigate whether a statin or diacerein can improve
insulin signaling, disease tolerance and survival in sepsis by inhibiting
inflammatory pathways. METHODS: We investigated the effect of these drugs on
survival, tissue insulin signaling and inflammatory pathways in the liver and
muscle of rats with sepsis induced by cecal ligation and puncture (CLP). RESULTS:
The results showed that administration of medications, with anti-inflammatory
ability, to septic animals increased survival and improved disease tolerance and
insulin resistance in the liver and muscle. The treatment also attenuated ER
stress, NF-?B, JNK activation and restored glucose-6-phosphatase (G6Pase) levels
in the liver. CONCLUSIONS: Our results indicate that atorvastatin and diacerein
treatment can modulate inflammatory pathways and, in parallel, attenuate insulin
resistance in sepsis. Since these two drugs have safety profiles and minimal side
effects, we suggest that these drugs may be alternative therapies for the
prevention or therapies for the treatment of insulin resistance in sepsis, which
could potentially reduce mortality in patients with sepsis.
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