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A single dose of eHSP72 attenuates sepsis severity in mice.

ABSTRACT: High levels of extracellular 72?kDa heat shock protein (eHSP72) can be detected in the serum of septic patients and are associated with increased oxidative profiles and elevated rates of mortality among these patients. However, a possible immunomodulatory role for this protein, resulting in tissue protection during sepsis, has never been assessed. In this study, we investigated whether eHSP72 administration could attenuate the severity of sepsis in a mouse peritonitis model. Animals (90-day-old male C57BL/6J mice) were divided into Sepsis (n?=?8) and Sepsis?+?eHSP72 (n?=?9) groups, which both received injections of 20% fecal solution [1?mg/g body weight (wt), intraperitoneal (i.p.)], to trigger peritonitis induced-sepsis, whereas a Control group (n?=?7) received a saline injection. eHSP72 was administered (1.33?ng/g body wt) to the Sepsis+eHSP72 group, 12?h after sepsis induction. All animals were evaluated for murine sepsis score (MSS), hemogram, core temperature, and glycemia (before and 4, 12, and 24?h after sepsis induction). Treatment with eHSP72 promoted reduced sepsis severity 24?h after sepsis induction, based on MSS scores (Control?=?1.14?±?1.02; Sepsis?=?11.07?±?7.24, and Sepsis?+?eHSP72?=?5.62?±?1.72, P??0.05). Finally, eHSP72 improved the survival rate after sepsis (P?=?0.0371). Together, our results indicated that eHSP72 may ameliorate sepsis severity and possibly improve some sepsis indices in mice.

SUBMITTER: Sulzbacher MM

PROVIDER: S-EPMC7280184 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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A single dose of eHSP72 attenuates sepsis severity in mice.

Sulzbacher Maicon Machado MM Sulzbacher Lucas Machado LM Passos Felipe Rafael FR Bilibio Bruna Letícia Endl BLE Althaus Wellington Felipe WF Weizenmann Luana L de Oliveira Kauana K Frizzo Matias Nunes MN Ludwig Mirna Stela MS Heck Thiago Gomes TG

Scientific reports 20200608 1

High levels of extracellular 72 kDa heat shock protein (eHSP72) can be detected in the serum of septic patients and are associated with increased oxidative profiles and elevated rates of mortality among these patients. However, a possible immunomodulatory role for this protein, resulting in tissue protection during sepsis, has never been assessed. In this study, we investigated whether eHSP72 administration could attenuate the severity of sepsis in a mouse peritonitis model. Animals (90-day-old ...[more]

PMID: 32513986

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Project description:Introduction: Esketamine (Esk) (S(+)-ketamine) is now used as an alternative to its racemic mixture, i. e., ketamine in anesthesia. Esk demonstrated more powerful potency and rapid recovery in anesthesia and less psychotomimetic side effects comparing with ketamine, but Esk could still induce psychological side effects in patients. This study was to investigate whether dexmedetomidine (Dex) can attenuate the Esk-induced neuronal hyperactivities in Kunming mice. Methods: Dexmedetomidine 0.25, 0.5, and 1 mg/kg accompanied with Esk 50 mg/kg were administrated on Kunming mice to assess the anesthesia quality for 1 h. The indicators, such as time to action, duration of agitation, duration of ataxia, duration of loss pedal withdrawal reaction (PWR), duration of catalepsy, duration of righting reflex (RR) loss, duration of sedation, were recorded for 1 h after intraperitoneal administration. The c-Fos expression in the brain was detected by immunohistochemistry and Western Blot after 1 h of administration. Considering the length of recovery time for more than 1 h in Dex and Dex with Esk groups, other mice were repeatedly used to evaluate recovery time from the administration to emerge from anesthesia. Results: Dexmedetomidine dose-dependently increased recovery time when administrated with Esk or alone. Dex combined with Esk efficiently attenuated the duration of agitation, ataxia, and catalepsy. Dex synergically improved the anesthesia of Esk by increasing the duration of sedation, loss of RR, and loss of PWR. Esk induced the high expression of c-Fos in the cerebral cortex, hippocampus, thalamus, amygdala, hypothalamus, and cerebellum 1 h after administration. Western Blot results indicated that Dex at doses of 0.25, 0.5, and 1 mg/kg could significantly alleviate the Esk-induced c-Fos expression in the mice brain. Conclusion: Dexmedetomidine ranged from 0.25 to 1 mg/kg could improve the anesthesia quality and decreased the neuronal hyperactivities and the overactive behaviors when combined with Esk. However, Dex dose-dependently increased the recovery time from anesthesia. It demonstrated that a small dose of Dex 0.25 mg/kg could be sufficient to attenuate Esk-induced psychotomimetic side effects without extension of recovery time in Kunming mice.

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A single dose of eHSP72 attenuates sepsis severity in mice.

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A single dose of eHSP72 attenuates sepsis severity in mice.

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