Ethyl pyruvate ameliorates heat stroke-induced multiple organ dysfunction and inflammatory responses by induction of stress proteins and activation of autophagy in rats

Abstract

Objective: Heat stroke (HS) elicits the systemic inflammatory responses that result in multiple organ dysfunction (MOD). Heat shock response and autophagy are activated during heat stress for removal of damaged organelles and proteins, emerging as a major regulator of cellular homeostasis. Ethyl pyruvate (EP) is a derivative of pyruvic acid and possesses antioxidant and anti-inflammatory effects. This study aims to investigate the effects of EP on MOD in HS rats and explore the possible mechanisms. Method: Anesthetized rats were placed in a heating chamber (42 C) to elevate the core body temperature attaining to 42.9 C. Rats were then moved to room temperature and monitored for 6 h. EP (60 mg/kg, i.v.) was administered 30 min prior to heat exposure. Results: Results showed that EP significantly reduced HS-induced increases in plasma levels of LDH, CPK, GPT and CK-MB, reversed the decrease of platelet counts, and alleviated intestinal mucosal and pulmonary damage. Moreover, EP reduced pro-inflammatory protein, including TNF-a, IL-6, IL-1b, HMGB1 and iNOS, and induced stress proteins, heme oxygenase-1 (HO-1), heat shock protein (HSP) 70 and HSP90 in the liver of HS rats. The levels of HS-activated autophagy-regulatory proteins were affected by EP, in which the phosphorylated mTOR and AKT were reduced, and the phosphorylated AMPK increased, accompanied with upregulation in ULK1, Atg7, Atg12 and LC3II, and downregulation of p62. Conclusion:In conclusion, EP ameliorated HS-induced inflammatory responses and MOD, and the underlying mechanism is associated with the induction of the stress proteins HO-1 and HSP70 as well as restorage of autophagy.

Heat stress combined with lipopolysaccharide induces pulmonary microvascular endothelial cell glycocalyx inflammatory damage in vitro

“…33 IL-6 played a promoted role in development of inflammation, which was related to intracellular cascade signaling transduction induced by binding to specific receptors, and further magnified the effects of TNF-α. 34,35 Moreover, IL-6 played strong roles in promoting inflammation in the pathogenesis of MODS secondary to heat stroke. 35 vWF and ET-1 were associated with the function of promoting coagulation.…”

Heat stress combined with lipopolysaccharide induces pulmonary microvascular endothelial cell glycocalyx inflammatory damage in vitro

“…IL‐6 induced intracellular cascade signal transduction by binding to the IL‐6 receptor, which amplified the effect of TNF‐α and promoted the development of inflammation. promoted the development of inflammation 35,36 . Moreover, IL‐6 played a strong roles in promoting inflammation in the pathogenesis of MODS secondary to heat stroke 36 .…”

“…promoted the development of inflammation 35,36 . Moreover, IL‐6 played a strong roles in promoting inflammation in the pathogenesis of MODS secondary to heat stroke 36 . vWF and ET‐1 were associated with the function of promoting coagulation 37 .…”

“… 35 , 36 Moreover, IL‐6 played a strong roles in promoting inflammation in the pathogenesis of MODS secondary to heat stroke. 36 vWF and ET‐1 were associated with the function of promoting coagulation. 37 Endothelium was effective in constricting blood vessels via releasing ET‐1.…”

Heat shock Complicated by Acinetobacter baumannii Pneumonia

“…When the body is exposed to high temperatures, the synthesis of these proteins is induced to protect the body itself. They also play a crucial role in maintaining the stability of intracellular proteins by promoting protein folding and preserving the natural structure and function of various types of proteins, thus acting as the main regulators of cellular homeostasis [8][9] .…”