Oxytocin maintains lung histological and functional integrity to confer protection in heat stroke

Cheng-Hsien Lin,Cheng-Chia Tsai,Hsi-Hsing Yang,Ching-Ping Chang,Tzu-Hao Chen

doi:10.1038/s41598-019-54739-1

Abstract

Oxytocin (OT) has been reported to have a protective effect in lipopolysaccharide-induced experimental acute lung injury (ALI). However, its role in heat stroke-related ALI has never been investigated. Herein, we aimed to explore the therapeutic effects and potential mechanism of action of OT on heat-induced ALI. Rats were treated with OT 60 min before the start of heat stress (42 °C for 80 min). Twenty minutes after the termination of heat stress, the effects of OT on lung histopathological changes, edema, acute pleurisy and the bronchoalveolar fluid levels of inflammatory cytokines and indicators of ischemia, cellular damage, and oxidative damage were assessed. We also evaluated the influence of OT pretreatment on heat-induced hypotension, hyperthermia, ALI score, and death in a rat model of heat stroke. The results showed that OT significantly reduced heat-induced lung edema, neutrophil infiltration, hemorrhage score, myeloperoxidase activity, ischemia, and the levels of inflammatory and oxidative damage markers in bronchoalveolar lavage fluid. The survival assessment confirmed the pathophysiological and biochemical results. An OT receptor antagonist (L-368,899) was administered 10 min before the OT injection to further demonstrate the role of OT in heat-induced ALI. The results showed that OT could not protect against the aforementioned heat stroke responses in rats treated with L-368,899. Interestingly, OT treatment 80 min after the start of heat shock did not affect survival. In conclusion, our data indicate that OT pretreatment can reduce the ischemic, inflammatory and oxidative responses related to heat-induced ALI in rats.

Highlights

Oxytocin (OT) has been reported to have a protective effect in lipopolysaccharide-induced experimental acute lung injury (ALI)
The percent survival was first analyzed to investigate the ability of OT pretreatment to reduce the lethality of experimental heat stroke
The beneficial effects of OT pretreatment were significantly reduced by L-368,899 treatment 10 min before OT injection, as demonstrated in L-368,899 + OT + heated rats (Fig. 1)

Summary

Introduction

Oxytocin (OT) has been reported to have a protective effect in lipopolysaccharide-induced experimental acute lung injury (ALI). Twenty minutes after the termination of heat stress, the effects of OT on lung histopathological changes, edema, acute pleurisy and the bronchoalveolar fluid levels of inflammatory cytokines and indicators of ischemia, cellular damage, and oxidative damage were assessed. Since heat stroke resembles LPS-induced sepsis in many aspects[15,16], OT pretreatment may protect against heat-induced ALI To address this hypothesis, we assessed the temporal profiles of edema (e.g., lung water content and Evans blue dye extravasation), acute pleurisy (e.g., exudate volume and polymorphonuclear [PMN] cell accumulation), and the levels of ischemia indicators (e.g., glutamate and lactate/pyruvate ratio), cellular damage indicators (e.g., glycerol and lactate dehydrogenase), inflammatory cytokines (e.g., tumor necrosis factor-alpha [TNF-α], interleukin-1β [IL-1β], IL-6, IL-10, and myeloperoxidase [MPO] activity), and oxidative damage indicators (e.g., nitric oxide [NO] and dihydroxybenzoic acid [DHBA]) in the bronchoalveolar fluid (BALF) of rats pretreated or post-treated with OT. The OT receptor antagonist (L-368,899) was given 10 min before OT to further demonstrate the role of OT in heat-induced ALI in rats[17]

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Discussion

Conclusion