Glutamine Ameliorates Venom-induced Lung and Heart Injury Through HSP70: NF-κB P65 and P53/PUMA Signaling Pathways Involved

Overview

Journal J Venom Anim Toxins Incl Trop Dis

Date 2023 Jul 13

PMID 37441002

Authors

Yalan Li

Zhezhe Guan

Shaocong Hu

Zhi Huang

Dongling He

Xiaoyang Cheng

Tianlin Song

Caifeng Mo

Manqi Xiao

Yue Huang

Yuanmei Wei

Yi Zhou

Xuerong Zhang

Ming Liao

Affiliations

Soon will be listed here.

Abstract

Background: is one of the most dangerous venomous snakes prone to cardiopulmonary damage with extremely high mortality. In our previous work, we found that glutamine (Gln) and glutamine synthetase (GS) in pig serum were significantly reduced after bite. In the present study, to explore whether there is a link between the pathogenesis of cardiopulmonary injury and Gln metabolic changes induced by venom. We investigated the effect of Gln supplementation on the lung and heart function after snakebite.

Methods: We supplemented different concentrations of Gln to mice that were envenomated by to observe the biological behavior, survival rate, hematological and pathological changes. Gln was supplemented immediately or one hour after the venom injection, and then changes in Gln metabolism were analyzed. Subsequently, to further explore the protective mechanism of glutamine on tissue damage, we measured the expression of heat-shock protein70 (HSP70), NF-κB P65, P53/PUMA by western blotting and real-time polymerase in the lung and heart.

Results: Gln supplementation delayed the envenoming symptoms, reduced mortality, and alleviated the histopathological changes in the heart and lung of mice bitten by . Additionally, Gln increased the activity of glutamine synthetase (GS), glutamate dehydrogenase (GDH) and glutaminase (GLS) in serum. It also balanced the transporter SLC7A11 expression in heart and lung tissues. venom induced the NF-κB nuclear translocation in the lung, while the HO-1 expression was suppressed. At the same time, venom activated the P53/PUMA signaling pathway and the BAX expression in the heart. Gln treatment reversed the above phenomenon and increased HSP70 expression.

Conclusion: Gln alleviated the glutamine metabolism disorder and cardiopulmonary damage caused by venom. It may protect lungs and heart against venom by promoting the expression of HSP70, inhibiting the activation of NF-κB and P53/PUMA, thereby delaying the process of snake venom and reducing mortality. The present results indicate that Gln could be a potential treatment for bite.

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