AbstractBackground:Bungarus multicinctusis 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 afterBungarus
multicinctusbite. In the present study, to explore whether
there is a link between the pathogenesis of cardiopulmonary injury and Gln
metabolic changes induced byBungarus multicinctusvenom.
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
byBungarus multicinctusto 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 byBungarus multicinctus. 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.Bungarus
multicinctusvenom 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 byBungarus multicinctusvenom. 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 forBungarus multicinctusbite.