The Pannexin-1 Channel Inhibitor Probenecid Attenuates Skeletal Muscle Cellular Energy Crisis and Histopathological Injury in a Rabbit Endotoxemia Model

Inflammation
Huaiwu HeBo Yao

Abstract

This study aimed to investigate the effect of probenecid (Pro) as an inhibitor of the pannexin-1 (Panx-1) channel-mediated release of intracellular ATP to the extracellular compartment on inflammation, cellular energy crisis, and organ injury in a rabbit sepsis model induced by Escherichia coli lipopolysaccharides (LPS). A total of 24 anesthetized and ventilated rabbits were randomly assigned to receive one of four treatments: infusion of LPS without Pro (LPS group), infusion of LPS with Pro (LPS + Pro group), sham operation without Pro (normal group), and sham operation with Pro (normal + Pro group). The LPS group had significantly higher serum ATP levels, serum inflammatory factor levels (TNF-α, IL-6, and IL-1β), and lower ATP concentrations and ATP/ADP ratios in the skeletal muscle tissue than the normal group. Compared to that at baseline, the expression of Panx-1 in peripheral blood cells increased significantly after the infusion of LPS (fluorescence intensity of Panx-1: T0 (baseline) vs. T1 (post-LPS) = 10 ± 1.2 vs. 84 ± 48, P < 0.0001; paired differences 73 ± 46, P = 0.024). Moreover, the LPS group exhibited higher expression of Panx-1 in the skeletal muscle tissue than the normal group. The serum ATP level was signific...Continue Reading

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Citations

Jun 13, 2021·Cardiovascular Research·Zsófia OnódiZoltán V Varga

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Methods Mentioned

BETA
enzyme-linked immunoadsorbent assay
electrophoresis
light microscopy

Software Mentioned

SPSS
Image Quant TL
ZEN microscope

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