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

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 byEscherichia 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 (baseli ne)vs. T1 (post-LPS)  = 10 ± 1.2vs. 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 significantly positively correlated with IL-1β (R = 0.602,P = 0.001), IL-6 (R = 0.381,P = 0.033), and TNF-α (R = 0.514,P = 0.005) in 24 paired measurements. Compared to the LPS group, the LPS + Pro group...
Source: Inflammation - Category: Allergy & Immunology Source Type: research