The Transient Receptor Potential Vanilloid 1 Antagonist Capsazepine Improves the Impaired Lung Mechanics during Endotoxemia

Abstract

Acute lung injury (ALI) caused by systemic inflammatory response remains a leading cause of morbidity and mortality in critically ill patients. Management of patients with sepsis is largely limited to supportive therapies, reflecting an incomplete understanding of the underlying pathophysiology. Furthermore, there have been limited advances in the treatments for ALI. In this study, lung function and a histological analysis were performed to evaluate the impact of transient receptor potential vanilloid-1 receptor (TRPV1) antagonist (capsazepine; CPZ) on the lipopolysaccharide (LPS)-induced lung injury in mice. For this, adult mice pre-treated with CPZ or vehicle received intraperitoneal injections of LPS or saline and 24 hr after, the mice were anaesthetized, and lung mechanics was evaluated. The LPS-challenged mice exhibited substantial mechanical impairment, characterized by increases in respiratory system resistance, respiratory system elastance, tissue damping and tissue elastance. The pre-treatment with CPZ prevented the increase in respiratory system resistance and decreased the increase in tissue damping during endotoxemia. In addition, mice pre-treated with CPZ had an attenuated lung injury evidenced by reduction on collapsed area of the lung parenchyma induced by LPS. This suggests that the TRPV1 antagonist capsazepine has a protective effect on lung mechanics in ALI during endotoxemia and that it may be a target for enhanced therapeutic efficacy in ALI.

Inflammation, Cancer and Immunity—Implication of TRPV1 Channel

“…In the studies by Ninomiya et al (41) pre-treatment of LPS-activated macrophages with TRPV1 antagonists AMG 9810 and CPZ reduced production of pro-inflammatory cytokines IL-6, IL-1β, and IL-18 and COX-2 expression. In mice, with LPS-induced lung injury, CPZ pre-treatment prevented the increase in respiratory system resistance, tissue damping, and decreased the area of collapsed lung parenchyma (42).…”

C-Fiber Degeneration Enhances Alveolar Macrophage-Mediated IFN-α/β Response to Respiratory Syncytial Virus

“…The TRPV1 receptor antagonist capsazepine (CPZ) (MedChemExpress, HY-15640) and CAP were each dissolved in a solution containing 0.9% NaCl, Tween 80, and ethanol at a ratio of 8:1:1. CPZ (dose of 15 mg/kg) and CAP (dose of 1 mg/kg) were administered by subcutaneous (s.c.) injection ( 59 ). Within 30 min, the mice were intranasally (i.n.)…”

Comparative effects of capsaicin in chronic obstructive pulmonary disease and asthma (Review)

“…One of the frequently studied TRPV1 antagonists is capsazepine. Capsazepine is a specific antagonist of capsaicin-induced C-fiber activation and has been used to uncover additional roles of the TRPV1 receptor, specifically, its involvement in the onset of clinical respiratory symptoms (57)(58)(59).…”