Riot control agent oleoresin capsicum triggers acute lung injury via TLR cascade independently of the TRPV1 pathway

抄録

Background: Oleoresin capsicum (OC) is used worldwide in the form of aerosolized spray or grenade as non-lethal riot control agent and self defence weaponry by women. The current study aims to demonstrate the pulmonary effects of inhaled OC by law enforcing agent at various concentrations and also to generate the prophylactic measures for the law enforcing personnel by targeting a transient receptor potential cation channel subfamily V member 1 (TRPV1) independent pathway.

Method: Female Wistar rats were used in the evaluation of respiratory dynamics and pulmonary function endpoints in a whole body plethysmograph (WBP) at 1h, 3h and 24 h post-exposure to OC. Blood, bronchoalveolar lavage fluid (BAL) and lung tissue were collected from the animals to evaluate biochemical parameters, inflammatory markers, oxidative stress and histopathology of the lungs respectively at 1, 3, and 24 h post OC exposure. Expressions of proteins targeting the toll like receptor (TLR) pathway were measured by western blotting and RT-PCR analysis.

Results: OC exposed rats demonstrated a decreased respiratory rate when measured by WBP. Acute exposure to OC induced production of excessive amounts of reactive oxygen species (ROS) eliciting oxidative stress damage that results in many pathophysiological processes. Leukocytosis was observed in the whole blood of the group exposed to the highest concentration of OC which might be due to tissue necrosis or infarction and confirmed by damage in the architecture of lungs in the same group. Our data further suggested that production of pro inflammatory markers may contribute to the lung's responses to acute oxidant-induced injury and inflammation. Futhermore, these effects were time dependent, reaching a maximum at 3 and 24 hours post exposure respectively. In addition, our study showed that OC exposure stimulated TLR4-dependent inflammatory genes and downstream signal molecules (i.e., MyD88, TRAF6, IRAK-1 etc.) in a concentration dependent manner.

Conclusion: Our study reports the unfavorable effects of OC through chemotactic and inflammatory mediators in the pulmonary system at concentrations used as mob dispersant. The current study for the first time reports the relation of effect of OC in lungs with the TLR cascade, a TRPV1 independent signaling pathway.