Lipoxin A4 protects against paraquat-induced acute lung injury by inhibiting the TLR4/MyD88-mediated activation of the NF-κB and PI3K/AKT pathways

Paraquat (PQ) causes serious oxidative stress and inflammatory responses, particularly to the lungs. Since lipoxin A4 (LXA4) functions as an anti-inflammatory mediator, the present study aimed to explore its effects on PQ-induced acute lung injury (ALI) and to elucidate the possible underlying mechanisms. PQ was administered to male SD rats and RAW264.7 cells to establish a model of poisoning, and LXA4 was used as an intervention drug. LXA4 treatment attenuated PQ-induced lung injury, and this was accompanied by decreased tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta secretion levels, and reduced oxidative stress damage. Additionally, LXA4 treatment inhibited the activation of the inflammation-related signaling molecules, Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor (NF)-kappa B p65, p-phosphoinositide 3-kinase (PI3K) and p-AKT. Furthermore, the in vitro experiments further confirmed that the beneficial effects of LXA4 on PQ-induced damage were TLR4-dependent. Hence, the present study demonstrated that LXA4 attenuated PQ-induced toxicity in lung tissue and RAW264.7 macrophages, and that this protective effect may be closely related to the mitigation of inflammatory responses, oxidative stress damage and the TLR4/MyD88-mediated activation of the PI3K/AKT/NF-kappa B pathway.

Automated summary

The study demonstrated that LXA4 alleviated the effects of PQ-induced lung injury by reducing levels of inflammatory cytokines and oxidative stress damage, and inhibiting the activation of inflammation-related signaling molecules.