Melatonin attenuates LPS-induced pyroptosis in acute lung injury by inhibiting NLRP3-GSDMD pathway via activating Nrf2/HO-1 signaling axis.
Level 5 - mechanism / opinion, no new human data
Preclinical laboratory research (murine model and cell lines) with no human clinical data
PubMed 35468366 · doi:10.1016/j.intimp.2022.108782
What was done
Mice were pretreated with intraperitoneal melatonin (30 mg/kg) daily for 5 consecutive days before intratracheal LPS instillation. Human alveolar epithelial (A549) cells and murine macrophage (Raw264.7) cells were pretreated with melatonin (400 μM) before LPS (10 μg/ml) stimulation. Investigators assessed lung injury histology, edema, survival rates, oxidative stress markers (Nrf2, HO-1, NQO1, Mn-SOD, Catalase, ROS, MDA), inflammatory mediators (iNOS, TNF-α, IL-1β), and pyroptosis markers (NLRP3, Caspase-1, IL-18, GSDMD-N, LDH release, TUNEL staining).
What was found
The abstract reports directional findings without numerical values. Melatonin pretreatment reversed LPS-induced alveolar damage, neutrophil infiltration, pulmonary edema, and mortality in mice. In both in vivo and in vitro experiments, melatonin increased expression of antioxidant mediators (Nrf2, HO-1, NQO1, Mn-SOD, Catalase) and suppressed ROS, MDA, iNOS, TNF-α, and IL-1β. Melatonin also reversed LPS-induced upregulation of NLRP3, Caspase-1, IL-1β, IL-18, and GSDMD-N, and decreased LDH release and TUNEL-positive cells.
Why it matters
This study outlines a potential molecular pathway by which melatonin reduces oxidative stress and pyroptosis in preclinical acute lung injury models.
Limits
The study is restricted entirely to animal and in vitro models, without human clinical verification. Melatonin was administered solely as a prophylactic pretreatment rather than a post-injury treatment. Sample sizes and exact quantitative effect sizes are not reported in the abstract.
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