Capmatinib Counteracts LPS-Induced Pulmonary and Testicular Injury Through Attenuating TLR4/NF-κB, PERK/PI3K, and Caspase-1/GSDMD Signaling Pathways.

Lipopolysaccharide (LPS)-mediated systemic inflammatory response accounts for the LPS pathogenicity in multi organs as lung and testis. LPS could cause a dysregulation of host response to infection, which may lead to life-threatening organ dysfunction. Accordingly, in our study, the probable protective impact of capmatinib against the LPS-induced acute inflammatory response was explored and the possible causal mechanisms were examined. Male Albino mice were pretreated with capmatinib (5 or 10 mg/kg, daily, orally) for 3 days then received single intraperitoneal injection of LPS (10 mg/kg) at day three. Capmatinib administration amended lung and testicular dysfunction as manifested by improved histopathological results and restored oxidant/antioxidant balance. Capmatinib effectively down-regulated protein kinase R-like endoplasmic reticulum kinase/phosphatidylinositol 3-kinase (PERK/PI3K) signaling pathway concomitant with toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) inflammatory pathway mitigation besides caspase-1/gasdermin D (GSDMD)-N-terminal pathway inhibition. Collectively, the current study emphasized that capmatinib had potential protective effect against LPS-induced pulmonary and testicular injury.