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Int J Biochem Cell Biol ; 169: 106530, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38246263

RESUMEN

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has a high mortality rate and incidence of complications. The pathophysiology of ALI/ARDS is still not fully understood. The lipopolysaccharide (LPS)-induced mouse model of ALI has been widely used to study human ALI/ARDS. Sulfasalazine (SASP) has antibacterial and anti-inflammatory effects and is used for treating inflammatory bowel and rheumatic diseases. However, the effect of SASP on LPS-induced ALI in mice has not yet been reported. Therefore, we aimed to investigate the effect of SASP on LPS-induced ALI in mice. Mice were intraperitoneally injected with SASP 2 h before or 4 h after LPS modeling. Pulmonary pathological damage was measured based on inflammatory factor expression (malondialdehyde and superoxide dismutase levels) in the lung tissue homogenate and alveolar lavage fluid. The production of inflammatory cytokines and occurrence of oxidative stress in the lungs induced by LPS were significantly mitigated after the prophylactic and long-term therapeutic administration of SASP, which ameliorated ALI caused by LPS. SASP reduced both the production of inflammatory cytokines and occurrence of oxidative stress in RAW264.7 cells, which respond to LPS. Moreover, its mechanism contributed to the suppression of NF-κB and nuclear translocation. In summary, SASP treatment ameliorates LPS-induced ALI by mediating anti-inflammatory and antioxidant effects, which may be attributed to the inhibition of NF-κB activation and promotion of antioxidant defenses. Thus, SASP may be a promising pharmacologic agent for ALI therapy.


Asunto(s)
Lesión Pulmonar Aguda , Síndrome de Dificultad Respiratoria , Ratones , Humanos , Animales , FN-kappa B/metabolismo , Lipopolisacáridos/farmacología , Sulfasalazina/efectos adversos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Pulmón/patología , Estrés Oxidativo , Antiinflamatorios/farmacología , Citocinas/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/patología
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