Immunopharmacology and immunotoxicology · 2025
Naftidrofuryl mitigates LPS-induced pulmonary injury through macrophage polarization and NLRP3/TLR4 regulation, an in vitro and in vivo perspective.
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Bahashwan Abdulrahman S, El-Shoura Ehab A M, Saad Hebatallah M, Zaafar Dalia
Аннотация
BACKGROUND: Acute lung injury (ALI) represents a diverse clinical condition characterized by significant complications and death rates. Naftidrofuryl (NAF) is a vasodilator drug with reported anti-inflammatory properties.
OBJECTIVE: This study aimed to explore the effects of NAF administration on lipopolysaccharide (LPS)-induced ALI through in vitro experiments using the human leukemia monocytic cell line (THP-1) and in vivo ALI-rat model, while investigating the potential underlying mechanisms.
METHODOLOGY: Inflammatory biomarkers for macrophage phenotypes were evaluated in vitro. Additionally, rats were classified into the following groups: Group I, Control, receiving daily intraperitoneal (ip) saline. Group II: NAF-treated rats (45 mg/kg/day, ip), Group III: LPS-treated rats (3 mg/kg, ip at day one), then continued with saline, Group IV: NAF+LPS-treated rats. This study lasted 28 days, after which the rats were sacrificed. Biochemical and histopathological analyses were conducted on pulmonary tissue.
RESULTS: The in vitro results highlighted the activation of macrophages from both phenotypes following LPS administration, indicating a disrupted macrophage environment characterized by altered levels of CD11b, CD38, CD206, IL-10, and LY6G/LY6C, as assessed by western blotting. NAF incorporation into LPS-treated samples significantly regulated all measured markers. The in vivo findings indicated an activated pro-inflammatory status, evidenced by elevated levels of TNF-α, IL-1β, IL-6, and iNOS in the LPS-treated group. The NLRP3/TLR4 pathway was activated, resulting in further disruption of redox and inflammatory homeostasis. Rats in Group-IV exhibited improved regulation of assessed parameters, characterized by decreased inflammation and modulation of the NLRP3/TLR4 pathway.
CONCLUSION: NAF may serve as a potential pulmonary protective agent against ALI by restoring inflammatory homeostasis and modulating various inflammatory pathways.
OBJECTIVE: This study aimed to explore the effects of NAF administration on lipopolysaccharide (LPS)-induced ALI through in vitro experiments using the human leukemia monocytic cell line (THP-1) and in vivo ALI-rat model, while investigating the potential underlying mechanisms.
METHODOLOGY: Inflammatory biomarkers for macrophage phenotypes were evaluated in vitro. Additionally, rats were classified into the following groups: Group I, Control, receiving daily intraperitoneal (ip) saline. Group II: NAF-treated rats (45 mg/kg/day, ip), Group III: LPS-treated rats (3 mg/kg, ip at day one), then continued with saline, Group IV: NAF+LPS-treated rats. This study lasted 28 days, after which the rats were sacrificed. Biochemical and histopathological analyses were conducted on pulmonary tissue.
RESULTS: The in vitro results highlighted the activation of macrophages from both phenotypes following LPS administration, indicating a disrupted macrophage environment characterized by altered levels of CD11b, CD38, CD206, IL-10, and LY6G/LY6C, as assessed by western blotting. NAF incorporation into LPS-treated samples significantly regulated all measured markers. The in vivo findings indicated an activated pro-inflammatory status, evidenced by elevated levels of TNF-α, IL-1β, IL-6, and iNOS in the LPS-treated group. The NLRP3/TLR4 pathway was activated, resulting in further disruption of redox and inflammatory homeostasis. Rats in Group-IV exhibited improved regulation of assessed parameters, characterized by decreased inflammation and modulation of the NLRP3/TLR4 pathway.
CONCLUSION: NAF may serve as a potential pulmonary protective agent against ALI by restoring inflammatory homeostasis and modulating various inflammatory pathways.