Protective Effect of Saroglitazar Against Acute Lung Injury Induced by LPS in Rats

Area of Science:

• Pulmonary Medicine
• Pharmacology
• Toxicology

Background:

• Sepsis-induced acute lung injury (ALI) is a critical condition with high mortality.
• Lipopolysaccharide (LPS) is a common inducer of ALI in experimental models.
• Identifying effective prophylactic agents for ALI is crucial.

Purpose of the Study:

• To investigate the prophylactic effects of saroglitazar (SAR) against LPS-induced ALI.
• To evaluate SAR's impact on lung pathology, inflammation, oxidative stress, and key molecular pathways.

Main Methods:

• Rats were pretreated with SAR (2 and 4 mg/kg) two weeks before LPS injection.
• Lung tissue injury, bronchoalveolar lavage fluid (BALF) analysis, and pulmonary molecular markers were assessed.
• Key pathways including oxidative stress, NF-κB, and inflammasome/pyroptosis signaling were examined.

Main Results:

• SAR pretreatment significantly alleviated LPS-induced lung pathological damage.
• SAR reduced inflammatory markers (TNF-α), oxidative stress (MDA, SOD, GSH), and key signaling molecules (NF-κB, IFN-β, SCG 3A2).
• SAR inhibited the activation of canonical and non-canonical inflammasomes and pyroptosis, evidenced by reduced NLRP3, Caspase-1, GSDMD, Caspase-11, and IL-1β.

Conclusions:

• Saroglitazar demonstrates significant prophylactic efficacy against LPS-induced ALI.
• SAR mitigates ALI by reducing inflammation, oxidative stress, and inflammasome/pyroptosis activation.
• SAR represents a potential therapeutic strategy for preventing sepsis-induced ALI.