Abstract
Acute lung injury secondary to sepsis remains a major problem in critical patients. Lipopolysaccharide (LPS)-induced lung injury is characterized by inflammatory infiltration, oxidative stress, and extensive apoptosis, particularly via the mitochondrial pathway. Omega-3 (OM3) polyunsaturated fatty acids have been proposed as promising modulators of inflammation and oxidative damage. However, their role in regulating mitochondria-mediated apoptosis in sepsis remains underexplored. Thirty-two female Wistar albino rats were randomized into four groups: Control, LPS (5 mg/kg, i.p. 3th), LPS-OM3 (400 mg/kg/day, i.p., 3 day), and OM3 only. After 72 h, lung tissues were collected for histopathological scoring, immunohistochemistry as tumor necrosis factor-alpha (TNF-α), heat shock protein (HSP70), caspase-3 (Cas-3); biochemical analyses as total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and qRT-PCR for mitochondrial apoptosis markers B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cytochrome-c (Cyt-c) and Cas-9. LPS induced ALI characterized by bronchiolar epithelial degeneration, alveolar hemorrhage, inflammation, and hyaline membrane formation. Biochemically, TOS and OSI levels were significantly elevated, while TAS remained unchanged. Immunohistochemical and genetic analysis showed marked upregulation of TNF-α, HSP70, and Cas-3 Bax, Cyt-c, and Casp-9 expression and decreased Bcl-2 expression in the LPS group. OM3 supplementation significantly attenuated histopathological damage, reduced oxidative stress markers, suppressed immunopositivity of proinflammatory and apoptotic proteins, and favorably modulated the apoptosis-related gene expressions. OM3 fatty acids exert a potent protective effect against LPS-induced ALI by suppressing mitochondrial apoptosis, reducing oxidative stress, and modulating the inflammatory response. These findings highlight the therapeutic potential of OM3 in mitigating sepsis-associated pulmonary damage through mitochondrial preservation.