# Targeting mitochondrial apoptosis in septic lung injury: protective potential of omega-3 fatty acids

## TL;DR

Omega-3 fatty acids may protect lungs from sepsis-induced damage by reducing inflammation, oxidative stress, and mitochondrial cell death.

## Contribution

This study demonstrates the novel protective role of omega-3 fatty acids in sepsis-induced lung injury via mitochondrial apoptosis suppression.

## Key findings

- Omega-3 supplementation reduced histopathological lung damage and oxidative stress markers in septic rats.
- OM3 modulated pro-apoptotic and anti-apoptotic gene and protein expressions in LPS-induced lung injury.
- OM3 suppressed inflammation and mitochondrial apoptosis, suggesting therapeutic potential in sepsis.

## 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.