Intraperitoneal Injection of Acetate Protects Mice Against Lipopolysaccharide (LPS)‑Induced Acute Lung Injury Through Its Anti-Inflammatory and Anti-Oxidative Ability

Abstract

Background As a member of short-chain fatty acids, acetate exhibits anti-inflammatory capacity. The present study aimed to investigate the effect of acetate on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explored its underlying mechanism. Material/Methods Acetate (250 mM, 400 μL) was given intraperitoneally 30 minutes after LPS (5 mg/kg) intratracheal injection. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected 6 hours after the challenge of LPS. The histopathology scores, wet-to-dry weight ratios, protein content, and cytokine levels in BALF were assessed. Results The acetate treatment resulted in improved lung pathological score, alleviated LPS-induced microvascular permeability, and suppressed the production of reactive oxygen species. Furthermore, acetate decreased the level of pro-inflammatory cytokines and chemokines in the lungs and BALF, consistent with the declined immune cell counting found in BALF. In addition, phosphorylation levels of mitogen-activated protein kinase (MAPK) pathway in lung tissues were downregulated by acetate. Conclusions These results suggested that acetate exerts its protective effects via anti-inflammatory and anti-oxidant activities on LPS-induced ALI.

Consecutive intra-gingival injections of lipopolysaccharide and butyric acid to mice induce abnormal behavior and changes in cytokine concentrations

“…In the present work, in both blood plasma and brain tissues of mice, an increase in the concentration of acetate was detected, even though, under normal circumstances, the concentration of acetate in circulation is low (e.g., 199.9 μmol/L in group C) [35]. Elsewhere, acetate has been found to be produced during endogenous bacterial fermentation in the gut as a protective response [36].…”

Potential Therapeutic Effects of Short-Chain Fatty Acids on Chronic Pain

“…A few studies have shown that acetate has anti-inflammatory effects [ 43 - 46 ], while direct evidence showing its role in pain modulation is lacking. The levels of acetic and propionate acids decrease remarkably in patients with inflammatory bowel disease compared to healthy individuals [ 47 ].…”

“…In a rat model of LPS-induced neuroinflammation, acetate supplementation exerts potent anti-inflammatory and neuroprotective effects by reducing pro-inflammatory cytokine expression and attenuating neuroglial activation [ 44 , 45 ]. Anti-inflammatory and anti-oxidative effects of acetate have been reported in an LPS-induced mouse model [ 46 ].…”

The Interaction of Microbiome and Pancreas in Acute Pancreatitis

“…Butyric acid reduces systemic inflammation by inhibiting the STAT1/AP1 signaling pathways in peritoneal macrophages, as well as the secretion of NLRP3 inflammasomes and pro-inflammatory factors [54]. Similarly, acetate alleviates the inflammatory response of the organism by exerting its antibacterial, anti-inflammatory, and antioxidant properties [109,110]. In addition, valproic attenuates AP by reducing myeloperoxidase activity and the local tissue destruction of other organs [111].…”