Effect of Oral Tributyrin Treatment on Lipid Mediator Profiles in Endotoxin-Induced Hepatic Injury.

Abstract

Eicosanoid modulation by butyrate has been reported in various cells and conditions. Recently, comprehensive analyses of lipid mediators using liquid chromatography/tandem mass spectrometry has been reported. We hypothesized that tributyrin, a prodrug of butyrate, may attenuate LPS-induced liver injury in rats by suppressing the production of pro-inflammatory lipid mediators and/or by inducing anti-inflammatory specialized proresolving mediators. To test this, groups of Wistar rats were orally administered tributyrin (1 g/kg body weight) or vehicle 1 h before intraperitoneal injection of LPS. The livers were collected at 0, 1.5, 6, and 24 h later and analyzed: lipid mediators were profiled by liquid chromatography/tandem mass spectrometry; expression of cyclooxygenase-2, 5-lipoxygenase (LOX), 12/15-LOX, and leukotriene (LT) A4 hydrolase, and nuclear translocation of 5-LOX were evaluated by western blot analysis; and induction of liver injury was assessed by immunostaining for 8-hydroxy-2'-deoxyguanosine, an indicator of oxidative DNA damage. We found that tributyrin treatment attenuated LPS-induced production of pro-inflammatory LTB4 (p < 0.05) and decreased oxidative stress levels in the liver. Tributyrin also attenuated the nuclear translocation of 5-LOX in response to LPS, suggesting a possible mechanism for the LTB4 reduction. LPS-induced changes in other lipid mediators were not significantly affected by tributyrin treatment up to 24 h after LPS injection. Our results suggest that oral tributyrin administration protects against endotoxemia-associated liver damage by reducing production of the pro-inflammatory eicosanoid LTB4.

• Authors: Makoto Miyoshi, Makoto Usami, Ayumi Kajita, Motoki Kai, Yuya Nishiyama, Masakazu Shinohara
• Journal: The Kobe journal of medical sciences (Kobe J Med Sci) Vol. 66 Issue 4 Pg. E129-E138 (Dec 16 2020) ISSN: 1883-0498 [Electronic] Japan
• PMID: 33994516 (Publication Type: Journal Article)

Chemical References

• Endotoxins
• Lipopolysaccharides
• Triglycerides
• Cyclooxygenase 2
• Epoxide Hydrolases
• tributyrin
• leukotriene A4 hydrolase

Topics

• Animals
• Chromatography, Liquid
• Cyclooxygenase 2 (genetics, metabolism, pharmacology)
• Endotoxins (metabolism, pharmacology)
• Epoxide Hydrolases
• Lipid Metabolism (drug effects)
• Lipidomics
• Lipopolysaccharides (administration & dosage, adverse effects)
• Liver (drug effects, metabolism)
• Oxidative Stress
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction
• Tandem Mass Spectrometry
• Triglycerides (administration & dosage, therapeutic use)