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Dr. Hussein Mohamed Elhusseiny Ali Elbayoumi :: Publications:

Title:
Tracking the therapeutic efficacy of a ketone mono ester and β-hydroxybutyrate for ulcerative colitis in rats: New perspectives
Authors: Osama A Mohammed, Sameh Saber, ......., Hussein M El-Husseiny, Mushabab Alghamdi, Mahmoud E Youssef
Year: 2024
Keywords: β-hydroxybutyrate, BD-AcAc 2, antioxiadant
Journal: Toxicology and Applied Pharmacology
Volume: 486
Issue: 116943
Pages: 116943
Publisher: Elsevier
Local/International: International
Paper Link:
Full paper Not Available
Supplementary materials Not Available
Abstract:

Ulcerative colitis (UC) is an inflammatory condition that affects the colon's lining and increases the risk of colon cancer. Despite ongoing research, there is no identified cure for UC. The recognition of NLRP3 inflammasome activation in the pathogenesis of UC has gained widespread acceptance. Notably, the ketone body β-hydroxybutyrate inhibits NLRP3 demonstrating its anti-inflammatory properties. Additionally, BD-AcAc 2 is ketone mono ester that increases β-hydroxybutyrate blood levels. It has the potential to address the constraints associated with exogenous β-hydroxybutyrate as a therapeutic agent, including issues related to stability and short duration of action. However, the effects of β-hydroxybutyrate and BD-AcAc 2 on colitis have not been fully investigated. This study found that while both exogenous β-hydroxybutyrate and BD-AcAc 2 produced the same levels of plasma β-hydroxybutyrate, BD-AcAc 2 demonstrated superior effectiveness in mitigating dextran sodium sulfate-induced UC in rats. The mechanism of action involves modulating the NF-κB signaling, inhibiting the NLRP3 inflammasome, regulating antioxidant capacity, controlling tight junction protein expression and a potential to inhibit apoptosis and pyroptosis. Certainly, BD-AcAc 2's anti-inflammatory effects require more than just increasing plasma β-hydroxybutyrate levels and other factors contribute to its efficacy. Local ketone concentrations in the gastrointestinal tract, as well as the combined effect of specific ketone bodies, are likely to have contributed to the stronger protective effect observed with ketone mono ester ingestion in our experiment. As a result, further investigations are necessary to fully understand the mechanisms of BD-AcAc 2 and optimize its use.

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