Effects of Beta-Hydroxybutyrate on H₂O₂-Induced Inflammation in AC16 Cardiomyocytes

Year 2025, Volume: 55 Issue: 3, 419 - 426, 14.01.2026

Berna Güven

https://doi.org/10.26650/IstanbulJPharm.2025.1508683

https://izlik.org/JA83PD83JS

Abstract

Background and Aims: Systemic and local inflammation appear to play an important role in the development and progression of cardiovascular disease. A cause of myocardial damage is inflammation, which can be detected by the elevation of certain proteins. Targeting inflammation in cardiovascular disease is therefore an alternative approach to treatment.

Methods: The inflammatory effects of hydrogen peroxide (H₂O₂) were initially investigated using a human cardiomyocyte cell line (AC16). In this context, the optimal inflammatory H₂O₂ concentration (200 μM) was determined through the MTT assay. Then, the cells were incubated with/without H₂O₂ and treated with two different concentrations of beta-hydroxybutyrate (βOHB, 2 mM/10 mM). The protein expression levels of nod-like receptor protein 3 (NLRP3), tumour necrosis factor-α (TNF-α), nuclear factor-κB (NF- κB), and mitochondrial transcription factor A (TFAM) were evaluated via Western blotting to investigate the impact of βOHB treatment on inflammation and mitochondrial function.

Results: The results demonstrated that βOHB at a concentration of 2 mM did not significantly alter the levels of the inflammatory proteins. However, at 10 mM, βOHB significantly reduced the expression levels of NLRP3 and TNF-α. Furthermore, the expression of TFAM was significantly altered only in control cells that had not been exposed to H₂O₂, suggesting a potential effect of βOHB on mitochondrial function under baseline conditions.

Conclusion: βOHB has the potential to prevent the increase in the inflammatory response in a dosedependent manner and may influence mitochondrial function in cardiomyocytes.

Keywords

βOHB , Cardiac cell , Inflammation , Ketone bodies , Mitochondria , NLRP3

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