Novel Properties of Old Propranolol─Assessment of Antiglycation Activity through <i>In Vitro</i> and <i>In Silico</i> Approaches

Lauko, Kamil Klaudiusz; Nesterowicz, Miłosz; Trocka, Daria; Dańkowska, Karolina; Żendzian-Piotrowska, Małgorzata; Zalewska, Anna; Maciejczyk, Mateusz

doi:10.1021/acsomega.4c03025

Cited by 2 publications

References 107 publications

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Methylglyoxal is an antibacterial effector produced by macrophages during infection

Anaya-Sanchez,

Berry,

Espich

et al. 2024

Preprint

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Infected macrophages transition into aerobic glycolysis, a metabolic program crucial for control of bacterial infection. However, antimicrobial mechanisms supported by aerobic glycolysis are unclear. Methylglyoxal is a highly toxic aldehyde that modifies proteins and DNA and is produced as a side-product of glycolysis. Here we show that despite the toxicity of this aldehyde, infected macrophages generate high levels of methylglyoxal during aerobic glycolysis while downregulating the detoxification system. We use targeted mutations in mice to modulate methylglyoxal generation and show that reducing methylglyoxal production by the host promotes survival of Listeria monocytogenes and Mycobacterium tuberculosis, whereas increasing methylglyoxal levels improves control of bacterial infection. Furthermore, we show that bacteria that are unable to detoxify methylglyoxal are avirulent and experience up to 1000- fold greater genomic mutation frequency during infection. Taken together, these results suggest that methylglyoxal is an antimicrobial innate immune effector that defends the host against bacterial pathogens.

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Methylglyoxal is an antibacterial effector produced by macrophages during infection

Anaya-Sanchez,

Berry,

Espich

et al. 2024

Preprint

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β-blockers and metabolic modulation: unraveling the complex interplay with glucose metabolism, inflammation and oxidative stress

Drygała,

Radzikowski,

Maciejczyk

2024

Front. Pharmacol.

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The growing burden of metabolic disorders manifested by hypertension, type 2 diabetes mellitus, hyperlipidemia, obesity and non-alcoholic fatty liver disease presents a significant global health challenge by contributing to cardiovascular diseases and high mortality rates. Β-blockers are among the most widely used drugs in the treatment of hypertension and acute cardiovascular events. In addition to blocking the receptor sites for catecholamines, third-generation β-blockers with associated vasodilating properties, such as carvedilol and nebivolol, provide a broad spectrum of metabolic effects, including anti-inflammatory and antioxidant properties and a favorable impact on glucose and lipid metabolism. This review aims to report the impact of β-blockers on metabolic modulation based on available literature data. We present an overview of β-blockers and their pleiotropic properties, discuss mechanisms by which these drugs affect cellular metabolism and outline the future perspectives. The influence of β-blockers on glucose metabolism, insulin sensitivity, inflammation and oxidative stress is complex and varies depending on the specific β-blocker used, patient population and underlying health conditions. Recent evidence particularly highlights the potential role of vasodilatory and nitric oxide-mediated properties of nebivolol and carvedilol in improving glycemic control, insulin sensitivity, and lipid metabolism and mitigating oxidative stress and inflammation. It suggests that these drugs may be potential therapeutic options for patients with metabolic disorders, extending beyond their primary role in cardiovascular management.

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Novel Properties of Old Propranolol─Assessment of Antiglycation Activity through In Vitro and In Silico Approaches

Cited by 2 publications

References 107 publications

Methylglyoxal is an antibacterial effector produced by macrophages during infection

Methylglyoxal is an antibacterial effector produced by macrophages during infection

β-blockers and metabolic modulation: unraveling the complex interplay with glucose metabolism, inflammation and oxidative stress

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