Dantrolene is an HDL-associated paraoxonase-1 activator with immunosuppressive and atheroprotective properties

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2025, Volume and Issue: 1870(2), P. 159596 - 159596

Published: Jan. 21, 2025

Language: Английский

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Antioxidant and Anti-Inflammatory Functions of High-Density Lipoprotein in Type 1 and Type 2 Diabetes

Antioxidants, Journal Year: 2023, Volume and Issue: 13(1), P. 57 - 57

Published: Dec. 28, 2023

(1) Background: high-density lipoproteins (HDLs) exhibit antioxidant and anti-inflammatory properties that play an important role in preventing the development of atherosclerotic lesions possibly also diabetes. In turn, both type 1 diabetes (T1D) 2 (T2D) are susceptible to having deleterious effects on these HDL functions. The objectives present review expound upon functions HDLs setting cardiovascular diseases discuss contributions onset (2) Methods: this narrative is based literature available from PubMed database. (3) Results: several HDLs, such as paraoxonase-1 activity, compromised T2D, thereby facilitating pro-atherogenic oxidized low-density lipoproteins. addition, diminished ability inhibit pro-inflammatory pathways vessels individuals with T2D. Although less extensive, recent evidence suggests defective antiatherogenic particles T1D. Lastly, substantial indicates a by modulating glucose metabolism. (4) Conclusions perspectives: impaired intriguing targets for mitigating risk Further investigations needed clarify influence glycaemic control nephropathy functionality patients Furthermore, exploring novel antidiabetic drugs used management T2D may provide insights future research.

Language: Английский

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The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2962 - 2962

Published: March 4, 2024

The incidence and prevalence of cardiovascular diseases are still rising. principal mechanism that drives them is atherosclerosis, an affection given by dyslipidemia a pro-inflammatory state. Paraoxonase enzymes have protective role due to their ability contribute antioxidant anti-inflammatory pathways, especially paraoxonase 1 (PON1). PON1 binds with HDL (high-density lipoprotein), high serum levels lead state against dyslipidemia, diseases, diabetes, stroke, nonalcoholic fatty liver disease, many others. Modulating expression might be treatment objective significant results in limiting the atherosclerosis. Lifestyle including diet exercise can raise its levels, some beneficial plants been found influence levels; therefore, more studies on herbal components needed. Our purpose highlight roles Praoxonase 1, implications other emphasize modulate expression, targeting potential flavonoids could introduced as supplements our validate hypothesis any effects regarding function.

Language: Английский

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White adipose tissue, a novel antirheumatic target: Clues from its secretory capability and adipectomy‐based therapy

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 181(16), P. 2774 - 2793

Published: April 21, 2024

Abstract Background and Purpose White adipose tissue (WAT) is involved in rheumatoid arthritis (RA). This study explored its potential as an antirheumatic target. Experimental Approach WAT status of healthy adjuvant‐induced (AIA) rats were compared. The contribution to RA pathology was evaluated by pre‐adipocyte transplant experiments dissecting perirenal fat pads AIA rats. impact on investigated culturing pre‐adipocytes. Proteins differentially expressed identified the UPLC/MS 2 method. These together with PPARγ siRNA agonist used treat pre‐adipocytes vitro. medium for THP‐1 monocyte culture. Key Results Compared controls, smaller but secreted more leptin, eNAMPT, MCP‐1, TNF‐α, IL‐6. rat increased levels these adipokines recipients. patients' serum induced a similar secretion change impaired differentiation Adipectomy eased AIA‐related immune abnormalities arthritic manifestations. Hepatokines PON1, IGFBP4, GPIHBP1 among differential proteins high blood, inflammatory secretions inhibited expression caused impairment pre‐adipocytes, outcome PPARγ‐silencing. endowed cells ability activate monocytes, which can be abrogated rosiglitazone. Conclusion Implications Certain hepatokines potentiate expedite progression inhibiting PPARγ. Targeting this signalling or abnormal various approaches may reduce severity.

Language: Английский

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The Role of ‘Paraoxonase-1 Activity’ as an Antioxidant in Coronary Artery Diseases

JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH, Journal Year: 2013, Volume and Issue: unknown

Published: Jan. 1, 2013

A majority of the Coronary Artery Diseases (CAD) result from complications atherosclerosis. There is a growing body evidence which has revealed that reduced activity HDL-associated enzyme, paraoxonase1 (PON1), predictive vascular disease in humans, include results prospective studies. The mechanisms by PON1 influences risk continue to be evaluated. It generally thought contributes antioxidant, and thus, antiatherogenic properties High Density Lipoproteins (HDL). Depleted antioxidant levels could factor for coronary artery disease. Hence, this study was done evaluate PON1, as CAD patients.This determine serum 50 controls 60 clinically ECG proven cases compare with total cholesterol triglycerides.Serum (p<0.001) were significantly lower than controls. Serum (p< 0.001) triglyceride higher negative correlation between PON 1 triglycerides. significant (p<0.05).From our present study, we can conclude exert protective effect on HDL preventing its oxidative damage. Further, decreased may CAD, likely explained derangement towards lipid peroxidation. This suggested an important provided protection stress peroxidation CAD. Thus, evaluating effects patients promising treatment prognosis

Language: Английский

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Paraoxonase 1: evolution of the enzyme and of its role in protecting against atherosclerosis

Current Opinion in Lipidology, Journal Year: 2024, Volume and Issue: 35(4), P. 171 - 178

Published: June 18, 2024

Purpose of review To the discoveries which led to concept that serum paraoxonase 1 (PON1) is inversely related atherosclerotic cardiovascular disease (ASCVD) incidence, how this association came be regarded as causal and such a role might have evolved. Recent findings Animal models suggest link between PON1 present on HDL atherosclerosis. Serum activity predicts ASCVD with similar reliability cholesterol, but at extremes high low there discordance being potentially more accurate. The gene family has its origins in earliest life forms. Its greatest hydrolytic towards lactones organophosphates, both can generated natural environment. It active wide range substrates thus conservation may resulted from improved survival species facing variety evolutionary challenges. Summary Protection against likely consequence some promiscuous PON1, nonetheless potential for exploitation improve risk prediction prevention ASCVD.

Language: Английский

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The effect of dual antioxidant modification on oxidative stress resistance and anti-dysfunction of non-split HDL and recombinant HDL

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 278, P. 134632 - 134632

Published: Aug. 9, 2024

Language: Английский

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High-Density Lipoproteins at the Interface between the NLRP3 Inflammasome and Myocardial Infarction

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1290 - 1290

Published: Jan. 20, 2024

Despite significant therapeutic advancements, morbidity and mortality following myocardial infarction (MI) remain unacceptably high. This clinical challenge is primarily attributed to two factors: delayed reperfusion the injury resulting from coronary reperfusion. Following reperfusion, there a rapid intracellular pH shift, disruption of ionic balance, heightened oxidative stress, increased activity proteolytic enzymes, initiation inflammatory responses, activation several cell death pathways, encompassing apoptosis, necroptosis, pyroptosis. The or pyroptosis encompasses multiprotein complex known as NLRP3 inflammasome. High-density lipoproteins (HDL) are endogenous particles whose components can either promote mitigate In this comprehensive review, we explore role inflammasome in context MI provide detailed analysis how HDL modulate process.

Language: Английский

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The importance of paraoxonase 1 activity in chronic kidney disease

Renal Failure, Journal Year: 2024, Volume and Issue: 46(2)

Published: July 10, 2024

Paraoxonase 1 (PON1) is one of the most significant antioxidative enzymes associated with high-density lipoprotein (HDL). It has been proved that involved in pathogenesis many diseases including chronic kidney disease (CKD). The association between PON1 and CKD seems to be mutual, such produces a decrease activity levels, while genetics may affect risk susceptibility CKD. Recent studies reveal serum observed non-dialyzed dialyzed patients as well renal transplant (RT) linked an increased vulnerability atherosclerosis. We intend summarize current literature concerning CKD, highlighting on main determinants activity, its oxidative stress, impact genetic polymorphism development, effect drugs nutritional state. Furthermore, evidence supporting implication reduced incident cardiovascular patients, also examined. appears despite lack standardization measurement, remains valuable biomarker for researchers through last decades, which contributes assessment antioxidant status having prognostic benefit adverse clinical outcomes at various stages etiologies disease.

Language: Английский

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Effects of dietary interventions and intermittent fasting on HDL function in obese individuals with T2DM: a randomized controlled trial

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 12, 2024

Language: Английский

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