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Search Results (199)

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Keywords = paraoxonase-1(PON-1)

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19 pages, 1637 KiB  
Article
High-Tyrosol/Hydroxytyrosol Extra Virgin Olive Oil Enhances Antioxidant Activity in Elderly Post-Myocardial Infarction Patients
by Mojgan Morvaridzadeh, Mehdi Alami, Nada Zoubdane, Hawa Sidibé, Hicham Berrougui, Tamàs Fülöp, Michel Nguyen and Abdelouahed Khalil
Antioxidants 2025, 14(7), 867; https://doi.org/10.3390/antiox14070867 - 16 Jul 2025
Viewed by 242
Abstract
Cardiovascular disease (CVD), particularly atherosclerotic cardiovascular disease (ASCVD), is the leading cause of death worldwide, driven by factors like oxidative stress, inflammation, and lipid metabolism disorders. Although phenolic compounds such as Tyrosol (Tyr) and Hydroxytyrosol (HTyr) found in extra virgin olive oil (EVOO) [...] Read more.
Cardiovascular disease (CVD), particularly atherosclerotic cardiovascular disease (ASCVD), is the leading cause of death worldwide, driven by factors like oxidative stress, inflammation, and lipid metabolism disorders. Although phenolic compounds such as Tyrosol (Tyr) and Hydroxytyrosol (HTyr) found in extra virgin olive oil (EVOO) have shown promising antioxidant and anti-inflammatory effects, their specific roles in modulating oxidative stress biomarkers and high-density lipoprotein (HDL) functionality in elderly populations, especially in those with prior myocardial infarction, are not fully understood. This study aimed to investigate the effects of EVOO phenolic compounds on oxidative stress biomarkers and HDL functionality, and related metabolic outcomes in both healthy and post-myocardial infarction (post-MI) elderly individuals. This pilot randomized clinical trial study included healthy and post-MI participants aged 65–85 years. Participants in each group were randomly assigned to consume 25 mL per day of one of three types of olive oils: high phenolic (HTyr/Tyr) extra virgin olive oil (HP-EVOO), extra virgin olive oil (EVOO), or refined olive oil (ROO) for a period of 26 weeks. Blood samples were collected at baseline and post-intervention to assess key biomarkers. Plasma levels of (poly)phenols, malondialdehyde (MDA), total antioxidant capacity (FRAP), lecithin-cholesterol acyltransferase activity (LCAT), and serum paraoxonase-1 (PON-1) activity were measured. A total of 34 individuals completed the study (mean age: 74 years). Baseline characteristics, including sex, age, body mass index (BMI), weight, blood pressure, and inflammatory markers like C-reactive protein (CRP) levels, did not differ significantly between the two groups. A significant increase in both FRAP levels and PON-1 activity was observed in post-MI participants following HP-EVOO consumption compared to baseline (p = 0.014). No significant changes were observed in MDA levels, LCAT activity, or plasma (poly)phenols. These results indicate that HP-EVOO may enhance antioxidant capacity, particularly FRAP and PON-1 activity, in elderly post-MI individuals. The observed differences between groups suggest that underlying cardiometabolic status may influence the response to olive oil phenolic compounds. Further studies are needed to explore the long-term cardiovascular effects. Full article
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19 pages, 1310 KiB  
Review
The Complexity of Oxidative Stress in Human Age-Related Diseases—A Review
by Alicja Płóciniczak, Ewelina Bukowska-Olech and Ewa Wysocka
Metabolites 2025, 15(7), 479; https://doi.org/10.3390/metabo15070479 - 15 Jul 2025
Viewed by 329
Abstract
The aging process is a complex and dynamic phenomenon influenced by genetic, environmental, and biochemical factors. One of the key contributors to aging and age-related diseases is oxidative stress, resulting from an imbalance between the generation of reactive oxygen species (ROS) and the [...] Read more.
The aging process is a complex and dynamic phenomenon influenced by genetic, environmental, and biochemical factors. One of the key contributors to aging and age-related diseases is oxidative stress, resulting from an imbalance between the generation of reactive oxygen species (ROS) and the efficiency of antioxidant defense systems. In this review, we introduce the concept of the oxidative stress complexity—a network encompassing ROS-generating systems, enzymatic and non-enzymatic antioxidants, and genetic determinants that collectively shape redox homeostasis. Emerging research highlights the significant influence of genetic variability on the activity and expression of selected and most examined antioxidant enzymes, including superoxide dismutase (SOD), paraoxonase 1 (PON1), catalase (CAT), and glutathione peroxidase (GPX), thereby modulating individual susceptibility to oxidative damage, disease onset, and the pace of aging. Particular attention is paid to the interplay among oxidative stress, chronic inflammation, and metabolic dysfunction in the pathogenesis of various age-related disorders. By integrating findings from molecular studies, clinical research, and population genetics, we discuss the diagnostic and prognostic potential of antioxidant enzymes as biomarkers of aging and explore strategies for redox-modulating interventions. Understanding these interrelations is essential for identifying biomarkers of biological aging and developing personalized strategies aimed at promoting healthy aging and reducing the risk of chronic disease. Full article
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24 pages, 7057 KiB  
Article
Synergistic Effect of Banaba Leaf Extract and Policosanol (Raydel®) Ameliorate High Cholesterol and High Galactose-Diet Induced Adverse Events in Zebrafish
by Kyung-Hyun Cho, Sang Hyuk Lee, Yunki Lee, Ashutosh Bahuguna, Ji-Eun Kim, Krismala Djayanti and Cheolmin Jeon
Pharmaceuticals 2025, 18(6), 860; https://doi.org/10.3390/ph18060860 - 9 Jun 2025
Viewed by 974
Abstract
Background: This study aimed to explore the therapeutic potential of a dietary regimen of banaba leaf extract (BNB), policosanol (PCO, Raydel®), and their combination (BNB+PCO), to mitigate high cholesterol (HC) and high galactose (HG) diet-induced dyslipidemia, hyperglycemia, oxidative stress, senescence, [...] Read more.
Background: This study aimed to explore the therapeutic potential of a dietary regimen of banaba leaf extract (BNB), policosanol (PCO, Raydel®), and their combination (BNB+PCO), to mitigate high cholesterol (HC) and high galactose (HG) diet-induced dyslipidemia, hyperglycemia, oxidative stress, senescence, and organ damage in zebrafish (Danio rerio). Methodology: Zebrafish (n = 28/group) were fed with HC (4% w/w)+HG (30% w/w) or HC+HG supplemented either with BNB (0.1% w/w) or PCO (0.1% w/w) or BNB+PCO (0.1% w/w each). Following 6 weeks of dietary intervention, biochemical and histopathological examinations across the groups were performed. Results: Post 6 weeks of consumption, the BNB+PCO group exhibited a significant 40% decrease in body weight (BW) relative to the BW of the HC+HG group, while the BNB or PCO groups displayed nonsignificant changes in BW. Both BNB and PCO reduced HC+HG-induced dyslipidemia and hyperglycemia; however, co-administration (BNB+PCO) demonstrated a significantly greater therapeutic effect in countering these conditions compared to either BNB or PCO alone. A similar effect of the BNB+PCO combination was observed on the elevation of plasma sulfhydryl content, paraoxonase (PON), and ferric ion reduction activity (FRA), with notably ~1.2-times (p < 0.01) higher levels compared to their corresponding values observed in the BNB or PCO groups. Significantly diminished plasma AST, ALT, hepatic interleukin 6 (IL-6) levels, and fatty liver changes were observed in response to BNB+PCO, compared to either BNB or PCO alone. Also, BNB+PCO displayed a higher curative effect against HC+HG-induced impairment of tissue regeneration than BNB or PCO alone. A notable effect of BNB+PCO was perceived in protecting kidneys, testis, and ovary damage. Consistently, BNB+PCO showed a profound impact on mitigating HC+HG elevated reactive oxygen species (ROS) generation, apoptosis, cellular senescence, and accumulation of brain-binding lipid proteins (BLBPs) and 4-hydroxynoneal (4-HNE) in the brain. Conclusions: The findings highlight the synergistic effects of the BNB and PCO combination to mitigate the adversity posed by the consumption of the HC+HG diet. Full article
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16 pages, 2112 KiB  
Article
Beyond Individual Acute Phase Protein Assessments: Introducing the Acute Phase Index (API) as a Prognostic Indicator in Dogs with Malignant Neoplasia
by Martina Baldin, Maria Elena Gelain, Giacomo Marolato, Silvia Bedin, Michele Berlanda, Manuela Zanetti, Filippo Torrigiani, Alessia Giordano, Pierangelo Moretti, Donatella Scavone and Federico Bonsembiante
Vet. Sci. 2025, 12(6), 533; https://doi.org/10.3390/vetsci12060533 - 1 Jun 2025
Viewed by 1013
Abstract
Acute phase proteins (APPs) are part of the innate immune response, changing during inflammation. An Acute Phase Index (API) is a calculated value that combines multiple APPs. In human medicine, the introduction of APIs has improved outcome monitoring. In veterinary medicine, APIs have [...] Read more.
Acute phase proteins (APPs) are part of the innate immune response, changing during inflammation. An Acute Phase Index (API) is a calculated value that combines multiple APPs. In human medicine, the introduction of APIs has improved outcome monitoring. In veterinary medicine, APIs have been evaluated in livestock and dogs with Leishmaniasis. This study aimed to calculate an API and evaluate its significance in cancer-bearing dogs. Sera were collected from 55 dogs, which were classified by neoplastic category and survival times (> or < than 30 and 90 days). For 32 dogs, multiple samples were available. The API included C-Reactive Protein (CRP) and haptoglobin as positive APPs, and albumin and Paraoxonase-1 (PON-1) as negative APPs. An alternative API excluding PON-1 was calculated. PON-1 levels were lower in round-cell tumors, suggesting increased oxidative stress. Moreover, API increased and PON-1 activity decreased in the last sample in dogs that died before the end of the study. Dogs with shorter survival times showed increased APIs and CRP levels. APIs with and without PON-1 greater than 0.049 and 0.202 at the first sampling were associated with a 3.7- and 4.4-fold higher probability of death, respectively. These results suggest a potential prognostic value of API in dogs with neoplasia. Full article
(This article belongs to the Section Veterinary Internal Medicine)
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12 pages, 232 KiB  
Article
Tetranectin and Paraoxonase 1 in Patients with Varying Stages of Heart Failure: A Cross-Sectional Analysis
by Paula Alexandra Vulciu, Luminita Pilat, Maria-Daniela Mot, Voicu Dascau, Calin Daniel Popa, Norberth-Istvan Varga and Maria Puschita
Clin. Pract. 2025, 15(5), 86; https://doi.org/10.3390/clinpract15050086 - 25 Apr 2025
Viewed by 450
Abstract
Background: Heart failure (HF) is a leading cause of mortality across the globe, prompting ongoing research into novel biomarkers for improved risk stratification and patient management. Methods: This cross-sectional study aimed to investigate the relationship between two promising biomarkers, tetranectin and paraoxonase 1, [...] Read more.
Background: Heart failure (HF) is a leading cause of mortality across the globe, prompting ongoing research into novel biomarkers for improved risk stratification and patient management. Methods: This cross-sectional study aimed to investigate the relationship between two promising biomarkers, tetranectin and paraoxonase 1, and the severity of heart failure in a cohort of 87 patients with cardiovascular risk factors. Participants were categorized into three groups based on their New York Heart Association (NYHA) classification: no HF (Control), NYHA class I (G1), and NYHA class II-IV (G2). Results: Our analysis revealed a stepwise decrease in both TETRA and PON1 levels with increasing HF severity, with the Control group exhibiting the highest levels and the G2 group the lowest. Interestingly, a significant positive correlation between TETRA and PON1 was observed only in the Control group, suggesting a potential interplay between these biomarkers in healthy individuals that may be disrupted with the onset of HF. Furthermore, both TETRA and PON1 were positively associated with left ventricular ejection fraction (LVEF) and negatively associated with diastolic dysfunction, indicating their potential involvement in both systolic and diastolic cardiac function. Conclusions: These findings suggest that TETRA and PON1 may serve as valuable biomarkers for assessing HF severity and prognosis. Further research is warranted to validate these findings in larger, prospective studies and to explore their clinical utility in guiding treatment decisions. Full article
25 pages, 2512 KiB  
Review
How Does HDL Participate in Atherogenesis? Antioxidant Activity Versus Role in Reverse Cholesterol Transport
by Paul N. Durrington, Bilal Bashir and Handrean Soran
Antioxidants 2025, 14(4), 430; https://doi.org/10.3390/antiox14040430 - 2 Apr 2025
Cited by 1 | Viewed by 1464
Abstract
Low-density lipoprotein (LDL) chemically modified by reactive oxygen species (ROS), for example, leaking from red blood cells in the vascular compartment, more readily crosses the vascular endothelium than does nonoxidatively modified LDL to enter tissue fluid. Oxidatively modified LDL (oxLDL) may also be [...] Read more.
Low-density lipoprotein (LDL) chemically modified by reactive oxygen species (ROS), for example, leaking from red blood cells in the vascular compartment, more readily crosses the vascular endothelium than does nonoxidatively modified LDL to enter tissue fluid. Oxidatively modified LDL (oxLDL) may also be created in the tissue fluid by ROS leaking from cells by design, for example, by inflammatory white cells, or simply leaking from other cells as a consequence of oxygen metabolism. As well as oxLDL, glycatively modified LDL (glycLDL) is formed in the circulation. High-density lipoprotein (HDL) appears capable of decreasing the burden of lipid peroxides formed on LDL exposed to ROS or to glucose and its metabolites. The mechanism for this that has received the most attention is the antioxidant activity of HDL, which is due in large part to the presence of paraoxonase 1 (PON1). PON1 is intimately associated with its apolipoprotein A1 component and with HDL’s lipid domains into which lipid peroxides from LDL or cell membranes can be transferred. It is frequently overlooked that for PON1 to hydrolyze lipid substrates, it is essential that it remain by virtue of its hydrophobic amino acid sequences within a lipid micellar environment, for example, during its isolation from serum or genetically modified cells in tissue culture. Otherwise, it may retain its capacity to hydrolyze water-soluble substrates, such as phenyl acetate, whilst failing to hydrolyze more lipid-soluble molecules. OxLDL and probably glycLDL, once they have crossed the arterial endothelium by receptor-mediated transcytosis, are rapidly taken up by monocytes in a process that also involves scavenger receptors, leading to subendothelial foam cell formation. These are the precursors of atheroma, inducing more monocytes to cross the endothelium into the lesion and the proliferation and migration of myocytes present in the arterial wall into the developing lesion, where they transform into foam cells and fibroblasts. The atheroma progresses to have a central extracellular lake of cholesteryl ester following necrosis and apoptosis of foam cells with an overlying fibrous cap whilst continuing to grow concentrically around the arterial wall by a process involving oxLDL and glycLDL. Within the arterial wall, additional oxLDL is generated by ROS secreted by inflammatory cells and leakage from cells generally when couplet oxygen is reduced. PON1 is important for the mechanism by which HDL opposes atherogenesis, which may provide a better avenue of inquiry in the identification of vulnerable individuals and the provision of new therapies than have emerged from the emphasis placed on its role in RCT. Full article
(This article belongs to the Special Issue Antioxidant Role of High-Density Lipoprotein)
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26 pages, 5024 KiB  
Article
Synergistic Efficacy of Policosanol (Raydel®) and Banaba Leaf Extract to Treat Hyperglycemia and Dyslipidemia in Streptozotocin-Induced Diabetic and Hyperlipidemic Zebrafish (Danio rerio): Protection of Liver and Kidney with Enhanced Tissue Regeneration
by Kyung-Hyun Cho, Sang Hyuk Lee, Yunki Lee, Ashutosh Bahuguna and Ji-Eun Kim
Pharmaceuticals 2025, 18(3), 362; https://doi.org/10.3390/ph18030362 - 3 Mar 2025
Cited by 1 | Viewed by 2187
Abstract
Background: The efficacy of banaba leaf extract was tested against carboxymethyllysine (CML)-induced toxicity in embryos and adult zebrafish. Additionally, the individual and combined effects of banaba (BNB) and policosanol (PCO) were analyzed to alleviate dyslipidemia, hyperglycemia, and associated effects in streptozotocin (STZ)-induced hyperlipidemic [...] Read more.
Background: The efficacy of banaba leaf extract was tested against carboxymethyllysine (CML)-induced toxicity in embryos and adult zebrafish. Additionally, the individual and combined effects of banaba (BNB) and policosanol (PCO) were analyzed to alleviate dyslipidemia, hyperglycemia, and associated effects in streptozotocin (STZ)-induced hyperlipidemic diabetic zebrafish. Methodology: The high cholesterol diet (HCD, final 4%, w/w)-fed zebrafish were injected with STZ to develop diabetes and were subsequently fed with either HCD or HCD+BNB (final 0.1% w/w) or HCD+PCO (final 0.1% w/w) or HCD+BNB+PCO (each final 0.1%, w/w) each for 14 days. The zebrafish tail fin was amputated to assess tissue regeneration, while the organs and blood were collected for histological and biochemical analysis. Results: Severely compromised embryo survivability and developmental defects were noticed in the CML-injected group that significantly improved following BNB exposure. Similarly, CML-induced acute paralysis and mortality of adult zebrafish were effectively mitigated by the treatment with BNB. In the hyperlipidemic diabetic zebrafish, both BNB and PCO supplementation displayed the hypoglycemic effect; however, a remarkable reduction (p < 0.05) in blood glucose levels was observed in the BNB+PCO group, around 14% and 16% less than the BNB group and PCO group, respectively. Likewise, higher tail fin regeneration was noticed in response to BNB+PCO supplementation. Both BNB and PCO have a substantial counter-effect against HCD+STZ-induced dyslipidemia. However, the combined supplementation (BNB+PCO) displayed a significantly better effect than that of BNB and PCO alone to alleviate total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C). The most impressive impact of BNB+PCO was noticed in the elevation of high-density lipoprotein cholesterol (HDL-C), which was ~1.5 times higher than the HDL-C level in response to BNB and PCO. Also, BNB+PCO effectively reduced the malondialdehyde (MDA) and elevated the plasma sulfhydryl content, paraoxonase (PON), and ferric ion reduction (FRA) activity. Histological analyses revealed a significant effect of BNB+PCO in preventing inflammatory infiltration, fatty liver changes, and interleukin-6 production. Similarly, a notably better effect of BNB+PCO compared to their individual effect was noticed in preventing kidney damage and mitigation of ROS generation, apoptosis, and cellular senescence. Conclusions: The finding establishes the substantial effect of BNB and PCO in countering hyperglycemia, dyslipidemia, and associated disorders, which synergistically improved following the combined supplementation with BNB+PCO. Full article
(This article belongs to the Special Issue Natural Products in Diabetes Mellitus: 2nd Edition)
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15 pages, 4196 KiB  
Article
Aerobic-Resistance Training with Royal Jelly Supplementation Has a Synergistic Effect on Paraoxonase 1 Changes and Liver Function in Women with MASLD
by Roya Askari, Nazanin Rabani, Hamid Marefati, Marzie Sadat Azarnive, Matteo Pusceddu and Gian Mario Migliaccio
Medicina 2025, 61(2), 349; https://doi.org/10.3390/medicina61020349 - 17 Feb 2025
Viewed by 1418
Abstract
Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a clinical pathological syndrome characterized by steatosis and fat accumulation in liver parenchymal cells in patients without a history of excessive alcohol drinking. Currently, there is no definitive treatment for MASLD, and [...] Read more.
Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a clinical pathological syndrome characterized by steatosis and fat accumulation in liver parenchymal cells in patients without a history of excessive alcohol drinking. Currently, there is no definitive treatment for MASLD, and its prevalence increases with age and obesity, and after menopause. Among the ways to treat it, we can mention regular sports exercises and the use of natural supplements. Therefore, the aim of this research is to investigate and compare the effects of aerobic-resistance training with royal jelly supplementation on changes in paraoxonase 1, oxidized LDL, liver function, and lipid profile in postmenopausal women with Dysfunction-Associated Steatotic Liver Disease. Materials and Methods: This semi-experimental study involved 23 women with Dysfunction-Associated Steatotic Liver Disease with an average weight (71.34 ± 11.63 kg), age (48.54 ± 3.88 years), and body mass index (27.63 ± 4.20 kg/m2). They were randomly divided into two groups: exercise + supplement (n = 12) and exercise + placebo (n = 11). Both groups performed eight-station resistance exercises (8–12 repetitions in 2–4 sets) for 8 weeks, with three sessions per week (for 35–40 min, from 10-15 RPE), and then, for 10–15 min of active rest, they performed aerobic exercises with an intensity of 40–85% of the target heart rate, in two-minute intervals with 45 s of active rest. Royal jelly supplement (500 mg on training days, before each training session) was consumed. Blood sampling was done before and 48 h after the last training session. Statistical analysis was performed using a variance test with repeated measures (two groups × two stages of pre-test-post-test) in SPSS software (Version 26) with a significance level of p < 0.05. Results: The results of the statistical analysis show that the effects of eight weeks of exercise + supplement and exercise + placebo on PON1, oxLDL, lipid profiles (HDL, LDL, TC, and TG), and liver enzymes (ALT, AST) in women with non-alcoholic fatty liver showed a significant difference (p < 0.05). The results show a significant increase in PON1 (p = 0.008) and HDL (p = 0.005) in the exercise + supplement group compared to the exercise + placebo group. But significant decreases in oxLDL (p = 0.031), TC (p = 0.045), TG (p = 0.013), LDL (p = 0.027), ALT (p = 0.015) and AST (p = 0.009) were observed in the exercise + supplement group compared to the exercise + placebo group (<0.05). The results show a significant increase in PON1 (p = 0.008) and HDL (p = 0.005) in the exercise + supplement group compared to the exercise + placebo group. However, significant decreases in oxLDL (p = 0.031), TC (p = 0.045), TG (p = 0.013), LDL (p = 0.027), ALT (p = 0.015), and AST (p = 0.009) was observed in the exercise + supplement group compared to the exercise + placebo group. Conclusions: Based on the results, it can be concluded that aerobic-resistance exercises with the addition of royal jelly can probably be an efficient and recommended strategy to minimize the harmful effects of Dysfunction-Associated Steatotic Liver Disease by affecting the activity of liver enzymes, paraoxonase 1, LDL oxidation, and lipid profile. Although exercise alone also yielded favorable results, according to the findings of this research, it can be said that exercise, combined with the use of royal jelly supplements, may have more positive effects on reducing liver complications and improving body function. However, in order to obtain more accurate scientific evidence, it is necessary to investigate more doses and timing of royal jelly in future studies. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Treatment of Chronic Liver Disease)
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22 pages, 2223 KiB  
Article
PON-1 and PON-2 Polymorphisms and PON-1 Paraoxonase Activity in People Living with HIV-1
by Cadiele Oliana Reichert, Débora Levy, Luciana Morganti Ferreira Maselli, Joel da Cunha, Sandra Fátima Menosi Gualandro and Sérgio Paulo Bydlowski
Antioxidants 2025, 14(2), 209; https://doi.org/10.3390/antiox14020209 - 12 Feb 2025
Cited by 1 | Viewed by 908
Abstract
Antiretroviral therapy (ART) has significantly improved the life expectancy of people living with HIV-1 (PLWH). However, prolonged ART use is linked to metabolic alterations and oxidative stress. The paraoxonase (PON) enzymes, especially PON-1 and PON-2, are critical in maintaining antioxidant balance. Their activity [...] Read more.
Antiretroviral therapy (ART) has significantly improved the life expectancy of people living with HIV-1 (PLWH). However, prolonged ART use is linked to metabolic alterations and oxidative stress. The paraoxonase (PON) enzymes, especially PON-1 and PON-2, are critical in maintaining antioxidant balance. Their activity can be influenced by polymorphisms such as Q192R and L55M in PON-1 and A148G and S311C in PON-2. This study examines the impact of these polymorphisms on paraoxonase activity, lipid metabolism, and infection markers in PLWH under various ART regimens. This is a case-control study with 525 participants, 175 healthy controls (HC) and 350 PLWH divided into subgroups: T0 (ART-naïve, n = 48), T1 (ART with reverse transcriptase inhibitors, n = 159), and T2 (ART with protease inhibitors, n = 143). Paraoxonase activity was higher in PLWH (123.0; IQR: 62.0–168.0) compared to HC (91.0; IQR: 48.0–136.0, p < 0.001) but similar between HC and T0 (p = 0.594). T1 (125.0; IQR: 65.5–166.0) and T2 (123.0; IQR: 61.0–182.0) showed higher activity than HC (p = 0.002 and 0.003). Among 61 complete genotypes, 13 were unique to PLWH and 6 to HC (p < 0.001). L55L was more frequent in HC (49.7% vs. 36.9% in PLWH), while M55M was higher in PLWH (p = 0.004). The S311C genotype was more frequent in HC (39.2%) than PLWH (24.9%) (p = 0.003). The L55L genotype conferred 59.9% protection against HIV-1 (OR: 0.401; 95% CI: 0.228–0.704), while the M allele increased susceptibility by ~69% (OR: 1.694; 95% CI: 1.173–2.446). The M55M genotype and/or M allele may be linked to HIV-1 susceptibility. Prolonged ART use elevates PON-1 activity in PLWH. Full article
(This article belongs to the Special Issue Antioxidant Role of High-Density Lipoprotein)
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24 pages, 13252 KiB  
Article
A Comparative Effect of 12-Week Dietary Intervention of Policosanol (Raydel®) and Red Yeast Rice (RYR, Kobayashi) in Managing Dyslipidemia and Organ Damage in Hyperlipidemic Zebrafish
by Kyung-Hyun Cho, Ashutosh Bahuguna, Ji-Eun Kim, Sang Hyuk Lee, Yunki Lee and Cheolmin Jeon
Pharmaceuticals 2025, 18(2), 200; https://doi.org/10.3390/ph18020200 - 1 Feb 2025
Cited by 1 | Viewed by 2045
Abstract
Background: A comparative 12-week dietary intervention of red yeast rice (RYR, Beni-koji, Kobayashi, Japan) and Cuban policosanol (PCO, Raydel®, Thornleigh, Australia) was assessed for dyslipidemia, antioxidant status, and vital organ functionality in hyperlipidemic zebrafish. Methods: Hyperlipidemic zebrafish were supplemented with [...] Read more.
Background: A comparative 12-week dietary intervention of red yeast rice (RYR, Beni-koji, Kobayashi, Japan) and Cuban policosanol (PCO, Raydel®, Thornleigh, Australia) was assessed for dyslipidemia, antioxidant status, and vital organ functionality in hyperlipidemic zebrafish. Methods: Hyperlipidemic zebrafish were supplemented with a high-cholesterol diet (HC, final 4%, w/w) infused with either a powdered RYR tablet (final 1.0%, w/w), a PCO tablet (final 1.0%, w/w), or a combination of 0.5% (w/w) each of RYR and PCO powder for 12 weeks. Subsequently, blood and organs were collected and processed for biochemical and histological examination. Results: RYR and PCO consumption showed a substantial effect against HC-induced hyperlipidemia by reducing the total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C). Exclusively, PCO supplementation revealed a significant elevation in the HC-diminished high-density lipoprotein cholesterol (HDL-C). In addition, PCO supplementation showed a significant elevation in plasma ferric ion-reducing ability (FRA) and sulfhydryl content, as well as alleviating the blood glucose level of hyperlipidemic zebrafish. The most noteworthy impact, with a significant two-fold (p < 0.001) augmentation of HC-diminished plasma paraoxonase (PON) activity, was observed in response to PCO. In contrast, the RYR supplementation failed to establish curative effects against HC-disturbed plasma antioxidant variables and blood glucose levels. The histological outcome revealed a severe toxicological impact of the RYR on the liver, reflected by fatty liver changes and three-fold heightened IL-6 production compared to HC control. Contrastingly, PCO exhibited significant hepatoprotection and effectively neutralized the hepatic toxicity triggered by HC and RYR. Also, RYR showed kidney atrophy, intense ROS generation, apoptosis, and senescence. Conversely, the PCO supplementation protected the kidney from HC- and RYR-induced toxicity. Likewise, PCO supplementation notably alleviated histological alterations and oxidative stress in the brain, ovary, and testis of hyperlipidemic zebrafish. Conclusions: This comparative study establishes PCO’s therapeutic effect against the challenges posed by HC, while RYR emerged with serious toxicological concerns towards the liver, kidney, and other organs of hyperlipidemic zebrafish. Full article
(This article belongs to the Section Pharmacology)
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13 pages, 1431 KiB  
Article
The Role of Paraoxonase-1 Activity, Apolipoprotein B Levels, and Apolipoprotein B/Apolipoprotein A-I Ratio as Risk Markers for Aortic Stenosis in Patients with a Bicuspid Aortic Valve
by Maria Kwiatkowska, Agnieszka Mickiewicz, Aleksandra Krzesińska, Agnieszka Kuchta, Maciej Jankowski, Marcin Gruchała and Marcin Fijałkowski
Antioxidants 2025, 14(2), 167; https://doi.org/10.3390/antiox14020167 - 30 Jan 2025
Viewed by 817
Abstract
The bicuspid aortic valve (BAV) is commonly associated with the early degeneration of the aortic valve. Up to 45% of BAV patients over the age of 50 develop aortic stenosis (AS). Although published data indicate a robust interplay between lipids and calcific AS [...] Read more.
The bicuspid aortic valve (BAV) is commonly associated with the early degeneration of the aortic valve. Up to 45% of BAV patients over the age of 50 develop aortic stenosis (AS). Although published data indicate a robust interplay between lipids and calcific AS in tricuspid aortic valve patients, the studies on the BAV population are lacking. We aimed to evaluate the association between selected lipid markers and the occurrence of AS in BAV patients. Methods: The study included 76 adults (21 female) with a BAV diagnosed by echocardiography, divided by age and AS diagnosis. Biochemical parameters concentrations in serum were measured: high density lipoprotein cholesterol (HDL-C) levels by standard enzymatic colorimetric tests, low density lipoprotein cholesterol (LDL-C) levels by the Friedewald formula, apolipoprotein A-I (Apo AI) and apolipoprotein B (Apo B) serum concentration by the nephelometric method, and paraoxonase-1 activity (PON-1 ASE) and arylesterase activity (PON-1 ARE) based on paraoxon and phenyl acetate hydrolysis. Results: A total of 54 patients (15 female) were more than 45 years old and 22 (6 female) were 45 or less years old. BAV patients with AS aged ≤45 had higher levels of Apo B, compared to those without AS [110.5 (102–132) vs. 95.6 (77–101) mg/d; p 0.044]. Similarly, Apo B/Apo AI ratio was higher in BAV patients with AS aged ≤45, compared to those without AS [(0.8 (0.7–1) vs. 0.6 (0.5–0.7); p 0.029]. In the group aged ≤45, Apo B showed a positive correlation with the aortic valve peak transvalvular velocity (AV Vmax) measurement (R Spearman 0.6, p 0.004). We found also that, among young BAV patients, those with AS had a lower level of PON-1 ARE compared to the cohort without AS [63.4 (52–80) vs. 85.3 (70–102); p 0.012]. We did not find any differences in lipid parameters in patients aged >45. Conclusions The metabolic link between Apo B level and Apo B/AI ratio with AS presence in BAV patients under 45 years of age suggests a significant impact of these parameters on the earlier development of AS in the BAV population. Molecules associated with high density lipoprotein and its antioxidant function, such as PON1, are valuable markers for AS development, compared to HDL-C and LDL-C levels. Full article
(This article belongs to the Special Issue Antioxidant Role of High-Density Lipoprotein)
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15 pages, 586 KiB  
Article
Excessive Weight Gain During Pregnancy Increased Ponoxarase 1 Level in Neonatal Cord Blood
by Serhat Ege, Hasan Akduman, Ayşegül Aşır and Tuğcan Korak
Antioxidants 2025, 14(1), 105; https://doi.org/10.3390/antiox14010105 - 17 Jan 2025
Cited by 1 | Viewed by 1057
Abstract
Maternal obesity is increasingly recognized as a risk factor for adverse fetal outcomes, primarily through its association with heightened oxidative stress. This study aimed to evaluate oxidative stress markers in umbilical cord blood of neonates born to obese mothers. Sixty-three pregnant women, who [...] Read more.
Maternal obesity is increasingly recognized as a risk factor for adverse fetal outcomes, primarily through its association with heightened oxidative stress. This study aimed to evaluate oxidative stress markers in umbilical cord blood of neonates born to obese mothers. Sixty-three pregnant women, who were of normal weight at the start of pregnancy but classified as obese at term, were included. Umbilical cord blood samples were collected immediately post-delivery and analyzed for serum oxidative stress markers (total oxidant status (TOS), total antioxidant status (TAS), paraoxanase (PON), aryl esterase, thiol, and catalase activities). Protein interaction networks were generated using Cytoscape (v3.10.3), and the overlapping proteins were further analyzed for functional annotations with ShinyGO (0.80). The top ten significantly enriched pathways were identified with a false discovery rate (FDR) threshold of <0.05. Significant associations were found between maternal BMI change and paraoxonase 1 (PON1) levels in umbilical cord blood, while no correlation was observed with other oxidative (total oxidant status) and antioxidant markers (total antioxidant status, aryl esterase, thiol, and catalase). Additionally, the correlation analysis showed a significant relationship between BMI change and fetal gestational age, but not with other demographic or clinical features. A total of 24 common protein interactors associated with PON1, obesity, and oxidative stress were identified. Functional annotation analysis revealed significant enrichment in antioxidant and oxidoreductase activities, along with pathways involved in insulin resistance, AGE-RAGE signaling, and atherosclerosis. Maternal obesity may specifically affect PON1 activity, potentially serving as a compensatory response to oxidative stress in neonates, suggesting PON1 as a possible biomarker for oxidative stress-related metabolic disturbances in neonates of obese mothers, with implications for monitoring and managing pregnancy outcomes in obese populations. Full article
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24 pages, 11998 KiB  
Article
The Consumption of Beeswax Alcohol (BWA, Raydel®) Improved Zebrafish Motion and Swimming Endurance by Protecting the Brain and Liver from Oxidative Stress Induced by 24 Weeks of Supplementation with High-Cholesterol and D-Galactose Diets: A Comparative Analysis Between BWA and Coenzyme Q10
by Kyung-Hyun Cho, Yunki Lee, Ashutosh Bahuguna, Sang Hyuk Lee, Chae-Eun Yang, Ji-Eun Kim and Hyo-Shin Kwon
Antioxidants 2024, 13(12), 1488; https://doi.org/10.3390/antiox13121488 - 5 Dec 2024
Cited by 2 | Viewed by 2048
Abstract
The prolonged consumption of D-galactose (Gal) has been associated with severe damage in the liver and brain via exacerbation of oxidative stress, non-enzymatic glycation, and the aging process. The current study was initiated for a comparative assessment of beeswax alcohol (BWA, final 0.5% [...] Read more.
The prolonged consumption of D-galactose (Gal) has been associated with severe damage in the liver and brain via exacerbation of oxidative stress, non-enzymatic glycation, and the aging process. The current study was initiated for a comparative assessment of beeswax alcohol (BWA, final 0.5% and 1.0% w/w) and coenzyme Q10 (CoQ10, final 0.5% and 1.0% w/w) against high-cholesterol (HC, final 4%, w/w) and -galactose (Gal, final 30%, w/w)-induced adverse events in zebrafish during 24 weeks of consumption. The survivability of zebrafish decreased to 82.1% due to HC+Gal exposure, but this was substantially improved (91.0%) with the consumption of 0.5% and 1.0% BWA. In contrast, no protective effect of CoQ10 consumption (1.0%) was observed on the survivability of zebrafish. Nevertheless, both BWA and CoQ10 displayed a significant (p < 0.001) preventive effect against HC+Gal-induced body weight enhancement. The HC+Gal-induced cognitive changes, marked by staggered and confused swimming behavior, and retarded swimming speed and motion patterns (restricted to the bottom of the tank), were efficiently restored by BWA. A significantly higher residence time in the upper half of the tank, 3.1-and 4.5-fold reduced latency time along with 3.5-fold and 4.1-fold higher swimming distance, was logged in the 0.5% and 1.0% BWA groups, respectively, than the zebrafish that consumed HC+Gal. In addition, BWA effectively enhanced plasma ferric ion reduction (FRA) and paraoxonase (PON) activity and alleviated the total cholesterol (TC), triglyceride (TG), and blood glucose levels disrupted by the consumption of HC+Gal. Also, the HC+Gal-alleviated plasma high-density lipoprotein-cholesterol (HDL-C) was 2.6-fold (p < 0.001) enhanced in the group that consumed 1.0% BWA, which was significantly 1.5-fold (p < 0.001) better than the effect of 1.0% CoQ10. Similarly, BWA displayed a superior impact over CoQ10 to mitigate HC+Gal-induced plasma AST and ALT levels, hepatic IL-6 production, generation of oxidized species, cellular senescence, and fatty liver changes. Moreover, BWA protects the brain against HC+Gal-induced oxidative stress, apoptosis, and myelin sheath degeneration. Conclusively, compared to CoQ10, BWA efficiently can the HC+Gal-impaired brain and liver functionality to subside and improves the dyslipidemia and cognitive behavior of zebrafish. Full article
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12 pages, 1228 KiB  
Article
Citrus bergamia Extract, a Natural Approach for Cholesterol and Lipid Metabolism Management: A Randomized, Double-Blind Placebo-Controlled Clinical Trial
by Amelia Spina, Fabio Amone, Vincenzo Zaccaria, Violetta Insolia, Anna Perri, Danilo Lofaro, Francesco Puoci and Vincenzo Nobile
Foods 2024, 13(23), 3883; https://doi.org/10.3390/foods13233883 - 30 Nov 2024
Viewed by 4663
Abstract
Strategies for controlling cholesterol and lipid metabolism, including the use of food supplements, are part of the non-pharmacological intervention to ameliorate cardiovascular health. To demonstrate the efficacy of a standardized flavonoids (150 mg/day) extract from Citrus bergamia on cholesterol and lipid management, a [...] Read more.
Strategies for controlling cholesterol and lipid metabolism, including the use of food supplements, are part of the non-pharmacological intervention to ameliorate cardiovascular health. To demonstrate the efficacy of a standardized flavonoids (150 mg/day) extract from Citrus bergamia on cholesterol and lipid management, a placebo-controlled clinical trial on 64 subjects with high cholesterol was carried out. The total study duration was 4 months, with intermediate checkpoints at 1-month intervals. Low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) cholesterol, total cholesterol (TC) levels, oxidized low-density lipoprotein (ox-LDL), and paraoxonase activity (PON1) were measured as primary endpoints (efficacy evaluation), while weight, blood pressure, hepatic and renal function blood markers were measured as secondary endpoints (safety evaluation). After 4 months, both TC and LDL-C significantly decreased by 8.8% and 11.5%, respectively, along with a 5.5% increase in HDL-C which was trending towards significance. In addition, ox-LDL was significantly reduced by 2.0%, while PON1 was significantly increased by 6.5%. The secondary endpoints were not changed during the study, demonstrating a good tolerability of the test product. Our findings demonstrate the efficacy of the extract as a natural approach for cholesterol and lipid metabolism management. Full article
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
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13 pages, 712 KiB  
Article
Oxidative Status and Lipid Metabolism Analytes in Dogs with Mast Cell Tumors: A Preliminary Study
by Argyrios Ginoudis, Dimitra Pardali, Mathios E. Mylonakis, Androniki Tamvakis, Asta Tvarijonaviciute, Evgenia Lymperaki, Jose Joaquin Ceron and Zoe Polizopoulou
Antioxidants 2024, 13(12), 1473; https://doi.org/10.3390/antiox13121473 - 29 Nov 2024
Viewed by 1495
Abstract
Mast cell tumors (MCTs) are common skin neoplasms in dogs. Prognostic indicators include histologic grade, clinical stage, high Ki-67 index, elevated argyrophilic nucleolus organizer regions (AgNOR) index, c-kit mutations, and recurrence after surgery. Blood serum redox status has been shown to correlate with [...] Read more.
Mast cell tumors (MCTs) are common skin neoplasms in dogs. Prognostic indicators include histologic grade, clinical stage, high Ki-67 index, elevated argyrophilic nucleolus organizer regions (AgNOR) index, c-kit mutations, and recurrence after surgery. Blood serum redox status has been shown to correlate with prognostic factors in canine lymphoma and mammary tumors. This study aimed to assess the correlation between established prognostic factors and serum redox status and lipid metabolism analytes in dogs with MCTs. Dogs with cutaneous (n = 33) or subcutaneous (n = 6) MCTs, without comorbidities, were studied. Staging was evaluated based on cytology of regional lymph nodes and ultrasound-guided liver and spleen aspiration cytology. Histologic grading and immunohistochemical staining for Ki-67 and KIT patterns were performed on excised tumor specimens. Dogs were categorized by Patnaik grading (1–3), Kiupel grading (low/high), metastatic status, Ki-67 positive nuclei per cm2 (>23 or ≤23), and KIT pattern (I, II–III). Paraoxonase-1, Butyrylcholinesterase, Cupric Reducing Antioxidant Capacity (CUPRAC), Diacron Reactive Oxygen Metabolites (d-ROMs), and oxy-adsorbent levels were measured before any therapeutic intervention. ANOVA and independent t-tests were used to detect differences in the mean values among groups. Paraoxonase-1 activity was significantly lower in Patnaik grade 3 (p = 0.003) and Kiupel high-grade (p = 0.022) MCTs. No significant differences were found in CUPRAC, d-ROMs, or oxy-adsorbent levels across different prognostic groups. This study found a significant correlation between histologic grading and Paraoxonase-1 activity, suggesting a potential role of Paraoxonase-1 as a prognostic biomarker in canine MCTs. Full article
(This article belongs to the Special Issue Antioxidant Role of High-Density Lipoprotein)
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