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Research on ozonated sunflower oil (OSO) is mostly restricted to its topical application, whereas the functional and toxicological assessment of oral OSO consumption is yet to be solved. Herein, OSO was orally supplemented in rats to assess the impact on plasma antioxidant status, low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Also, the functionality of HDL from the OSO-supplemented rats (OSO-HDL) was tested against carboxymethyllysine (CML)- induced hyperinflammation in embryo and adult zebrafish. The results revealed that four weeks of OSO supplementation (3 g/kg BW/day) had no adverse effect on rats' hematological and blood biochemical profiles. Nonetheless, decreased interleukin (IL)-6, and LDL-C levels, along with enhanced ferric ion reduction ability (FRA) and sulfhydryl content, were observed in the plasma of OSO-supplemented rats compared to the control and sunflower oil (SO) supplemented group. In addition, OSO supplementation stabilized apoA-I/HDL and augmented HDL-allied paraoxonase (PON)-1 activity. The microinjection of OSO-HDL (10 nL, 2 mg/mL) efficiently prevented the CML (500 ng)-induced zebrafish embryo mortality and developmental deformities. Similarly, OSO-HDL thwarted CML-posed neurotoxicity and demonstrated a significant hepatoprotective effect against CML-induced fatty liver changes, hepatic inflammation, oxidative stress, and apoptosis, as well as exhibiting a noticeable influence to revert CML-induced dyslipidemia. Conclusively, OSO supplementation demonstrated no toxic effects on rats, ameliorated plasma antioxidant status, and positively influenced HDL stability and functionality, leading to a protective effect against CML-induced toxicity in zebrafish.
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Background: High-density lipoprotein (HDL) plays an essential role in the immune system and shows effective antioxidative properties. We investigated correlations of lipid parameters with the sequential organ failure assessment (SOFA) score and the prognostic association with mortality in sepsis patients admitted to intensive care unit (ICU). Methods: We prospectively recruited consecutive adult patients with sepsis and septic shock, according to sepsis-3 criteria as well as non-sepsis ICU controls. Results: Fifty-three patients with sepsis (49% with septic shock) and 25 ICU controls without sepsis were enrolled. Dyslipidemia (HDL-C < 40 mg/l) was more common in sepsis compared to non-sepsis patients (85 vs. 52%, p = 0.002). Septic patients compared to controls had reduced HDL-C (14 vs. 39 mg/l, p < 0.0001), lower arylesterase activity of the antioxidative paraoxonase of HDL (AEA) (67 vs. 111 mM/min/ml serum, p < 0.0001), and a non-significant trend toward reduced cholesterol efflux capacity (9 vs. 10%, p = 0.091). We observed a strong association between higher AEA and lower risk of 28-day [per 10 mM/min/ml serum increase in AEA: odds ratio (OR) = 0.76; 95% CI, 0.61-0.94; p = 0.01) and ICU mortality (per 10 mM/min/ml serum increase in AEA: OR = 0.71, 95% CI, 0.56-0.90, p = 0.004) in the sepsis cohort in univariable logistic regression analysis. AEA was confirmed as an independent predictor of 28-day and ICU mortality in multivariable analyses. AEA discriminated well-regarding 28-day/ICU mortality in area under the receiver operating characteristic curve (AUROC) analyses. In survival analysis, 28-day mortality estimates were 40 and 69% with AEA ≥/< the 25th percentile of AEA's distribution, respectively (log-rank p = 0.0035). Conclusions: Both compositional and functional HDL parameters are profoundly altered during sepsis. In particular, the functionality parameter AEA shows promising prognostic potential in sepsis patients.
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The purpose of this study was to investigate the possible role of PON-1, an antioxidant lipophilic enzyme linked to HDL-C (high-density lipoprotein cholesterol), on the pathophysiology and clinical follow-up of acute pancreatitis. Biochemical tests, PON-1 and oxidative stress parameters (malonyl dialdehyde, MDA; superoxide dismutase, SOD; total antioxidant capacity, TAC) were evaluated in the sera of patients with acute pancreatitis at admission (day 0), day 3 and day 10 of follow-up, between June and September 2017. SPSS 13.0 statistical software package programme was used for statistical analyses.Mean age was 51.4 of the total 25 patients. Ranson scores were 0-1 points (60%), 3-4 points (24%) and 5-6 points (16%). CTSI (computed tomography severity index) scores were calculated, and most of the patients were seen to have mild or average pancreatitis (96%). While total cholesterol, triacylglycerol and LDL-C (low-density lipoprotein) levels stayed in their normal limits, there was a significant decrement tendency. HDL-C level was seen to rise significantly above its upper limit at day 10 (p < 0.001). Mean PON-1 levels were measured as 69.23, 76.72 vs. 113.15 U/mL at days 0, 3 and 10, respectively; and it was positively correlated with HDL-C (p < 0.001). Serum SOD increased also in parallel with PON-1 (20.49 vs. 39.46 U/mL) while MDA level decreased significantly (3.9 vs. 2.28 µM, p < 0.001). TAC was seen to rise significantly after treatment (0.52 vs. 1.22 mM). In conclusion, decreased PON-1 and HDL-C together with antioxidants SOD and TAC at the early period of acute pancreatitis were seen to rise after treatment, while the previously higher MDA level decreased in parallel. This reveals the importance of the balance between oxidative stress and antioxidant defense mechanisms in clinical progression of the disease, and the potential of PON-1 as a promising clinical marker.
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Antioxidantes/metabolismo , Arildialquilfosfatasa/sangre , Peroxidación de Lípido/fisiología , Estrés Oxidativo/fisiología , Pancreatitis/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Arildialquilfosfatasa/fisiología , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Pancreatitis/sangre , Proyectos Piloto , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Elevation of low-density lipoprotein (LDL) cholesterol is the hallmark of the dyslipidemia observed in hypothyroidism, but alterations on high-density lipoprotein (HDL) plasma levels and metabolism are less understood. The aim of this study was to explore aspects of HDL metabolism and enzymes that act on HDL after a short period of overt hypothyroidism. METHODS: Eighteen women (age 44 ± 11 years; body mass index 27.9 ± 5.2 kg/m2) were studied before total thyroidectomy for thyroid cancer, when they were euthyroid, and after thyroidectomy, in overt hypothyroidism for three weeks, following levothyroxine withdrawal for performance of a whole-body scan. RESULTS: Thyrotropin and free thyroxine confirmed hypothyroidism; low thyroglobulin and radioiodine uptake indicated near absence of thyroid tissue. LDL cholesterol (125 ± 35 vs. 167 ± 40 mg/dL; p = 0.0002), HDL cholesterol (HDL-C; 39 ± 8 vs. 46 ± 10 mg/dL; p = 0.0025), non-HDL-C (149 ± 38 vs. 201 ± 46 mg/dL; p < 0.0001), unesterified cholesterol (53 ± 10 vs. 70 ± 16 mg/dL; p = 0.0003), apolipoprotein (apo) A-I (1.32 ± 0.19 vs. 1.44 ± 0.22 g/L; p < 0.04), and apo B (0.97 ± 0.25 vs. 1.31 ± 0.28 g/L; p < 0.0001) plasma concentrations were all higher in hypothyroidism compared to values in the euthyroid state, but triglycerides and Lp(a) were unchanged. There were no changes in HDL particle size and lipid composition, cholesteryl ester transfer protein and lecithin cholesterol acyltransferase concentrations and in paraoxonase-1 activity. Regarding the in vitro assay to estimate lipid transfer to HDL, there were no changes when comparing the euthyroid to the hypothyroid state, but when adjusted for HDL-C, the unesterified cholesterol (0.14 ± 0.03 vs. 0.11 ± 0.02; p < 0.0001), triglycerides (0.11 ± 0.02 vs. 0.09 ± 0.02; p < 0.0001), phospholipids (0.44 ± 0.09 vs. 0.40 ± 0.07; p = 0.0205), and esterified cholesterol (0.14 ± 0.03 vs. 0.13 ± 0.03; p = 0.0043) transfer to HDL were all diminished in hypothyroidism. CONCLUSIONS: In short-term hypothyroidism, HDL-C increased, but this did not increase the capacity of the HDL fraction to receive lipids or the activity of paraoxonase-1, the anti-oxidation enzyme associated to HDL.
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Hipotiroidismo/sangre , Lipoproteínas HDL/sangre , Hormonas Tiroideas/sangre , Neoplasias de la Tiroides/sangre , Adulto , Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Persona de Mediana Edad , Pruebas de Función de la Tiroides , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Triglicéridos/sangreRESUMEN
Evidences indicate that abnormal lipid metabolism and lipid peroxidation can affect the progression of complications in systemic lupus erythematosus (SLE) patients. Apolipoprotein E (ApoE) and paraoxonase-1 (PON1) play important role in lipid metabolism and protection of lipid peroxidation. The polymorphisms of ApoE and paraoxonase (PON1) L55M (Met < Leu) allele genes lead to disorders in lipid metabolism and are related to atherosclerosis. This study is the first investigation to examine the possible association between ApoE and PON1-L55M polymorphisms and correlation with serum arylesterase (ARE) activities of PON, levels of malondialdehyde (MDA), neopterin, and lipid lipoprotein in SLE patients from Iranian western population. The present case-control study consisted of 107 SLE patients and 101 gender- and age-matched, unrelated, healthy controls from Iran's western population. The ApoE and PON1-L55M genotypes were identified using PCR-RFLP method. The serum level of MDA, neopterin, lipid levels, and ARE activity were determined by HPLC, commercial kits, and spectrophotometry, respectively. Our results showed that ApoE ε4 and PON1-55M alleles act synergistically to increase the risk of SLE by 1.47 times (p = 0.038). We found that the frequency of ApoE Æ3/Æ4 genotype was higher in SLE patients (11.2%) compared with control subjects (5%), although the difference was not significant (p = 0.087). This study for the first time not only demonstrates that ApoE Æ4 and PON-55M alleles synergistically increase the risk of SLE but also reveals that serum levels of MDA, neopterin, and LDL-C are high in SLE patients. This information may be in value for evaluating SLE progression and in the elucidation of the mechanisms of the disease pathogenesis.
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Alelos , Apolipoproteína E4/genética , Arildialquilfosfatasa/genética , Predisposición Genética a la Enfermedad , Lupus Eritematoso Sistémico/genética , Adulto , Hidrolasas de Éster Carboxílico/sangre , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Irán , Lupus Eritematoso Sistémico/sangre , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Neopterin/sangre , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
Abstract Background Oxidative and nitrosative stress pathways, along with immune-inflammatory response, might play an important role in the pathogenic mechanisms underlying major depression and bipolar disorder. Objective The aim of the present study is to investigate paraoxonase 1 polymorphisms and its correlations with disease parameters in patients with major depression and bipolar affective disorder. Methods PON1 L55M and Q192R single nucleotide polymorphisms were analyzed in a group consisted of 100 patients with major depression, and 100 patients with bipolar affective disorder and 96 healthy controls. Polymorphisms were analyzed by using polymerase chain reaction. Results Our findings reported no association between Q192R and L55M polymorphisms of PON1 and major depression and bipolar disorder. Additionally, there was no association between the PON1 genotypes and disease variables in both depressed and bipolar patients. Discussion Evaluating the different stages of patients with affective disorders and and investigating the connection between PON1 polymorphisms and treatment outcomes will help us to clarify the relationship between PON1 and mood disorders.
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BACKGROUND: Activated immune-inflammatory pathways play an important role in the pathophysiology of schizophrenia. Paraoxonase 1 (PON1) activity is inversely associated with inflammatory responses in numerous clinical conditions. The aims of this study were to delineate serum arylesterase PON1 activity in drug-naïve first episode psychosis (FEP) patients and a healthy control group, and to assess whether there are inverse relationships between PON1 activity and cytokine levels. METHODS: A total of 51 drug-naïve FEP patients and 61 healthy controls were enrolled in this study. Levels of interleukin (IL)-4, IL-10, IL-6, tumor necrosis factor (TNF)-α and activity of PON1 were quantified. RESULTS: Compared to healthy controls, FEP patients showed lower serum PON1 activity and higher levels of IL-4, IL-10 and TNF-α. A significant inverse relationship between PON1 activity and IL-4, IL-6 and IL-10 levels was detected, but not for TNF-α. Subjects with very low PON1 activity (25th quartile) presented significantly higher levels of IL-6, IL-10 and IL-4 than those with higher PON1 activity (75th quartile). CONCLUSION: The present study provides evidence that FEP is characterized by an inverse relationship between lowered activity of the anti-inflammatory/antioxidant enzyme PON1 and increased cytokine levels, including IL-6, IL-4 and IL-10. It is hypothesized that lowered PON1 activity may play a role in the immune-inflammatory response that accompanies FEP and that increased cytokine levels may further modulate PON1 activity.
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Arildialquilfosfatasa/sangre , Citocinas/sangre , Esquizofrenia/sangre , Esquizofrenia/enzimología , Enfermedad Aguda , Adolescente , Adulto , Biomarcadores/sangre , Femenino , Humanos , Modelos Lineales , Masculino , Análisis Multivariante , Esquizofrenia/inmunología , Factor de Necrosis Tumoral alfa , Adulto JovenRESUMEN
OBJECTIVE: This study aimed to investigate the variations of paraoxonase 1 (PON1) activity and lipid profile in patients with schizophrenia and the association of this activity with the sociodemographic, clinical and therapeutical characteristics of this population. PATIENTS AND METHODS: Our cross-sectional study included 140 schizophrenic patients and 119 control subjects aged respectively 37.3±10.4 and 41.4±10 years. PON1 activity was determined using Konelab 30™ equipment (Thermo Electron Corporation). Plasma total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (c-HDL) and low-density lipoprotein cholesterol (c-LDL) concentrations were determined using Cobas 6000™ (Roche Diagnostics), apolipoproteins (ApoA1, ApoB) and lipoprotein (a) (Lp(a)) were determined using Integra 400 plus (Roche Diagnostics). RESULTS: Compared to controls, patients had no significant decrease of PON1 activity and significantly lower ApoA1, c-HDL levels, and significantly higher levels of TG, ApoB, Lp(a) and TC/c-HDL and ApoB/ApoA1 ratios. Furthermore, PON1 activity was correlated with TG/c-HDL ratio. The lowest PON1 activity was noted in obese patients, in paranoid sub-type and in patients treated with combination of typical and atypical antipsychotics without significant difference. Moreover, it was associated with gender and cigarette smoking but not with alcohol consumption status. CONCLUSION: Schizophrenic patients had a decrease in PON1 activity and perturbations in their lipid profiles that contribute to increase the risk of cardiovascular diseases. In addition, our results revealed that there was no association between the decrease of PON1 activity and any demographic or clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile.
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Arildialquilfosfatasa/metabolismo , Lípidos/sangre , Esquizofrenia/sangre , Esquizofrenia/enzimología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
There is some evidence indicating lipid peroxidation can affect progression of atherosclerosis, cardiovascular diseases (CVDs) and glomerulonephritis in systemic lupus erythematosus (SLE) patients. Human butyrylcholinesterase (BuChE) and paraoxonase-1 (PON1) are two major bioscavenger enzymes that are associated with inflammation, oxidative stress and lipid metabolism. Hyperlipidemia, increase in lipid oxidation reactions and defects in antioxidant status may lead to increased oxidative stress and high frequency of CVDs in SLE. It has also been suggested that deficiency in the function of the antioxidant system and an increase in reactive oxygen release (ROS) may play an important role in the pathogenesis of SLE. This study is the first investigation to examine the association of BuChE phenotypes, PON1 (L55M; PON-55-M) polymorphism, the levels of malondialdehyde (MDA), neopterin, lipid-lipoprotein and activities of BuChE and arylesterase activity (ARE) of PON with severity of SLE. The present case-control study consisted of 109 SLE patients and 101 gender- and age-matched, unrelated healthy control subjects from the population of west Iran. We found that the PON-55-M allele and BuChE non-UU act synergistically to increase the risk of SLE by 2.5 times (1.03-6.7, p = 0.044). There was a significant negative correlation between severity of SLE with serum BuChE activity (R = -0.31, p < 0.001) and positive correlation with serum neopterin level. The SLE patients with the PON-55-M (M/L + M/M) allele or with BuChE non-UU phenotype had significantly lower serum ARE and BuChE activities than those with PON-55-L/L or BuChE-UU phenotypes, respectively. In addition, their serum levels of MDA, neopterin and LDL-C were significantly elevated, suggesting that these individuals are more susceptible to CVD. However, further studies are needed to shed more light on the contribution of the M allele of PON1 and non-UU phenotypes of BuChE in the development of SLE in different ethnicities.