Paraoxonase Activity Research Articles

Echinacea purpurea extract intervention for counteracting neurochemical and behavioral changes induced by bifenthrin

This study was conducted to elucidate the possible protective efficiency of Echinacea purpurea hydroethanolic extract (EchEE) against bifenthrin (BIF)-induced neuro-chemical and behavioral changes in rats. Total phenolics content, reducing power and radical scavenging activity of EchEE were estimated. Four groups of adult male albino rats were used (10 rats each) as follows: 1) Control healthy rats ingested with placebo, 2) Healthy rats orally received EchEE (465 mg/kg/day), 3) Rats intoxicated with BIF (7mg/kg/day) dissolved in olive oil, and 4) Rats co-treated with EchEE (465 mg/kg/day) besides to BIF (7mg/kg/day) intoxication. After 30 days, some neuro-chemical and behavioral tests were assessed. The behavioral tests revealed that rats received BIF exhibited exploratory behavior and spatial learning impairments, memory and locomotion dysfunction, and enhanced anxiety level. Biochemical findings revealed that BIF induced-oxidative stress in the cortex and hippocampus; this was appeared from the significant rise in malondialdehyde (MDA) and nitric oxide (NO) levels, coupled with decreased catalase (CAT), superoxide dismutase (SOD), paraoxonase-1 (PON-1) activities, and reduced glutathione (GSH) level in both brain areas. Also, BIF induced a significant increase caspas-3, tumor necrosis factor alpha (TNF), and interleukin-1beta (IL-1ß) in both areas; dopamine and serotonin levels, and ACh-ase activity were markedly decreased in both areas. Interestingly, treatment of rats with EchEE in combination with BIF resulted in a significant decrease in oxidative stress damage, and modulation of the apoptotic and pro-inflammatory markers. Also, EchEE markedly improved behavioral activities and neurotransmitters level that were impaired by BIF. In conclusion, the present study clearly indicated that EchEE can attenuate brain dysfunction induced by pesticides exposure through preventing the oxidative stress. This may be attributed to its high antioxidant component.

Pediatric nephrotic syndrome: The interplay of oxidative stress and inflammation.

The pathophysiological mechanisms crucial in the development of nephrotic syndrome (NS) in the pediatric population are still not fully understood. This study aimed to investigate the relationship between hypertension, oxidative stress, and inflammation in pediatric patients during the acute phase of the disease. The study included 33 children, aged 2 to 9 years, with nephrotic syndrome. Blood samples were collected during the acute phase and remission. Parameters of oxidative status were determined, including total oxidative status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), sulfhydryl groups (-SH), paraoxonase 1 (PON1), and total antioxidant status (TAS) in serum, measured spectrophotometrically. Inflam - matory parameters such as pentraxin 3 (PTX3), leptin, program med cell death ligand 1 (PD-L1), and E-cadherin were determined using enzyme-linked immunosorbent assay (ELISA). Patients with nephrotic syndrome and hypertension had significantly higher levels of advanced oxidation protein products and total antioxidant status (p=0.029 and p=0.003, respectively). During the acute phase of the disease, lower activity of sulfhydryl groups and paraoxonase 1 was observed compared to remission (p<0.001, for both). Pentraxin 3 levels were higher, while leptin levels were lower during the acute phase (p<0.001, for both). Pentraxin 3 correlated with advanced oxidation protein products and total antioxidant status during the acute phase but not in remission (rs=0.42, p=0.027 and rs=0.43, p=0.025, respectively). A negative correlation between Advanced oxidation protein products and leptin was observed during the acute phase, which disappeared in remission (rs=-0.42, p=0.028). Results of this study show that hypertension influences oxidative stress markers, and decreased antioxidant capacity may contribute to nephrotic syndrome development. Pentraxin 3 appears as a potential disease activity marker, indicating a dynamic connection between inflammation and oxidative stress. Leptin may also play a role in oxidative stress in nephrotic syndrome.

Signature of paraoxonases in the altered redox homeostasis in Alzheimer's disease

Paraoxonase (PON) enzymes (PON1, PON2 and PON3) exert antioxidant properties through arylesterase, lactonase and paraoxonase activities. Increasing findings suggested their potential involvement, particularly PON1 and PON2, in Alzheimer's disease (AD), a neurodegenerative pathology characterized by early oxidative stress. Specifically, decreased serum PON1-arylesterase and lactonase activities seem to be associated with an increased brain oxidative damage in early AD, leading to hypothesize that PON activity alterations might be an early event in AD. To address this hypothesis, the levels of 4-hydroxynonenal (4-HNE; i.e. a marker of oxidative stress damage) along with the protein expression and enzymatic activity of PON1 and PON2 have been investigated in the brain and serum of young [Postnatal day (PD)8–10, 20–25 and 60–65] asymptomatic 3xTg-AD female mice, one of the most used transgenic models of AD.At PD 8–10, there were no differences in hippocampus and prefrontal cortex (PFC) 4-HNE expression levels between 3xTg-AD mice compared to controls (Non-Tg mice). On the other hand, significant increased levels of 4-HNE were detected in PD 20–30 3xTg-AD mice hippocampus, while a significant reduction was observed in 3xTg-AD group at PD 60–65. In the PFC, 4-HNE levels were significantly reduced in 3xTg-AD mice brain at PD 20–30, while no differences in 4-HNE levels were detected at PD 60–65.No significant differences in arylesterase and lactonase activities were observed in the plasma of 3xTg-AD and Non-Tg mice at the different considered ages. Compared to Non-Tg mice, a reduction of brain arylesterase activity was found in 3xTg-AD female at PD 20–30 and PD 60–65, but it was significant only in the younger group. Finally, a similar trend was observed also for PON1 and PON2 protein levels, with both significantly, and solely, decreased in 3xTg-AD mice brain at PD 20–30.Overall, these findings suggest that the altered oxidative stress homeostasis in the 3xTg-AD female mice may be related to an early reduction in activity and expression of PONs enzymes most likely via a reduced brain arylesterases activity.

Unveiling the therapeutic potential of a mutated paraoxonase 2 in diabetic retinopathy: Defying glycation, mitigating oxidative stress, ER stress and inflammation

Paraoxonase 2 (PON2) is an intracellular anti-oxidant protein ubiquitously expressed in all cells and reduces reactive oxygen species, endoplasmic reticulum (ER) stress, further improves mitochondrial function and thereby shows anti-apoptotic function. In diabetes and its complications this PON gets glycated and becomes in effective. The PON activity is reported to be reduced in diabetic retinopathy and we have earlier showed Carboxy methyl lysine (AGE) decreased PON2 expression and activity in Human retinal endothelial cells (HREC) . In this study, we have designed and developed a mutated PON2 by in silico and in vitro approach which can resist glycation. Where in glycation-prone residues in PON2 was predicted using in silico analyses and a mutated PON2 was developed using in vitro site directed mutagenesis (SDM) assay mPON2 (mutant PON2-PON2-K70A) and its efficacy was compared with wPON2 (wild type PON2). CML glycated wPON2 and reduced its activity when compared with mPON2 in HREC confirmed by immunoprecipitation and in vitro experiments. Additionally, mPON2 interaction efficiency with its substrates was higher than wPON2 by insilico assay and demonstrated enhanced inhibition against CML-induced oxidative stress, ER stress, pro-inflammation, and mitochondrial fission than wPON2 by invitro assay. Further mPON2 showed increased inhibition of phosphorylation of NFĸB induced by CML. Our investigation establishes that the over expression of mPON2 in HREC can defy glycation and therefore mitigate ER stress and inflammation against CML than endogenous wPON2. These findings imply that mPON2 can be a beneficial therapeutic target against diabetic retinopathy.

Exploring the chondroitin sulfate nanogel's potential in combating nephrotoxicity induced by cisplatin and doxorubicin—An in-vivo study on rats

In this study, we aim to unveil the potential of itaconyl chondroitin sulfate nanogel (ICSNG) in tackling chronic kidney diseases triggered by the administration of CDDP and doxorubicin (Adriamycin, ADR). To that end, the new drug delivery system (ICSNG) was initially prepared, characterized, and loaded with the target drugs. Thereafter, the in-vivo studies were performed using five equally divided groups of 100 male Sprague-Dawley (SD) rats. Biochemical evaluation and immunohistochemistry studies have revealed the renal toxicity and the ameliorative effects of ICSNG on renal function. When ICSNG-based treatments were contrasted with the CDDP and ADR infected groups, they significantly increased paraoxonase-1 (PON-1), superoxide dismutase (SOD), catalase (CAT) and albumin activity and significantly decreased nitric oxide (NO), tumor necrosis factor alpha (TNF-α), creatinine, urea, and cyclooxygenase-2 (COX-2) activity (p < 0.001). The findings of the current study imply that ICSNG may be able to lessen renal inflammation and damage in chronic kidney disorders brought on by the administration of CDDP and ADR. Interestingly, according to the estimated selectivity indices, the ICSNG-encapsulated drugs have demonstrated superior selectivity for cancer MCF-7 cells, over healthy HSF cells, in comparison to the bare drugs.

The protective effects of betanin on titanium dioxide (TiO2) nanoparticle exposure in rats

The aim of this study was to investigate the protective properties of betanin in rats exposed to Titanium dioxide (TiO2) nanoparticles. An experimental animal study was conducted on 40 Spraque Dawley rats. The rats were studied in 4 groups (n = 10). Group I: Control group, Group II: TiO2 group (250 mg/kg/bw), Group III: TiO2 + Betanin group (250 mg/kg/bw TiO2 + Betanin; 100 µg/ml), Group IV: Betanin group (100 µg/ml). After 28 days of application, blood and liver tissue samples of the rats were collected. Total Antioxidant Status (TAS, mmol Trolox Eq/L), Total Oxidant Status (TOS, µmol H2O2 Eq/L), Paraoxonase (PON, U/L), Total thiol (μmol/L), Nitric oxide (NO, µmol/L), Malondialdehyde (MDA, nM/ml) and Catalase (CAT, U/mg protein) activity levels in the blood and liver tissue measured. Liver tissue samples were evaluated by immunohistochemical methods (Caspase-3 and 8-Hydroxy-2'-deoxyguanosine) and hematoxylin-eosin staining. As a result, a significant (p < 0.001) increase in the mean oxidant parameters and a significant (p < 0.001) decrease in the antioxidant parameters were determined in the TiO2 group when compared to the control group. Caspaze-3 and 8-OHdG histopathological results findings indicated a similar situation. However, it was determined that TiO2 damage was significantly reduced (p < 0.001) in rats to which TiO2 and betanin were administered together. In addition, the highest antioxidant levels and low histopathological damage were determined among all groups in the betanin-only group. Betanin (C24H26N2O13) shows protective activity in oxidative tissue damage caused by TiO2 nanoparticles.

Enhancement of Antioxidant and Anti-Glycation Properties of Beeswax Alcohol in Reconstituted High-Density Lipoprotein: Safeguarding against Carboxymethyllysine Toxicity in Zebrafish.

The antioxidant and anti-inflammatory abilities of beeswax alcohol (BWA) are well reported in animal and human clinical studies, with a significant decrease in malondialdehyde (MDA) in the blood, reduced liver steatosis, and decreased insulin. However, there has been insufficient information to explain BWAs in vitro antioxidant and anti-inflammatory activity owing to its limited solubility in an aqueous buffer system. Herein, three distinct reconstituted high-density lipoproteins (rHDL) were prepared with palmitoyloleoyl phosphatidylcholine (POPC), cholesterol, apolipoprotein A-I (apoA-I), and BWA at molar ratios of 95:5:1:0 (rHDL-0), 95:5:1:0.5 (rHDL-0.5), and 95:5:1:1 (rHDL-1) and examined for antioxidant and anti-glycation effects. A rHDL containing BWA, precisely rHDL-1, displayed a remarkable anti-glycation effect against fructose (final 250 mM), induced glycation of HDL, and prevented proteolytic degradation of apoA-I. Also, BWA incorporated rHDL-0.5, and rHDL-1 displayed substantial antioxidant activity by inhibiting cupric ion-mediated low-density lipoprotein (LDL) oxidation. In contrast to rHDL-0, a 20 and 22% enhancement in ferric ion reduction ability (FRA) and paraoxonase (PON) activity was observed in HDL treated with rHDL-1, signifying the effect of BWA on the antioxidant activity enhancement of HDL. rHDL-1 efficiently inhibits Nε-carboxylmethyllysine (CML)-induced reactive oxygen species (ROS) generation and apoptosis in zebrafish embryos, consequently improving embryo survivability and developmental deformities impaired by the CML. The dermal application of rHDL-1 to the CML-impaired cutaneous wound of the adult zebrafish inhibited ROS production and displayed potent wound-healing activity. Conclusively, incorporating BWA in rHDL significantly enhanced the anti-glycation and antioxidant activities in rHDL via more stabilization of apoA-I with a larger particle size. The rHDL containing BWA facilitated the inherent antioxidant ability of HDL to suppress the CML-induced toxicities in zebrafish embryos and ameliorate CML-aggravated chronic wounds in adult zebrafish.

Investigation of serum ischemic-modified albumin, galectin-3, paraoxonase-1, and myeloperoxidase activity levels in patients with acute brucellosis

ABSTRACTObjectives:Infection remains current as an important discussion topic in the etiological factors of atherosclerosis. Ischemic-modified albumin (IMA), galectin-3 (gal-3), paraoxonase-1 (PON-1), and myeloperoxidase (MPO) are biomolecules that play an important role in the pathogenesis of atherosclerosis. Our aim is to investigate serum IMA, gal-3, PON-1, and MPO activity in acute brucellosis infection.Materials and Methods:Forty patients with acute brucellosis and 40 healthy individuals were included in the study. Serum IMA, gal-3, PON-1, and MPO activity were analyzed by the ELISA method.Results:In acute brucellosis infection, serum gal-3, IMA, and MPO activities were found to be significantly increased compared to the control group, and PON-1 activity was found to be significantly decreased compared to the control group (p < 0.001). There was a positive correlation between serum IMA, and MPO activity (r = 0.707 p = 0.000) and a negative correlation (r = −0.943, p = 0.000) between PON-1 activity. There was a positive correlation between serum gal-3 and MPO activity (r = 0.683, p = 0.000) and IMA level (r = 0.927, p = 0.000) and a negative correlation between PON-1 activity (r = −0.951, p = 0.000).Conclusion, it was found that serum gal-3, IMA levels and MPO activity increased, while PON-1 activity decreased. These results showed that the oxidant-anti-oxidant balance is impaired in acute brucellosis infection. In addition, these results indicate that brucella infection may be increase the risk of atherosclerosis. Further studies are needed to support our findings.

Thymus atlanticus (Ball) Roussine Aqueous Extract Exerts Lipid-lowering and Anti-atherosclerotic Effects in Hyperlipidemic Guinea Pigs.

Thymus atlanticus (Ball) Roussine (T. atlanticus) is traditionally used in the Moroccan high Atlas Mountains to treat several disorders, including cardiovascular disease. In the present study, the lipid-lowering and anti-atherosclerotic activities of the traditionally used aqueous extract of T. atlanticus were evaluated on guinea pigs subjected to chronic hyperlipidemia. Animals were given a diet containing 2% cholesterol and 20% lard for 12 weeks. Moreover, thyme extract was given daily at 400 mg/kg. At the end of the experiment, lipid levels and paraoxonase arylesterase activity were measured, and aorta histology was studied. Our findings revealed that there was an important elevation of blood lipids in the HFD group along with a significant decrease in paraoxonase arylesterase activity (-40.06%). Moreover, the consumption of fat altered the histology of aorta by thickening the intima media and forming atherosclerotic lesions and foam cells in these tissues. However, the administration of thyme extract attenuated HFD-caused alterations by decreasing blood lipids, elevating paraoxonase activity (+24.04%), and limiting the progression of atherosclerotic lesions. We conclude that the supplementation with the aqueous extract of T. atlanticus could potentially protect against hyperlipidemia and consequently, the development of atherosclerosis.

Transfer Proteins, Lipoprotein Remodeling, and Antioxidant Action on Pregnant Women: Comparison from the First to the Third Trimester of Gestation

Introduction: During pregnancy, maternal lipid metabolism undergoes several transformations originated by hormonal changes. There are two distinct phases: initial and late, finally driven to hypertriglyceridemia. Maternal hyperlipidemia, especially hypertriglyceridemia, is associated with an increased hepatic very-low-density lipoprotein (VLDL) synthesis stimulated by high estrogen levels during gestation. Objectives: This study aimed to evaluate the action of possible lipoproteins remodeling modulators, such as phospholipid and cholesteryl-ester transfer proteins (PLTP and CETP), paraoxonase-1 (PON-1), and apolipoproteins (apo), during gestation. Methods: An observational prospective cohort study composed of 40 pregnant women was conducted. Blood samples were collected in two moments: at the first and third trimesters of gestation, followed by the biochemical determination of apo A-I, apo B, lipid profile, PON-1, PLTP and CETP activities, and HDL particle size. Results: The majority of pregnant women in the third trimester showed dyslipidemia, mainly hypertriglyceridemia. In the third trimester of gestation, we observed an increase in CETP activity (70.5 ± 9.6 pmol/µL/h; p &lt;0.001) and TG/HDL-C ratio (2.7 [2.0-3.8]), but on the other hand, PON-1 activity (65.4 [46.5-105] nMol of p-nitrophenol/min/mL) decreased. High-density level lipoprotein (HDL) particle size and PLTP activity did not differ in the two studied moments. The serum triglyceride concentration and CETP activity showed a positive linear correlation in the first trimester of gestation (r2=0.65, p&lt;0.001). Conclusion: Data suggest that the CETP activity, antioxidant profile, and low-density lipoprotein (LDL) remodeling are modified by physiological metabolic changes during an uncomplicated gestational period.

Oxidative stress induction by OCPs and OPPs pesticides may cause lung cancer incidence

Background and aims Pesticides are nowadays known as one of the most important causes of human disorders worldwide. The aim of the present study was to investigate the role of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in the development of lung cancer. Methods We determined the levels of seven derived OCP residues (α-HCH, β-HCH, γ-HCH, 2,4 DDT, 4,4 DDT, 2,4 DDE, and 4,4 DDE) and enzymatic antioxidant biomarkers including paraoxonase-1 (PON-1), erythrocyte’s acetylcholinesterase (AChE), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and non-enzymatic antioxidant biomarkers, including total antioxidant capacity (TAC), protein carbonyl (PC), malondialdehyde (MDA), and nitric oxide (NO) in the blood samples of 51 lung cancer patients and 51 healthy subjects as controls. Furthermore, the effects of OPP exposure on the development of lung cancer and oxidative stress (OS) are indirectly assessed by measuring AChE and PON-1 enzyme activities. Results The average values of all the measured OCPs were significantly higher in lung cancer patients when compared with healthy control subjects (p < 0.05). AChE, PON-1, GPx, and CAT activity levels, as well as the amounts of PC, MDA, and NO were higher in patients with lung cancer than in the control subjects (p < 0.05), while TAC values were lower in the patients. Moreover, our data showed a significant association between OCP concentrations and OS parameters (p < 0.05). Conclusion The results suggest that OCPs and OPPs may have a role in lung cancer incidence in southeastern Iran, and at least one of the mechanisms by which OCPs and OPPs may contribute to increasing the development of lung cancer in the studied area is through OS generation.

Serum Arylesterase, Paraoxonase, and Lactonase Activities and Paraoxonase-1 Concentrations in Morbidly Obese Patients and Their Relationship with Non-Alcoholic Steatohepatitis.

Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = -0.24, p < 0.001, and rho = -0.30, p < 0.001, respectively) and body mass index (rho = -0.15, p = 0.001, and rho = -0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies.

Regular Practice of Physical Activity Improves Cholesterol Transfers to High-Density Lipoprotein (HDL) and Other HDL Metabolic Parameters in Older Adults

The effects of regular physical activity on two important anti-atherosclerosis functions of high-density lipoprotein (HDL), namely its capacity to receive both forms of cholesterol and its anti-oxidant function, were investigated in this study comparing older adults with young individuals. One-hundred and eight healthy adult individuals were enrolled and separated into the following groups: active older (60–80 yrs, n = 24); inactive older (60–79 yrs, n = 21); active young (20–34 yrs, n = 39); and inactive young (20–35 yrs, n = 24). All performed cardiopulmonary tests. Blood samples were collected in order to assess the following measures: lipid profile, HDL anti-oxidant capacity, paraoxonase-1 activity, HDL subfractions, and lipid transfer to HDL. Comparing active older and active young groups with inactive older and inactive young groups, respectively, the active groups presented higher HDL-C levels (p &lt; 0.01 for both comparisons), unesterified cholesterol transfer (p &lt; 0.01, p &lt; 0.05), and intermediate and larger HDL subfractions (p &lt; 0.001, p &lt; 0.01) than the respective inactive groups. In addition, the active young group showed higher esterified cholesterol transfer than the inactive young group (p &lt; 0.05). As expected, the two active groups had higher VO2peak than the inactive groups; VO2peak was higher in the two younger than in the two older groups (p &lt; 0.05). No differences in unesterified and esterified cholesterol transfers and HDL subfractions were found between active young and active older groups. HDL anti-oxidant capacity and paraoxonase-1 activity were equal in all four study groups. Our data highlight and strengthen the benefits of regular practice of physical activity on an important HDL function, the capacity of HDL to receive cholesterol, despite the age-dependent decrease in VO2peak.

Structural Characteristics of PON1 with Leu55Met and Gln192Arg Variants Influencing Oxidative-Stress-Related Diseases: An Integrated Molecular Modeling and Dynamics Study.

Background and Objectives: PON1 is a multi-functional antioxidant protein that hydrolyzes a variety of endogenous and exogenous substrates in the human system. Growing evidence suggests that the Leu55Met and Gln192Arg substitutions alter PON1 activity and are linked with a variety of oxidative-stress-related diseases. Materials and Methods: We implemented structural modeling and molecular dynamics (MD) simulation along with essential dynamics of PON1 and molecular docking with their endogenous (n = 4) and exogenous (n = 6) substrates to gain insights into conformational changes and binding affinity in order to characterize the specific functional ramifications of PON1 variants. Results: The Leu55Met variation had a higher root mean square deviation (0.249 nm) than the wild type (0.216 nm) and Gln192Arg (0.202 nm), implying increased protein flexibility. Furthermore, the essential dynamics analysis confirms the structural change in PON1 with Leu55Met vs. Gln192Arg and wild type. Additionally, PON1 with Leu55Met causes local conformational alterations at the substrate binding site, leading to changes in binding affinity with their substrates. Conclusions: Our findings highlight the structural consequences of the variants, which would increase understanding of the role of PON1 in the pathogenesis of oxidative-stress-related diseases, as well as the management of endogenous and exogenous chemicals in the treatment of diseases.

The Modulatory Bioeffects of Pomegranate (Punica granatum L.) Polyphenols on Metabolic Disorders: Understanding Their Preventive Role against Metabolic Syndrome

Modern research achievements support the health-promoting effects of natural products and diets rich in polyphenols. Pomegranate (PG) (Punica granatum L.) contains a considerable number of bioactive compounds that exert a broad spectrum of beneficial biological activities, including antimicrobial, antidiabetic, antiobesity, and atheroprotective properties. In this context, the reviewed literature shows that PG intake might reduce insulin resistance, cytokine levels, redox gene expression, blood pressure elevation, vascular injuries, and lipoprotein oxidative modifications. The lipid parameter corrective capabilities of PG-ellagitannins have also been extensively reported to be significantly effective in reducing hyperlipidemia (TC, LDL-C, VLDL-C, and TAGs), while increasing plasma HDL-C concentrations and improving the TC/HDL-C and LDL-C/HDL-C ratios. The health benefits of pomegranate consumption seem to be acheived through the amelioration of adipose tissue endocrine function, fatty acid utilization, GLUT receptor expression, paraoxonase activity enhancement, and the modulation of PPAR and NF-κB. While the results from animal experiments are promising, human findings published in this field are inconsistent and are still limited in several aspects. The present review aims to discuss and provide a critical analysis of PG’s bioeffects on the components of metabolic syndrome, type-2 diabetes, obesity, and dyslipidemia, as well as on certain cardiovascular-related diseases. Additionally, a brief overview of the pharmacokinetic properties, safety, and bioavailability of PG-ellagitannins is included.

Serum oxidant–antioxidant status and butyrylcholinesterase activity in dogs with idiopathic epilepsy – A pilot study

Oxidative stress plays an important role in pathogenesis of idiopathic epilepsy (IE). Although IE is the most common neurological condition, oxidant–antioxidant status in epileptic dogs is still unknown. The aim of this study is to evaluate the serum oxidant-antioxidant status in dogs with newly diagnosed IE. The status in 15 dogs with IE and 15 healthy dogs is estimated through spectrophotometric determination of two oxidant markers: advanced oxidation protein products-albumin index (AOPP) and thiobarbituric acid reactive substances (TBARS); and three antioxidant markers: total thiols (R-SH) level, glutathione (GSH) level, and paraoxonase-1 (PON-1) activity. Also, butyrylcholinesterase (BChE) activity is assessed in both groups of dogs. Higher AOPP is observed in the dogs with newly diagnosed IE, while TBARS level shows no difference when compared to the healthy dogs. In contrast, lower levels of antioxidants (R-SH, GSH, and PON-1) and BChE activity are found in the dogs with IE. No significant differences are observed in the oxidant and antioxidant markers and BChE activity across the investigated IE cases with focal and generalized seizures. Our findings provide evidence that dogs with IE are characterized by an impaired serum oxidant–antioxidant balance and lower BChE activity, which may contribute to a better understanding of IE pathogenesis.

Pesticide Exposure and Alzheimer's Disease: A Case-control Study.

63 AD patients and 50 healthy individuals participated, and the levels of some OCPs derivatives (including; α-HCH, β-HCH, γ-HCH, 2,4-DDT, 4,4-DDT, 2,4-DDE, and 4,4-DDE), total antioxidant capacity (TAC), protein carbonyl (PC), malondialdehyde (MDA), Nitric oxide (NO) along with the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), paraoxonase 1(PON1), and acetylcholinesterase (AChE) were measured. The mean OCP level of OCPs in AD patients was significantly higher than in the control group. However, the patients' mean levels of TAC, PC, MDA and activity of SOD, GPx, PON1 and AChE were significantly lower than controls. A significant positive correlation was also observed between 2,4-DDE and MDA and between γ-HCH and PC in AD patients. These findings showed that pesticide exposure is associated with an increased risk of AD. Furthermore, the mean levels of oxidative stress markers, which may result from pesticide exposure, were significantly lower in AD patients compared to healthy individuals. Therefore, it may conclude that pesticides, at least in part, contribute to AD development through several mechanisms, including the induction of oxidative stress.

A Nutraceutical Compound Containing a Low Dose of Monacolin K, Polymethoxyflavones, Phenolic Acids, Flavonoids, and Hydroxytyrosol Improves HDL Functionality.

In earlier studies, it has been observed that 8-week treatment with a novel nutraceutical compound (NC) containing low monacolin K dose, polymethoxyflavones, phenolic acids, flavonoids, and hydroxytyrosol improves lipid profile and endothelial function and reduces the level of oxidized low-density lipoprotein (oxLDL). We hypothesize that this effect might be, at least in part, explained by positive modulation exerted by the NC on the atheroprotective function of high-density lipoprotein (HDL). This study aimed to evaluate whether the NC could influence determinants of HDL function. Forty-five subjects with low-moderate dyslipidaemia were enrolled and treated for 8 weeks with the NC, followed by 4 weeks of washout. Blood samples were collected at every time point to evaluate changes in lipid profile, endothelial function, oxLDL, and markers of HDL function, such as the anti-oxidant activities of paraoxonase-1, glutathione peroxidase-3 (Gpx3), lipoprotein-phospholipase A2 (Lp-PLA2), and pro-oxidant activity of myeloperoxidase (MPO). Although the concentration of HDL-C did not change, the activity of Lp-PLA2 significantly decreased upon treatment (-11.6%, p<0.001) and returned to baseline level 4 weeks after the end of treatment. In contrast, Gpx3 increased after treatment (+5%, p<0.01) and remained unvaried after 4 weeks. Both MPO activity and concentration significantly decreased after the washout period (-33 and 32%, p<0.001). For the first time, it was found that the administration of an NC with beneficial effects on lipid homeostasis also positively impacts HDL function by improving the balance between protective and damaging determinants. Further investigation is required to corroborate our findings.

Longitudinal changes of oxidative stress and PON1 lactonase activity and status in older pregnant women undergoing assisted reproductive technology: a prospective nested case-control study

BackgroundChildbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART.MethodsThis prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed.ResultsLactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups.ConclusionsWomen with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases.

The attraction of paraoxonase-1 associated with the MAPK pathway on colon carcinoma cells

Abstract Objectives A comprehensive understanding of the role of PON enzymatic activities may play an important role in the etiology and prevention of many cancers. PON1 is known as a potent antioxidant that scavenges free radicals in the human body. The enzymatic activities of paraoxonase (PON1) and mitogen-activated protein kinase (MAPK) signalling pathways in colorectal cancer are being investigated to determine whether they hold promise for novel diagnostic or therapeutic applications in colorectal cancer. Methods HT-29 colon cancer cell lines and CCD-18Co colon cell lines were used. B-Raf, p-B-Raf, ERK, and p-ERK proteins involved in MAPK signalling pathways and serum levels of PON1 were detected and analyzed by the Western blotting method. Results The levels and activity of PON1 enzyme were significantly decreased in HT-29 cells compared to CCD-18Co cells (p=0.0173 and p=0.0281, respectively). The levels of p-B-Raf and p-ERK, which activates the MAPK signalling pathway, were significantly increased in HT-29 cells (p=0.0037 and p=0.0074, respectively). Conclusions A positive correlation was found between PON1 level and PON1 enzyme activity (p=0.008). A negative correlation was found between PON1 level and p-B-Raf/p-ERK protein levels, which play a role in the MAPK signalling pathway (p=0.016 and p=0.036, respectively). A negative correlation was also found between PON1 enzyme activity and p-B-Raf/p-ERK protein levels (p=0.060 and p=0.037, respectively). It is suggested that the increase of proteins involved in the MAPK signaling pathway in cancer cells is caused by the decreasing serum levels of PON1 and enzymatic activity of PON1.