Serum Paraoxonase Activity Research Articles

Bayesian meta-analysis of inter-phenotypic differences in human serum paraoxonase-1 activity for chemical risk assessment

Human variability in paraoxonase-1 (PON1) activities is driven by genetic polymorphisms that affect the internal dose of active oxons of organophosphorus (OP) insecticides. Here, an extensive literature search has been performed to collect human genotypic frequencies (i.e. L55M, Q192R, and C-108T) in subgroups from a range of geographical ancestry and PON1 activities in three probe substrates (paraoxon, diazoxon and phenyl acetate). Bayesian meta-analyses were performed to estimate variability distributions for PON1 activities and PON1-related uncertainty factors (UFs), while integrating quantifiable sources of inter-study, inter-phenotypic and inter-individual differences. Inter-phenotypic differences were quantified using the population with high PON1 activity as the reference group. Results from the meta-analyses provided PON1 variability distributions and these can be implemented in generic physiologically based kinetic models to develop quantitative in vitro in vivo extrapolation models. PON1-related UFs in the Caucasian population were above the default toxicokinetic UF of 3.16 for two specific genotypes namely −108CC using diazoxon as probe substrate and, −108CT, −108TT, 55MM and 192QQ using paraoxon as probe substrate. However, integration of PON1 genotypic frequencies and activity distributions showed that all UFs were within the default toxicokinetic UF. Quantitative inter-individual differences in PON1 activity are important for chemical risk assessment particularly with regards to the potential sensitivity to organophosphates’ toxicity.

Teucrium leucocladum: An Effective Tool for the Treatment of Hyperglycemia, Hyperlipidemia, and Oxidative Stress in Streptozotocin-Induced Diabetic Rats.

Teucrium leucocladum is among the most used traditional medicinal plants in Palestine, which is used for the treatment of hyperglycemia and colon spasms from ancient times. Therefore, the current investigation aimed for the first time to determine the hypoglycemic, hypolipidemic, and oxidative stress inhibitory effects of the aerial parts (stem and leaves) of T. leucocladum hydrophilic (water) extract in streptozotocin- (STZ-) induced diabetic rats (65 mg/kg), given intraperitoneally at a dose of 100 mg/kg for 21 days. The rats were divided into four groups as control (C), control + T. leucocladum extract (C + TL), diabetes (D), and diabetes + T. leucocladum extract (D + TL). The antioxidant activity was analyzed using in vitro 2,2-diphenyl-1-picrylhydrazyl and in vivo methods by measuring the plasma and tissue malondialdehyde (MDA) levels using a colorimetric assay. On the other hand, glutathione peroxidase (GSH-Px), erythrocyte superoxide dismutase (SOD) enzyme levels, serum paraoxonase (PON), and arylesterase (ARE) enzyme activities were assessed by utilizing standard biochemical kits. Besides, the blood glucose and serum insulin levels were assessed by a glucometer and Rat ELISA Kit, respectively. However, the autoanalyzer was used to evaluate the lipid profile. The diabetic rat group that administered T. leucocladum extract showed the best reduction in the tissue and plasma MDA levels and an increase of insulin-releasing potentials. Besides, the serum PON and ARE activities and erythrocyte superoxide dismutase and whole blood glutathione peroxidase enzyme levels were significantly increased in all animals treated with T. leucocladum extract. The current investigation demonstrated that T. leucocladum manifests antihyperglycemic and antihyperlipidemic effects and also increased the antioxidative defense system and reduced the lipid peroxidation process in experimental diabetic rats.

Plasma albumin redox state is superior to conventional biomarkers to indicate the presence of potential protein undernutrition

AbstractThe redox state of plasma albumin would reflect albumin synthesis rate, and could be useful to demonstrate the presence of potential protein undernutrition. Aiming to delineate the characteristics of plasma albumin redox state as a nutritional biomarker, adult male Wistar rats were maintained on AIN-93M (14% casein, control diet) or an AIN-93M-based low protein diet (5% casein) ad libitum for 4 weeks, and the two groups were compared by examining plasma albumin redox state, plasma/serum levels of conventional biomarkers for protein nutritional status, and plasma proteome. While no significant difference was seen in body weight at the end of the experimental period, plantaris muscle mass trended lower in the low protein diet group, implicating the manifestation of moderate protein undernutrition. The redox of plasma albumin was shifted to more oxidized state in the low protein diet group, and the shift persisted during the entire experimental period. In contrast, the levels of conventional biomarkers, plasma albumin and prealbumin, were initially decreased in the low protein diet group, and the differences were then dissolved later in the experimental period. Similarly, the levels of other biomarkers, plasma transferrin and serum retinol-binding protein-4, did not differ significantly at the end of the experimental period. Plasma proteomic analysis revealed that the abundances of proteins that constitute high-density lipoprotein (HDL), apolipoprotein A-II and paraoxonase-1, were decreased in the low protein diet group, which were then validated by confirming decreases in plasma HDL level, plasma HDL-cholesterol level, and serum paraoxonase-1 activity in the low protein diet group. According to epidemiological reports, dietary protein intake is positively associated with plasma HDL-cholesterol level, and the risk factors of cardiovascular diseases, including lower HDL-cholesterol level, are closely related to frailty. Thus, it can be conceived that moderate dietary protein insufficiency would increase cardiovascular risks, such as reduction in HDL level and function (paraoxonase-1 activity), which could prime the onset of amyotropic diseases later in life, such as sarcopenia and frailty. Collectively, moderate dietary protein insufficiency would lead to decreased skeletal muscle mass, and also attenuate circulating HDL level and function, which could even aggravate the attenuation of skeletal muscle accretion; the redox state of plasma albumin would be instrumental over conventional biomarkers as an indicator of potentially protein undernourished status.

THE EFFECT OF ATORVASTATINUM IN THE TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS

The aim: Was to evaluate the effect of 6-month pathogenetic treatment in combination with atorvastatinum on the endothelium function, lipid and adipokine levels, paroxonase activity and activity of inflammatory process in RA patients. Materials and methods: The study included 55 patients with RA, dividing into two groups depending on the intended therapy. The first group included 33 patients with "traditional" treatment by methotrexate, glucocorticoids, and non-steroid anti-inflammatory drugs. The second group included 22 patients with "traditional" treatment and additionally prescribed of atorvastatinum 20 mg/day. The lipid profile, leptin, adipokine, paroxonase activity. C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) levels, FMDBA and IMT of carotid artery were determined in all participants of the study. Control parameters were recorded before the start, after 1 and 6 months of treatment. Results: The FMDBA has increased by 32% in the second group, compared by only 10.9% in the first group. The dynamics of IMT in the first group was also twice lower than in group with the additional use of atorvastatinum. The leptin levels in the second group significantly decreased by 27% and adiponectin levels increased by 12.8%, than in the first group - by 12.8% and by 7% respectively. The appointment of statins over 6 months resulted in DAS28, TNF-α, ESR and CRP reduction by 15%, 31%, 25% and 21.5% respectively. In the first group the dynamics of indicate rates ranged from 7.8% to 22.5%, and was significantly lower than in the second group. Conclusions: As a result of the study, it was found that the appointment of atorvastatinum 20 mg/day during 6 months not only reduces dyslipidemia, but also significantly reduces the inflammatory process and adipokine dysregulation, normalizes serum paraoxonase activity and improves the endothelium function.

Relationship between Paraoxonase-1 and Arylesterase Enzyme Activities and SYNTAX I and II Scores in Patients with ST-Elevation Myocardial Infarction

Background: Although serum paraoxonase-1 (PON-1) and arylesterase (ARE) activities are linked to the presence of stable coronary arterial disease, their correlation with SYNTAX Score I (SS1) and SYNTAX Score II (SS2) has not been known well. Our aim was to determine the association between PON-1 and ARE activities, together with the genetic polymorphism of PON-1, and both SS1 and SS2 in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: Consecutive patients with acute STEMI (n=102: 78 male, 24 female; mean age=61.14±12.25 y) admitted to the Emergency Department of Kırşehir Ahi Evran University Hospital between August 2018 and December 2018 were enrolled. PON-1 and ARE activities were determined on hospital admission. The SS1 and SS2 scores were calculated by using the angiographic and clinical data. Subsequently, the relationships between the activities of the enzymes, together with the genetic polymorphism of PON-1, and both SS1 and SS2 were interrogated. Results: The mean SS1 and the mean SS2 were 19.8±9.7 and 32.3±11.5, respectively. The phenotype distributions of PON-1 were Q192Q (n=60), R192Q (n=35), and R192R (n=7). The respective PON-1 (U/L) and ARE (kU/L) activities were 514.85±29.34 and 216.82±36.72 in the low SS1 category; 527.60±56.31 and 203.95±55.97 in the intermediate SS1 category; and, 690.10±11.07 and 238.48±45.65 in the high SS1 category.PON-1 and ARE activities did not correlate with the SS1 categories, and varying SS2 scores. The distribution of the Q192R polymorphism was homogenous among the different SS1 and SS2 scores. The localization of acute STEMI also did not associate with the activities of either enzyme. Conclusion: Admission serum PON-1 and ARE activities, together with the PON-1 Q192R genetic polymorphism, showed association neither with SS1 and SS2 nor with the localization of infarction in our acute STEMI patients.

Effects of Securigera securidaca (L.) Degen & Dorfl seed extract combined with glibenclamide on paraoxonase1 activity, lipid profile and peroxidation, and cardiovascular risk indices in diabetic rats.

Introduction: Seeds of Securigera securidaca (L.) Degen & Dorfl are rich in flavonoids and phenolic acids which have potent biological effects. The current study was undertaken to evaluate the effects of hydroalcoholic extract of S. securidaca seeds (HESS) alone, and in combination with a standard drug, glibenclamide (GB) on paraoxonase1 (PON1) activity, lipid profile and peroxidation, and cardiovascular risk indices in streptozotocin (STZ) induced diabetic rats. Methods: Forty-eight male Wistar rats were randomly divided into eight equal groups and orally treated with various doses of HESS (100, 200, 400 mg/kg) alone and in combination with GB (5 mg/kg) for 35 consecutive days. After blood sampling, lipid profile including triglyceride (TG), cholesterol, high, low and very low-density lipoprotein-cholesterol (HDL-C, LDL-C, and VLDL-C), as well as serum PON1 activity, were assessed. Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) levels were also measured. Several indices of cardiovascular risk and the correlation between PON1 activity and these indices were calculated based on the obtained results from the lipid profile. Results: Induction of diabetes could dramatically alter all of the parameters mentioned above, and the lower dose of HESS (100 mg/kg) was not effective in restoring the parameters. However, the higher doses (200 and 400 mg/kg) alone and in combination with GB could significantly improve lipid profile, restore PON1 activity, and decrease cardiovascular risk indices, MDA, as well. However, neither HESS nor GB could significantly reduce TNF-α and hs-CRP. A significant negative correlation also was detected between PON1 activity and cardiovascular risk indices. Conclusion: conclusively, HESS can be considered as a potent antihyperlipidemic agent with remarkable cardioprotective effects and can potentiate the antidiabetic effects of GB.

Selected Abstracts Presented at the Annual Conference of the Canadian Society of Clinical Chemists (CSCC), Saint John, NB, 2-5 June 2019

Low serum PON1 activities (paraoxon, phenyl-acetate or lactone substrates) are associated with coronary heart disease (CHD). We investigated the rate of diazoxon hydrolysis by PON1 in a population with CHD.Case- control study of 410 subjects with CHD and 274 controls. PON1 activity towards paraoxon and diazoxon, PON1 serum concentration and the PON1–55 and 192 polymorphisms were determined.There were no differences in the distribution of the PON1–55 or PON1–192 genotypes between the CHD and controls, however, PON1 activity towards diazoxon (DIAZ) was significantly (+160%) higher in CHD. In the control population, DIAZ was significantly different between the PON1–192 genotypes in the order QQ > QR > RR (P < .001). However, in CHD the order was QQ > QR = RR. In CHD DIAZ was significantly higher in all the PON1–192 and 55 genotypes compared to controls. In both populations DIAZ was significantly different between the PON1–55 genotypes in the order LL > LM > MM (P < .001).If this result can be replicated in other studies and/or with other PON1 substrates, there may be major diagnostic and mechanistic implications for the relationship of PON1 and CHD.

FRIED FOOD AND POSSIBLE HEALTH HAZARDS

FRIED FOOD AND POSSIBLE HEALTH HAZARDS

Serum NOX-2 concentrations and paraoxanase-1 activity in subclinical hypothyroidism: a pilot study

Abstract Objective Subclinical hypothyroidism (SH) is one of the most prevalent endocrine disorders. Although recent data suggest an imbalanced oxidative status in SH, the mechanisms of increased oxidative stress are poorly figured out. The primary goal of this research was to analyze potential sources of ROS and the relationship between serum NOX-2 levels and paraoxonase-1 (PON-1) activity in SH. Serum lipid changes in SH patients which had been determined were compared to healthy control group. Materials and methods Thirty-one patients diagnosed with SH and 30 healthy controls were included in the study. The quantitative sandwich ELISA was used for the detection of serum NOX-2 levels. Spectrophotometric method was used to determine serum PON-1 activity. Results Higher median serum NOX-2 levels were determined in patients than in the control group (p = 0.004). Lower median serum PON-1 activity was determined in patients as to aforementioned control group (p &lt; 0.0001). As a consequence, no statistically remarkable correlation was identified between PON-1 activity and NOX-2 levels. Triglyceride (TG) concentrations were determined as superior in patients to control group (p &lt; 0.0001). Conclusion Over-production of NOX-2 and decreased PON-1 activity contribute to the increased oxidative stress in SH patients. Larger prospective studies required to confirm these findings.

PON1 lactonase activity and its association with cardiovascular disease

BackgroundParaoxonase 1 (PON1) is important in the development of atherosclerosis, and it has become the subject of intensive research. Our aim was to evaluate the association of serum PON1 activity and polymorphisms with cardiovascular disease (CVD) using four different substrates. Materials and methodsActivity of PON1-related to arylesterase (AREase and 4-CMPAse), paraoxonase (PONase), and lactonase (LACase), and polymorphisms (A-162G, T-108C, L55M, and Q192R) were evaluated in subjects with CVD, cardiovascular risk factor (CFR), and controls. An ordered logistic-regression analysis of PON1 phenotypes was performed in the CVD group with respect to the control group. Results and conclusionsLogistic-regression analysis showed that CC-108 genotype was associated with CRF and CVD. The CVD group had the lowest activities of PON1. The LACase might be a better biomarker for CVD (OR, 0.52; 95% CI, 0.44–0.61) followed by CMPAse (OR, 0.82; 95% CI, 0.77–0.86), AREase (OR, 0.98; 95% CI, 0.97–0.99) and PONase (OR, 0.99, 95% CI, 0.99–0.99). Logistic regression of PON1 phenotypes by haplotypes showed that LACase activity was not influenced by the polymorphisms and that it could be a new potential biomarker in the development of CVD. Larger scale longitudinal studies are required.

Low Serum Paraoxonase-1 Activity Associates with Incident Cardiovascular Disease Risk in Subjects with Concurrently High Levels of High-Density Lipoprotein Cholesterol and C-Reactive Protein.

Paroxonase-1 (PON1) is a key enzyme that inhibits low-density lipoprotein oxidation and consequently atherogenesis. Here, we assessed whether low serum PON1 activity associates with incident cardiovascular disease (CVD) in subjects with high levels of high-density cholesterol (HDL-C) and C-reactive protein (CRP), a marker of low-grade systemic inflammation. Cox proportional-hazards modeling of incident CVD risk (11 years mean follow-up) adjusted for relevant clinical and biomarker covariates was performed on a population-based study (N = 7766) stratified into three groups: low CRP—(LR; event rate 4.9%); low HDL-C/high CRP—(HR1; event rate 14.4%); and high HDL-C/high CRP—(HR2; event rate 7.6%). Modeling results for PON1 activity in HR2 were significant and robust (hazard ratio/SD unit—0.68, 95% CI 0.55–0.83, p = 0.0003), but not so for LR and HR1. Analyses in HR2 of the interaction of PON1 with HDL-C, apoA-I, apoA-II, and apoE levels were significant only for PON1 with apoE (hazard ratio—1.77, 95% CI 1.29–2.41, p = 0.0003). Subsequent subgroup analysis revealed inverse risk dependence for apoE at low PON1 levels. In conclusion, in a population-based study of subjects with concurrently high HDL-C and CRP levels, low serum PON1 activity associates with incident CVD risk with risk accentuated at low apoE levels.

Assessment of PON1 activity and circulating TF levels in relation to BMI, testosterone, HOMA-IR, HDL-C, LDL-C, CHO, SOD activity and TAC in women with PCOS: An observational study

BackgroundPolycystic Ovary Syndrome (PCOS) is the most common female endocrinopathy among premenopausal women associated with hyperandrogenism, obesity, dyslipidemia, insulin resistance and inflammation. Oxidative stress is an important component of cardio-metabolic risk seen in PCOS. Material and methodsA total of 95 women with PCOS and 95 healthy controls were included in this observational study. Serum PON1 activity and stress markers were measured by spectrophotometric methods. Circulating TF level was measured by ELISA. ResultsWe found decreased PON1 activity and increased TF levels in women with PCOS compared to healthy controls. Fasting insulin, HOMA-IR, testosterone, LDL-C, MDA, PC and SOD activity were significantly increased whereas FGIR, QUICKI, HDLC, CAT and TAC were significantly decreased in PCOS women than controls. We observed a positive association of PON1 activity with FGIR, QUICKI, HDL-C and TAC, and its negative association was observed with LH, testosterone, fasting insulin and HOMA-IR in PCOS women. We further observed a positive association of TF with waist, waist to hip ratio, BMI, glucose 1hr, cholesterol, LDL-C, SGPT, uric acid and SOD activity in PCOS women. ConclusionsDecreased PON1 activity and raised circulating TF levels are respective indicators of pro-inflammatory and procoagulant status in PCOS women. The imbalanced oxidant/antioxidant status further supports the evidences that PCOS is an oxidant state. Further, the association of PON1 activity and TF levels with the clinical, laboratory findings and stress marker levels suggest that these factors taken together are involved in aggravating the pro-inflammatory status in PCOS women.

Organophosphate Pesticide Exposure Reduced Serum Paraoxonase1 (PON1) Activity Which Correlated With Oxidative Stress in Pesticide Factory Workers

Organophosphate Pesticide Exposure Reduced Serum Paraoxonase1 (PON1) Activity Which Correlated With Oxidative Stress in Pesticide Factory Workers

Serum Paraoxonase-1-Related Variables and Lipoprotein Profile in Patients with Lung or Head and Neck Cancer: Effect of Radiotherapy.

We investigated alterations in the levels of the antioxidant paraoxonase-1 (PON1) and the lipoprotein profile (analyzed by nuclear magnetic resonance) in patients with lung cancer (LC) or head and neck cancer (HNC), and the effects produced thereon by radiotherapy (RT). We included 33 patients with LC and 28 patients with HNC. Before irradiation, and one month after completion of RT, blood samples were obtained. The control group was composed of 50 healthy subjects. Patients had significantly lower serum PON1 activity and concentration before RT than the control group. PON1-related variables were good predictors of the presence of LC or HNC, with analytical sensitivities and specificities greater than 80%. Patients showed a significant increase in the number of particles of all subclasses of very-low-density lipoproteins (large, medium and small). However, these changes were not maintained when adjusted for age, sex, and other clinical and demographic variables. Irradiation was associated with a significant increase in PON1 concentration and, only in patients with HNC, with an increase in high-density lipoprotein-cholesterol concentration. Our results suggest that determinations of the levels of PON1-related variables may constitute good biomarkers for the evaluation of these diseases. Studies with a larger number of patients are needed to fully confirm this hypothesis.

Citicoline Ameliorates Neuro- and Genotoxicity Induced by Acute Malathion Intoxication in Rats

Objective: In the present study, we explored the therapeutic potential of citicoline in preventing malathion induced neurotoxicity and genotoxicity. Citicoline has been shown to act as a neuroprotective in experimental animal models of ischemia and other types of brain injuries. Methods: Acute malathion intoxication was induced by intraperitoneal injection of malathion (150 mg/Kg, once per day) for two successive days. Citicoline was co-administered in three doses (100, 200, 300 mg/kg, p.o.). Serum Butyrylcholine esterase (BChE) and Paraoxonase-1 (PON-1) were assessed as exposure biomarkers. Oxidative stress biomarkers were assessed in the different brain regions (cortex, striatum, and subcortex) in addition to TNF-α. Genotoxicity was tested by chromosomal aberrations, mitotic index, DNA fragmentation, and micronucleus tests. Results: Malathion administration resulted in marked suppression of serum BChE and PON-1 activities. Also, the exposure to the pesticide led to elevated malondialdehyde (MDA), nitric oxide (NO), and decreased reduced glutathione (GSH) levels in investigated brain regions in addition to elevated striatal tumor necrosis factor-α (TNF-α) level. Malathion also caused profound structural chromosomal aberrations, increased liver DNA fragmentation, and mitotic index. These effects were alleviated with the administration of citicoline dose-dependently. Conclusion: Our data indicate that citicoline can protect against malathion neurotoxic and genotoxic potential, possibly through antioxidant, anti-inflammatory activities, and restoring energy stores

Serum Paraoxonase-1 (PON1) Activity and Concentration: A new biomarker in Egyptian Patients with Liver Cirrhosis and Hepatocellular Carcinoma

Background and study aim: Hepatoma is the most common cancer worldwide, being regarded as the fifth of all malignancies. Mandating for a new, sensitive and specific markers for HCC are critically needed. Human paraoxonase-1 (PON-1), a Ca+2 dependent esterase in the liver, with antioxidant functions, and binds to the HDL particles and hence discarding carcinogenic lipid radicals as byproduct of lipid peroxidation. The aim of this study was to estimate the importance of serum PON-1 activity and concentration in HCC in Egyptian patients as a more sensitive and specific biomarker compared to an established biomarker; Alpha-fetoprotein (AFP). Patients and Methods: This study was conducted on 88 subjects: 64 patients; 40 patients with HCC, 24 cirrhotic patients and 24 healthy subjects who admitted in Internal Medicine Department, Suez CanalUniversityHospital, Ismailia, Egypt. Clinical and radiological investigations in those of the Cirrhotic, and HCC groups for viral hepatitis markers, liver function tests, serum assay of AFP and PON-1 activity and cconcentrations. Results: The results showed that PON-1 concentration was found significantly lower in HCC patients than those of the control and Cirrhotic group (p<0.001).The sensitivity and specificity of PON-1 concentration for HCC were superior to those of AFP and PON-1 activity especially in recently detected HCC. PON-1 concentration had a sensitivity of 88.3% and specificity of 90.48% at the optimal cut-off value of 70.55 (ng/ml). AFP gives a sensitivity of 82.50% and specificity of 73.08 at a cut-off 20.44 ng/ml. Conclusion: This study demonstrates that PON1 concentration and activity were superior to AFP in the recently detected HCC.

Serum Paraoxonase 1 Activity in Patients with Organophosphate Poisoning: A Potential Indicator of Prognosis

Background: Human serum paraoxonase 1 (PON1) hydrolyzes organophosphate (OP) compounds and so significantly alters an individual’s susceptibility to the toxicity of these chemicals. The study was designed to assess the serum PON1 activity in a series of patients with OP poisoning. Methods: Suspected OP poisoning patients presented within 6 hours of consumption at emergency department were recruited. Demographic information of patients, clinical findings, treatments given, complications, length of hospital stay and clinical outcome were collected into datasheets. Patients were graded into moderate and severe poisoning. Serum PON1 was measured by ELISA method and serum cholinesterase by butyrylthiocholine method. Results: Mean serum PON1 level in patients with severe poisoning was significantly lower than those with moderate poisoning (426 ± 179 U/L vs. 868 ± 79 U/L, P < 0.001). Serum PON1 significantly correlated with serum cholinesterase levels (r = 0.400, P < 0.001) and negatively associated with total length of hospital stay (r = -0.338, P < 0.001), total atropine dose (r = -0.826, P < 0.001), serum amylase (r = -0.331, P < 0.001), lipase (r = 0.260, P = 0.011) and total creatinine kinase (r = -0.456, P < 0.001). Serum PON1 and cholinesterase levels were significantly lower in expired patients and those who required ventilation assistance as compared to recovered patients who did not require ventilation assistance. Conclusion: Lower PON1 activity was significantly associated with lower serum cholinesterase and poorer outcomes. PON1 activity may be considered as an indicator of prognosis in OP poisoning.

Intrafollicular paraoxonase 1 activity and the steroidogenic potential of the first post-partum dominant follicle in dairy cows.

Cows experiencing high levels of inflammation and specific metabolic conditions tend to have slower follicular growth and lower serum and follicular concentrations of oestradiol (E2). Paraoxonase1 (PON1) activity decreases during inflammatory processes. Therefore, the aim of this study was to evaluate the association between serum and intrafollicular (FF) PON1 activity and the serum and intrafollicular levels of E2 and progesterone (P4), as well as the mRNA expression of genes related to steroidogenesis, metabolism and inflammation in the first post-partum dominant follicle of Holstein cows. No correlation was found between PON1 activity, the expression of the analysed genes and levels of follicular E2 and P4, except for a negative correlation between serum E2 and follicular PO1 activity. Also, no correlation was found between serum and follicular PON1 during the first post-partum follicular wave.

Influence of Surgical Procedures on Serum Paraoxonase-1-Related Variables and Markers of Inflammation in Hospitalized Patients

Purpose: Surgical stress is a phenomenon not completely understood from the biochemical point of view, although it produces alterations in the oxidative balance and inflammatory status. The present study aimed to investigate the alterations of the circulating levels of paraoxonase-1 (PON1)-related variables and markers of inflammation in hospitalized patients who underwent surgery. Methods: We recruited 285 hospitalized patients. Of those, 115 were hospitalized due to a surgical intervention and 170 for reasons other than surgery. The control group consisted of 128 healthy volunteers. A blood sample was obtained for the measurement of serum PON1-related variables, and C-reactive protein (CRP), chemokine (C-C motif) ligand 2 (CCL2), and procalcitonin concentrations. Results: Hospitalized patients had lower serum PON1 activities [paraoxonase: 215.6 (168.6 – 277.8) vs. 298.7 (229.7 – 382.6) U/L, p < 0.001; lactonase: 3.0 (2.3 – 3.7) vs. 5.7 (4.6 – 6.5) U/L, p < 0.001], and higher CCL2, CRP and procalcitonin concentrations than the healthy individuals. The days elapsed following surgery and the duration of the procedure itself inversely correlated with PON1-related variables, and directly correlated with CRP concentrations. Patients that were operated on by laparotomy had higher PON1 activity than patients operated on by laparoscopy. Local and regional anesthesia was associated with higher PON1 activities and lower CRP concentrations. Conclusion: These results show a decrease in PON1 activities and an increase in acute phase response in hospitalized patients undergoing surgery and support the hypothesis that these phenomena are related to post-surgical metabolic alterations.

Paraoxonase 1 Activity, Polymorphism and Atherosclerosis Risk Factors in Patients Undergoing Coronary Artery Surgery.

Background: Paraoxonase1 (PON1), an enzyme connected to high density lipoproteins (HDL) particles, plays an important role in protecting arteries against atherosclerosis. The serum activity and concentration of PON1 depends on several genetic polymorphisms as well as environmental factors. Materials and methods: Investigated population consisted of 71 patients aged 43–76 years with confirmed coronary heart disease (CHD). Established risk factors of CHD such as hypertension, elevated total cholesterol and LDL cholesterol (LDL-C), low HDL cholesterol (HDL-C), diabetes mellitus, obesity, smoking and premature CHD in family history were assessed. PON1 genotype for −108C/T promotor region was determined by polymerase chain reaction-restriction fragments length polymorphism (PCR–RFLP) method. Paraoxonase activity towards paraoxon and arylesterase activity towards phenyl acetate were measured spectrophotometrically. Results: Significant correlations between diabetes mellitus and paraoxonase activity (R = −0.264, p = 0.026) and between the premature coronary heart disease in family history and PON1 activity (R = −0.293, p = 0.013) were found. In multivariate analysis, PON1 paraoxonase activity was independently of confounding factors associated with diabetes (OR = 0.985; p = 0.024) and premature CHD in family history (OR = 0.983; p = 0.027). PON1 activity towards aryl acetate positively correlated with HDL-C level (R = 0.255, p = 0.032). In patients treated with statins, PON1 paraoxonase activity was significantly (p = 0.033) higher than in patients without treatment. Conclusions: In diabetic patients with CHD, paraoxonase activity is lower than in normoglycemic patients despite similar lipid profiles. Diabetes and positive family history in patients with overt CHD are associated with the serum PON1 activity, which might be an additional factor helpful in evaluating cardiovascular risk in this group of patients.