Serum Arylesterase Research Articles

PON1 and PON3 in Alzheimer's Disease: Similar Functions but Different Roles.

Paraoxonase 1 (PON1) and Paraoxonase 3 (PON3) are enzymes located on the surface of high-density lipoprotein (HDL) and share similar antioxidant properties, possibly modulated by other proteins such as Myeloperoxidase (MPO), which drives the shift from functional to dysfunctional HDL. PON1 has been extensively studied in relation to Alzheimer's Disease (AD), but the role of PON3 remains unknown. To fill this knowledge gap, the study analyzed PON3 protein levels and PON1-arylesterase activity in 99 AD patients, 100 patients with mild cognitive impairment (MCI), and 79 cognitively normal controls. The results showed that serum PON3 levels remained unchanged across all groups. In contrast, serum arylesterase activity was significantly reduced in both AD and MCI patients compared to controls (p < 0.001 for both comparisons). Surprisingly, there was no correlation between arylesterase activity and MPO protein concentration or activity. However, PON3 was found to have a significant positive correlation with both MPO concentration (r = 0.507, p < 0.0001) and MPO activity (r = 0.264, p < 0.01). In conclusion, we demonstrated for the first time that PON1 and PON3 have distinct relationships with AD, with only PON1 showing a decrease in activity in this disease, while PON3 levels remained unchanged. Another noteworthy finding was the selective correlation between PON3 and MPO, which may suggest a preferential physical association of PON3 with dysfunctional HDL.

Serum Paraoxonase Activity and Phenotype Distribution in Covid-19 Patients

Objective: For the phenotype classification, it is important to determine the relationship between enzyme activity and the severity of the COVID-19 disease. Reaching significant differences between healthy and infected individuals in terms of genotype and allele distributions may be a guide in the fight against the COVID-19 pandemic. This study, it was aimed to investigate the relationship between serum arylesterase PON1 enzyme activity and disease severity in COVID-19 patients. Methods: Patients over the age of 18 who applied to the Emergency Service between 01-30 April 2020 and were examined with a preliminary diagnosis of COVID-19 were included in the study. In the study, serum PON1 activity was measured in the venous blood of 56 patients diagnosed with Covid-19 disease by either CT or RT-PCR and who have not received any systemic treatment yet. Results: The Arylesterase (AREase) and Paraoxonase (POase) activity levels of the study and control groups were 131.49 ± 52.75 kU/L 142.29 ± 38.82 kU/L, 276.48 ± 220.4 U/L 505.30 ± 301.4 U/L, respectively. It was found that 64.3 % of those infected with Covid-19 had the low-activity PON1 phenotype (p= 0.007) Conclusion: Genetic variability in PON1 may be associated with exposure to or risk of developing the disease. As a result, vaccination of individuals with low activity phenotype can be given priority at the vaccination stage in order to reduce the mortality rate in the fight against the pandemic. Awareness and protection measures of societies with low activity phenotypes can be increased.

Investigation of the effects of Terminalia chebula seed hydroalcoholic extract on Paraoxonase1 enzyme activity in rats

Background and aims: Paraoxonase 1 (PON1) is related to high-density lipoprotein (HDL) in serum and protects against low-density lipoprotein (LDL) oxidation. This study aimed to investigate the effects of Terminalia chebula on PON1 in hyperlipidemic rats and the molecular docking effects of some compounds of this medical plant on PON1 activity. Methods: Overall, 40 male rats (200–250 gr) were randomly divided into four groups, including the control group, the hyperlipid group, the hyperlipid group receiving 400 mg/kg of the hydroalcoholic extract of T. chebula seeds, and the hyperlipid group receiving 800 mg/kg of the hydroalcoholic extract of T. chebula seeds. The PON1 arylesterase activity in serum and the PON1 gene expression in the liver tissue underwent investigation. Then, the molecular docking effects of its compounds were studied on PON1 through in-silico studies using the AutoDock software (version 4.2.0). Results: T. chebula decreased (P&lt;0.001) the serum triglycerides from 105.88±10.15 mg/dL in the hyperlipidemic group to 66.88±14.90 and 74.25±9.51 mg/dL in hyperlipidemic groups receiving 400 and 800 mg/kg of the hydroalcoholic extract of T. chebula seeds, respectively. In addition, the PON1 serum aryl esterase activity increased from 202.12±6058 in hyperlipidemic rats to 224.34±58.74 (P=0.83) and 235.80±37.05 (P=0.6) in hyperlipidemic groups receiving 400 mg/kg and 800 mg/kg of the hydroalcoholic extract of T. chebula seeds, respectively. It also demonstrated a significant effect on PON1 gene expression (P&lt;0.001). In addition, the in-silico and docking results revealed that the main antioxidant compounds of T. chebula, such as catechin, kaempferol, and quercetin, could bind to the PON1 enzyme directly and influence the enzyme activity. Conclusion: T. chebula increased PON1 activity and PON1 gene expression. However, among the plant’s compounds, catechin, kaempferol, and quercetin played the most substantial role in the PON1 activity. It seems that these compounds can be useful as co-treatments in hyperlipidemia therapies.

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.

Expression of paraoxonase 1 in HEK293 cells and its effect on lactonase and arylesterase activity in samples containing human serum and/or prooxidant or antioxidant agents - a preliminary study

Expression of recombinant paraoxonase 1 (PON1) in the human embryonic kidney (HEK293F) cell line was evaluated. Two recombinant human PON1 proteins were investigated: PON1-Fc, which has an Fc-tag on its C-terminal, and His-PON1-Fc, which has an Fc-tag on its C-terminal and histidine on its N-terminal. The influence of high and low-density lipoproteins, copper ions, iron ions, and thiolactone homocysteine, on arylesterase and lactonase activities of PON1 in human serum was examined. Two activities of PON1, arylesterase and lactonase, were measured using earlier elaborated kinetic spectrophotometric method with temperature control at 37°C using the water thermostated cuvette holder. It was demonstrated that the HEK293F expression platform is useful for obtaining recombinant human PON1 protein. Also, addition of high-density lipoprotein increased serum arylesterase and lactonase activity of PON1 to a greater extent than the addition of PON1-Fc or HisPON1-Fc recombinant proteins. In contrast, the addition of high-density lipoprotein to samples containing PON1-Fc or His-PON1-Fc did not increase PON1 activities, while low-density lipoprotein, copper ions, and iron ions, depressed PON1 arylesterase and lactonase activity. Obtained results indicated that it may be advantageous to stimulate PON1 activities rather than supplement with endogenous PON1 protein and HDL, which could be an interesting direction for further study. Furthermore, the work has highlighted some potential research directions for the use of PON1 as a therapeutic molecules. Nevertheless, the study had some limitations and should therefore be treated as a preliminary study.

Paraoxonase 1 rs662 polymorphism, its related variables, and COVID-19 intensity: Considering gender and post-COVID complications.

In this study, we aimed to investigate the effect of paraoxonase 1 (PON1) rs662 polymorphism, arylesterase (ARE) activity, and the serum lipid profile in patients with coronavirus disease 2019 (COVID-19) in different stages of the disease considering post-COVID outcomes. A total of 470 COVID-19 patients (235 female and 235 male patients) were recruited into the study, and based on the World Health Organization (WHO) criteria, the patients were divided into three groups: moderate, severe, and critical. PON1 rs662 polymorphism was determined by the Alw 1 enzyme followed by agarose gel electrophoresis. Moreover, serum levels of triglycerides (TG), cholesterol (Chol), high-density lipoprotein-cholesterol (HDL-c), and low-density lipoprotein-cholesterol (LDL-c), as well as the level of the ARE activity of PON1 in the sera of patients were measured at the time of infection and one and three months after hospitalization. There was a significant relationship between the G allele and the severity of the disease. In addition, the probability of death in homozygous individuals (GG) was higher than in heterozygous patients (GA), and it was higher in heterozygous patients than in wild-type individuals (AA). There was also a significant relationship between the decrease in serum lipids and the intensity of COVID-19. On the contrary, at the onset of the disease, the HDL-c level and serum ARE activity were reduced compared to one and three months after COVID-19 infection. The findings of this study indicated the significant impact of PON1 rs662 polymorphism on ARE activity, lipid profiles, disease severity, and mortality in COVID-19 patients.

Alteration in serum oxidative stress balance in patients with different circulating high-density lipoprotein cholesterol levels

Introduction and ObjectivesHigh-density lipoprotein cholesterol (HDL-C) is known to be a key player in reverse cholesterol transport and this function is associated with its atheroprotective role. Low HDL-C is a strong independent risk factor for cardiovascular disease, premature atherosclerosis and increased oxidative stress. However, the clinical benefit of high HDL-C through diet or drug therapy is still controversial. MethodsThis study included 50 patients with isolated low HDL-C (≤35 mg/dl), 52 patients with isolated high HDL-C (≥70 mg/dl), and 33 age- and gender-matched controls with normal HDL-C. ‘Isolated’ was defined as excluding all clinical conditions associated with increased oxidative stress and inflammation, which may affect the structural state of HDL-C. In addition to arylesterase (ARES) activity and plasma thiol levels, laboratory parameters associated with oxidative stress were also assessed. ResultsLevels of ARES (758 [169-1150] vs. 945 [480-1215] and 821 U/l [266-1220]; p<0.01) and total thiols (233±41 vs. 259±46 μmol/l; p=0.02) were markedly higher in patients with high HDL-C. More importantly, total antioxidant capacity, oxidative stress index, creatine and serum ARES levels were associated with changes in serum HDL-C levels. ConclusionIn patients with isolated high HDL-C, we determined that while serum ARES activity and plasma thiol concentrations were significantly higher, the other markers associated with oxidative stress decreased markedly. Additionally, the present study demonstrated that serum oxidative stress status is very important to maintain the positive effects of HDL-C.

Usefulness of the Measurement of Serum Paraoxonase-1 Arylesterase Activity in the Diagnoses of COVID-19.

The development of inexpensive, fast, and reliable screening tests for COVID-19 is, as yet, an unmet need. The present study was aimed at evaluating the usefulness of serum arylesterase activity of paraoxonase-1 (PON1) measurement as a screening test in patients with different severity levels of COVID-19 infection. We included 615 COVID-19-positive patients who were classified as asymptomatic, mildly symptomatic, severely symptomatic, or fatally symptomatic. Results were compared with 50 healthy volunteers, 330 patients with cancer, and 343 with morbid obesity. Results showed PON1 activity greatly decreased in COVID-19 compared to healthy volunteers; a receiver operating characteristics plot showed a high diagnostic accuracy. The degree of COVID-19 severity did not influence PON1 levels. Our results indicated that PON1 determination was efficient for disease diagnosis, but not for prognosis. Furthermore, patients with obesity or cancer presented alterations similar to those of COVID-19 patients. As such, elevated levels of PON1 indicate the absence of COVID-19, but low levels may be present in various other chronic diseases. The assay is fast and inexpensive. We suggest that PON1 measurement could be used as an initial, high cut-off point screening method, while lower values should be confirmed with the more expensive nucleic acid amplification test.

Impact of anthocyanin on genetic stability in mammary adenocarcinoma-induced mice treated with methotrexate.

BackgroundGenetic instability leads to genome mutations, changes in nucleotide sequences, rearrangements, and gains or losses of part of the chromosomes. This instability can initiate and develop cancer. This study evaluated genomic stability in methotrexate and anthocyanin-treated mammary adenocarcinoma model. Seventy albino mice were divided into seven groups: negative control, anthocyanin, methotrexate, Ehrlich’s solid tumor; Ehrlich’s solid tumor and methotrexate; Ehrlich’s solid tumor and anthocyanin; and Ehrlich’s solid tumor, methotrexate, and anthocyanin groups.ResultsTumor weight and size were evaluated. Serum arylesterase activity was low in all the induced tumors and those treated with anthocyanin, methotrexate, or both. Poly[adenosine diphosphate (ADP)-ribose] polymerase activity was high, and glutathione S-transferase activity was low in the tumors treated with anthocyanin, methotrexate, or both, compared with that of the untreated tumor. There was an increase in DNA damage in the mice with solid tumors and those injected with methotrexate or methotrexate and anthocyanin, compared with that in the untreated mice.ConclusionsThere was a decrease in genetic instability and DNA damage in the tumor-bearing mice treated with anthocyanin, with a concomitant increase in nuclear poly[adenosine diphosphate (ADP)-ribose] polymerase activity, compared with those of the untreated group. Anthocyanin exerted positive effects in the treatment of mammary adenocarcinoma.

Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders.

Organophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene PON1 located on human chr. 7q21.3. In autism spectrum disorder (ASD) and in attention-deficit/hyperactivity disorder (ADHD), a correlation between OP exposure and disease onset has been reported. In this case-control study, we aimed to replicate our previous work showing reduced levels of serum PON1 arylesterase activity in Italian and Caucasian-American ASD samples, and to extend our analysis to other neurodevelopmental disorders, namely ADHD and developmental language disorder (DLD), also known as specific language impairment (SLI). The arylesterase activity, measured using standard spectrophotometric methods, is significantly reduced in the ADHD, and not in the ASD sample compared with the controls. Our previous results seemingly stem from spuriously high arylesterase levels in the former control sample. Finally, genotyping SNPs rs705379 and rs662 using TDI-FP, a significant effect of rs705379 alleles on the serum arylesterase activity is observed in all of the subgroups tested, regardless of diagnosis, as well as a lack of association between PON1 gene polymorphisms and ASD/ADHD susceptibility in the Italian population. In summary, the serum arylesterase activity is reduced in children and adolescents with ADHD, and this reduction is not due to the functional PON1 gene variants assessed in this study. Based on previous literature, it may more likely reflect enhanced oxidative stress than specific genetic underpinnings.

Evaluation of serum analytes in pregnant and non-pregnant dairy cows as indicators of pregnancy

This study was conducted to reveal the dynamics of haematological indicators in pregnant and non-pregnant dairy cows. Sixty multiparous healthy dairy cows were divided into four groups based on the length of time they had been pregnant, namely first, second and third trimesters, and non-pregnant (n=15 each). Blood was collected from each animal, and serum was harvested and stored at -20 °C for biochemical profiling. Concentrations of serum total oxidants (TOC), ceruloplasmin oxidase (CpO) and triiodothyronine (T3) were higher (P &lt;0.05) during the third trimester compared with non-pregnant cows. Serum arylesterase (Ary) concentration was lower (P &lt;0.05) during the second and the third trimesters compared with the non-pregnant cows. The concentration of serum total homocysteine (tHcy) was higher (P &lt;0.05) the third trimester compared with the first and the second trimesters. The concentrations of serum total antioxidants (TAC), paraoxonase 1 (PON1), thyroxine (T4), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were not different in the pregnant and the non-pregnant cows. Thus, TOC, Ary, CpO, tHcy and T3 could be taken as biological markers to assess the progression of pregnancy and to develop management tools to improve health status during late gestation in dairy cows&#x0D; Keywords: ceruloplasmin, hepatic enzymes, late gestation, triiodothyronine

The Effects of Chronic Low Dose Exposure of Chlorpyrifos on the Rat Kidney

Introduction: An increased incidence of chronic kidney disease (CKD) was reported among agricultural workers who were exposed to organophosphates (OP). There is little information on the effects of chronic low OP exposure on kidney in experimental animals. Chlorpyrifos (CPF) is a common type of OP used in agriculture. Thus, the aim of this study was to assess the effects of chronic low subcutaneous exposure of CPF on the kidney. Methods. Eighteen male Sprague Dawley rats were divided into three groups, with six rats in each group. Group 1 served as a control group, and groups 2 and 3 received a subcutaneous vehicle (3% dimethyl sulfoxide + 97% v/v soy oil) or CPF (18.0 mg/kg) respectively, every other day for 180 days. Serum urea, creatinine, uric acid, cystatin C, electrolyte levels, acetylcholinesterase (AChE), and arylesterase (ArE) activities were measured. Histopathological changes in the kidney tissues were examined. Results. Urea, creatinine, uric acid, and cystatin C levels were significantly increased (p &lt; 0.05), while electrolytes were reduced (p &lt; 0.05) in the CPF-treated rats. Both AChE and ArE activities were depressed in the CPF group (p &lt; 0.01 and p &lt; 0.001, respectively). Diffuse necrosis of proximal tubules and glomerular hypercellularity were observed in the kidney in the CPF group. Conclusion. A chronic low dose of CPF via subcutaneous exposure caused considerable renal tubular necrosis and derangement of glomerular function. These findings suggest that chronic occupational OPs exposure can cause kidney damage.

Investigation of anti-inflammatory effects of bee venom in experimentally induced adjuvant arthritis.

ObjectivesRheumatoid arthritis is a multisystemic inflammatory disease characterized by destruction of the joints. An effective treatment method of the disease has not been developed yet. The aim of the present study is to evaluate the effects of bee (Apis mellifera anatoliaca) venom (BV) on serum inflammatory parameters, serum antioxidant load and clinical parameters of experimentally induced adjuvant arthritis in rats.Material and methodsA total of 35 Wistar albino male rats were used. The animals were divided into 5 groups. First group animals served as negative controls. The second, third, fourth and fifth groups were used for experimental arthritis induction. Following clinical development of arthritis, the first group was subcutaneously administered 0.2 ml of physiological saline, and the second, third and fourth groups were treated subcutaneously with 2 µg/kg, 4 µg/kg and 20 µg/kg once a week three times. Physiological saline injected fifth group animals were used as a sham-treatment group. Clinical observations and evaluation of arthritis were made at the 15th day, and at the end of the experiment. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, paraoxonase, serum aryl esterase, high-sensitivity C reactive protein, interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) were determined in cardiac blood samples taken at the end of the 29th day.ResultsFrom the data, total oxidant level (TOL) and oxidative stress index (OSI) were calculated. Significant improvements were observed in the clinical signs of arthritis and inflammatory markers such as in IL-1β, TNF-α, IL-6 and TOL and OSI in the 20.0 µg/kg BV-administered group. Bee venom administration did not cause any significant increase in ALT and AST values or signs of liver toxicity.ConclusionsBee venom treatment was effective in alleviation of symptoms of the experimental rat adjuvant arthritis by means of clinical observation and serum inflammatory markers.

Paraoxonase-1 Enzyme Activity and Oxidative Status in Pulmonary Hypertension Original Article

Objective: Oxidative stress has been considered to be one of the main causes for the development of pulmonary hypertension (PH) via leading alteration of pulmonary vasomotor tone induced by hypoxia. The aim of this study is to determine the serum paraoxonase-1 enzyme (PON-1) activity, arylesterase activity, the antioxidant-oxidant status in patients with PH and to compare with healthy controls.&#x0D; Material and Methods: Thirty five healthy ındividuals (mean age 45.7±5.9 years) as a control group and thirty eight patients (mean age 46.5±12.6 years) with a diagnosis of PH wereincluded in thestudy. Serum PON-1 and arylesterase activity, the total antioxidative capacity of plasma (TAC) and total oxidantstatus (TOS) were measured by using colorimetric methods. The Oxidative Stress Index (OSI) wascalculated as TOS/ TACX100.&#x0D; Results: Serum PON1 activity is significantly lower in PH patients when compared with healthy controls (p=0.001). The serum arylesterase activity and TAC, TOS and OSI status were similarin bothgroups. There is inverse correlation between serum PON1 activityand NYHA functionalcapacity (r:-0.649 p=0.001). Furthermore, PON1 activity of study patients are similarin the PH subgroups. Serum activity of PON1 wasfoundto bethe only independent parameter for the presence of PH in binary logistic regression analysis (OR 0.984, 95 % CI 0.977-0.992, p=0.001). Eight patients died follow up period (27.6±14.5 months) and none of theparametersincluding PON1 were associated with mortality.&#x0D; Conclusion: Serum PON1 activity of PH patients is lowerthanhealthypopulation, but does not predictmortality.&#x0D; Bangladesh Journal of Medical Science Vol.19(4) 2020 p.652-658

Evaluation of factors affecting sexual dysfunction in female patients with diabetes mellitus.

Our objective in this study was to evaluate the factors predicting female sexual dysfunction (FSD) in patients with diabetes mellitus (DM). The study included 149 women with DM. Sexual function was evaluated with the Female Sexual Function Index (FSFI) questionnaire, in which total scores under 26.55 characterized the occurrence of FSD (Group 1 > 26.55, Group 2 < 26.55). We recorded the patients' demographic, metabolic, and hormonal data. Ophthalmologic, neurologic, and renal complications were also evaluated. The antioxidant status of the patients in both groups was determined by measuring the activity of the enzymes paraoxonase-1 (PON-1) and arylesterase (ARE). Based on the FSFI scores, 60 patients were allocated to Group 1 (26.6 ± 12.3) and 89 to Group 2 (22.6 ± 9.5). Group 2 compared with Group 1 had significantly (p < 0.05) higher mean concentrations of glycated hemoglobin (HbA1c), glucose, triglycerides, and insulin, along with higher rates of metformin use, smoking, retinopathy, and nephropathy. The mean serum ARE concentrations were significantly lower in Group 2 compared with Group 1 (p = 0.000), but the mean serum PON-1 concentrations were similar between both groups (p = 0.218). On multivariable regression analysis, age, ARE activity, Beck Depression Inventory (BDI) score, and menopause were significant independent predictors of FSD (p < 0.05). In this study, we evaluated the predictive factors determining FSD caused by DM. Despite the significant results found in our study, future randomized controlled studies with a long follow-up and a larger number of patients are required to determine how DM affects FSD.

Prognostic Value of Insecticide Type and Enzymatic Activities on Severity of Acute Insecticides Poisoning

Background: Insecticides poisoning is a major problem worldwide, especially in developing countries. The most extensively utilized types are pseudocholinesterase (PChE) inhibitors, predominantly organophosphorus compounds and carbamates. They are metabolized by microsomal oxidases to oxygen analogues, which are active neurotoxic metabolites. These oxygen analogues are further hydrolyzed by the serum arylesterase; paraoxonase (PON1), which appears to play a pivotal role in their detoxification. Objectives: This study aimed to 1-Identification and quantitation of common insecticides in acutely poisoned patients presented to Assiut University hospitals. 2- Detection of paraoxonase and cholinesterase levels in poisoned patients. 3- Evaluate the prognostic value of pesticide type and enzymes level in relation to the severity of insecticidal poisoning. Methods: This case-control study was conducted on 50 patients who have been admitted to the Emergency Unit and Intensive Care Units in Assiut University Hospitals along with 50 controls. Age, residence and sex were matched. History and clinical data and other related laboratory investigations were gathered for each patient. Blood plasma samples (5ml) were collected from patients on admission alongside controls then analyzed for level of pseudocholinesterase (PChE) and paraoxonase (PON1) enzymes activity by a spectrophotometer. The insecticide types were identified using Gas Chromatography/Mass spectrometry (GC-MS). Results: The patients were mostly males, of young age group and residing in rural areas. The mode of poisoning was mainly accidental by oral route (66%). Tachycardia, tachypnea and hypotension were most commonly presenting muscarinic signs. The detected insecticides were mainly of the organophosphate types specifically malathion. A highly significant decrease in PChE and PON1 level were detected in patients compared to controls that the decline in their levels was also significantly associated with the severity of acute poisoning. A positive correlation was also observed between PChE and PON1 levels. Conclusion: the present study identified more than one type of pesticides mainly of organophosphate category among acutely poisoned patients. Furthermore, it pointed to those persons with higher paraoxonase activity and less cholinesterase inhibition may have a better chance of toxic effects amelioration

Paraoxonases (PON) 1, 2, and 3 Polymorphisms and PON-1 Activities in Patients with Sickle Cell Disease.

(1) Background: Oxidative stress, chronic inflammation, vasoocclusion, and free iron are all features present in sickle cell disease. Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action. Here, for the first time, we described PON-1 activities and PON-1, PON-2, PON-3 polymorphisms in patients with sickle cell disease, homozygous for HbSS, compared with healthy controls. (2) Methods: The groups were matched for age and gender. PON-1 activities (arylesterase and paraoxonase) were determined by enzymatic hydrolysis of phenylcetate and paraoxon, respectively. Polymorphisms were determined by Restriction Fragment Length Polymorphism- Polymerase Chain Reaction (RFLP-PCR). (3) Results: Plasma cholesterol and fractions, ApoA1 and ApoB levels were all decreased in sickle cell disease patients, while anti-oxidized low-density lipoprotein (LDL) antibodies and C-reactive protein were increased. Serum arylesterase activity was lower in sickle cell disease patients when compared with healthy controls. In patients, paraoxonase activity was higher in those with PON-1 RR Q192R polymorphism. In these patients, the increase of serum iron and ferritin levels and transferrin saturation were less pronounced than those observed in patients with QQ or QR polymorphism. No differences were observed with PON-1 L55M, and PON-2 and PON-3 polymorphisms. Multivariate regression analysis showed that transferrin and ferritin concentrations correlated with arylesterase and paraoxonase activities. (4) Conclusions: Both transferrin and ferritin were the main predictors of decreased arylesterase and paraoxonase activities in patients with sickle cell disease. LDL oxidation increased, and RR PON-1 Q192R polymorphism is likely to be a protective factor against oxidative damage in these patients.

Relationship of High-Density Lipoprotein-Associated Arylesterase Activity to Systolic Heart Failure in Patients with and without Type 2 Diabetes

High-density lipoprotein (HDL) confers protection against cardiovascular disease partly attributable to its robust anti-oxidant activities, which is largely impaired in diabetic conditions. In this study, we analyzed the anti-oxidant activity of HDL, as represented by the arylesterase activity of paraoxonase 1 (PON1) in HDL particles, in 216 consecutive HF patients with (n = 79) or without (n = 137) type 2 diabetes, and age- and gender-matched 112 diabetic and 189 non-diabetic non-HF controls. We found arylesterase activity was significantly decreased in patients with than without HF, and was further decreased when comorbid with diabetes. After adjusting for conventional risk factors and apolipoprotein A-I levels, arylesterase activity remained correlated positively with left ventricular ejection fraction in diabetic (r = 0.325, P = 0.020) but not non-diabetic patients (r = 0.089, P = 0.415), and negatively with NT-proBNP and NYHA functional class in both subgroups. In regression analyses, a higher risk of HF was observed in diabetic than non-diabetic patients when having low arylesterase activities. In conclusion, our data demonstrate that impaired serum arylesterase activity in patients with HF is further reduced when comorbid with diabetes. The relationship of impaired arylesterase activity to HF is especially enhanced in diabetic patients.

Angiotensin-converting enzyme insertion/deletion (rs106180) and angiotensin type 1 receptor A1166 C (rs106165) genotypes and psoriasis: Correlation with cellular immunity, lipid profile, and oxidative stress markers.

Psoriasis is a chronic inflammatory skin condition and angiotensin-converting enzyme (ACE) is a key circulating enzyme converting angiotensin (Ang) I to the vasoactive peptide Ang II. The exact role of ACE insertion (I)/deletion (D) polymorphism (rs106180) in psoriasis is not clear. We aimed to examine whether the ACE I/D and Ang II type 1 receptor (AT1R) A1166 C-polymorphisms (rs106165), lipid profile, and stress oxidative are associated with susceptibility to psoriasis. One hundred patients with psoriasis and 100 sex- and age-matched unrelated healthy controls were recruited for this case-control study. ACE I/D and AT1R A1166 C polymorphisms were identified by the polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively, malondialdehyde (MDA) was detected by the high-performance liquid chromatography, serum arylesterase (ARE) activity of paraoxonase and catalase activities were detected by the spectrophotometry, superoxide dismutase (SOD) activity and vascular adhesion protein (VAP)-1 were measured by ELISA. The presence of C allele of AT1R A1166 C and I allele of ACE considerably increased the risk of psoriasis by 6.42-fold (P < 0.001). The distribution of II-genotype of ACE was significantly higher in psoriasis patients than in control group and increased the risk of disease by 3.11-times (P = 0.023). The higher levels of MDA in patients and the higher activity of SOD, ARE, and CAT was observed in healthy controls with I/D+I/I-genotype of ACE I/D. This study for the first time demonstrated that the ACE I/D and AT1R A 1166 C genes polymorphisms robustly increases the risk of developing psoriasis in population from west of Iran. In addition, these individuals had significantly higher VAP-1 and MDA concentration and lower enzymatic and nonenzymatic antioxidant-status, suggesting that psoriatic patients carrying C allele of AT1R1166 polymorphism may be more susceptible to cardiovascular disease and myocardial infarction compared with A allele.

Ameliorating oxidative stress and inflammation by Hesperidin and vitamin E in doxorubicin induced cardiomyopathy

Abstract Background Doxorubicin (DOX) is a common chemotherapeutic drug. However, it causes cardiomyopathy which reduces its clinical use in human cancer therapy. Objective The purpose of our study was to assess the cardioprotective effect of hesperidin (HSP) and vitamin E (VIT.E) against DOX-induced cardiomyopathy. Material and methods Seventy rats were allocated into seven groups: control, HSP (50 mg/kg, orally), VIT.E (100 mg/kg orally), DOX [4 mg/kg, intraperitoneally (i.p.)], DOX+HSP, DOX+VIT.E and DOX+HSP+VIT.E. Results Our findings showed that serum lactate dehydrogenase (LDH), creatine kinase (CK), myeloperoxidase (MPO), cardiac catalase and caspase activities as well as cardiac malondialdehyde (MDA) and serum nitric oxide (NO) concentrations were reduced DOX+HSP or DOX+VIT.E or DOX+VIT.E+HSP groups compared to DOX group. Whereas, cardiac reduced glutathione (GSH) level, serum arylesterase, and paraoxonase activities were higher in rats injected with DOX and administrated with HSP and VIT.E than that of rats injected with DOX only. Cardiac histopathology of DOX group showed some changes that were improved during administration with HSP and VIT.E. Conclusion HSP and VIT.E possess a protective effect against DOX-induced cardiomyopathy via inhibiting oxidative stress, inflammation, and apoptosis.