Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia

2003 ◽  
Vol 170 (1) ◽  
pp. 21-29 ◽  
Author(s):  
J Beltowski
2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Małgorzata Trocha ◽  
Małgorzata Krzystek-Korpacka ◽  
Anna Merwid-Ląd ◽  
Beata Nowak ◽  
Małgorzata Pieśniewska ◽  
...  

Purpose. Ischemia/reperfusion (IR) is the main cause of liver damage after transplantation. We evaluated the effect of sitagliptin (STG) on oxidative stress parameters in the rat liver under IR. Methods. Rats were treated with STG (5 mg/kg) (S and SIR) or saline solution (C and CIR). Livers from CIR and SIR were subjected to ischemia (60 min) and reperfusion (24 h). During reperfusion, aminotransferases (ALT and AST) were determined in blood samples. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), paraoxonase-1 (PON1), glutathione peroxidase (GPx), and the mRNA expression of SOD1 were determined in liver homogenates after reperfusion. Different regions of livers were also histologically evaluated. Results. The PON1 activity was higher, and the TBARS level was lower in SIR than in CIR. There was an inverse relationship between TBARS and PON1 levels in the whole cohort. The GPx activity was lower in ischemic than in nonischemic groups regardless of the STG treatment. In SIR, the SOD1 activity was higher compared to that in CIR. In S, the expression of SOD1 mRNA was the highest of all examined groups and positively correlated with the SOD1 activity in the whole animal cohort. During IR aminotransferases, the activity in the drug-treated group was lower in all examined points of time. In drug-treated groups, the percentage of steatosis was higher than that in nontreated groups regardless of IR. Conclusions. The protective effect of STG on the rat liver, especially its antioxidant properties, was revealed under IR conditions.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Iwona Bednarz-Misa ◽  
Magdalena Mierzchala-Pasierb ◽  
Patrycja Lesnik ◽  
Sylwia Placzkowska ◽  
Krzysztof Kedzior ◽  
...  

Oxidative stress and uncontrolled inflammation are hallmarks of sepsis, leading to organ failure and death. As demonstrated in animal studies, oxidative stress can be alleviated by antioxidant therapies. Paraoxonase-1 (PON1) is a serum-based antioxidant, anti-inflammatory agent, detoxifier, and quorum-sensing factor found to be a prognostic marker in sepsis. However, its associations with multiple organ dysfunction syndrome (MODS), a complication of sepsis and the leading cause of death in the surgical intensive care units (ICU), as well as with specific organ dysfunction, infection site, and invading pathogen remain unknown. Therefore, we measured arylesterase activity of PON1 in 87 individuals (35 with MODS) and related it to the clinical type, organ failure, infection site, pathogens, and hematological and biochemical indices of inflammation at admission to ICU and during a five-day follow-up. Suitability of PON1 and its indices derived from a follow-up as biomarkers in MODS was evaluated as well. MODS was associated with decreased PON1, more so in patients with septic shock, displaying an excellent accuracy as a marker of MODS (91%) and a fair one as a marker in differentiating septic shock from severe sepsis (76%). Decreased admission PON1 accompanied cardiovascular insufficiency (CVI), and, as its marker, PON1 displayed a good accuracy (82%). It was also associated with the abdomen as a site of infection but not with an invading pathogen. In multivariate analysis, 50% of variability in PON1 activity in patients with MODS was explained by the patients’ age, CVI, and abdomen as a site of infection. Patients with septic shock, CVI, and abdominal MODS had distinctly different dynamics of PON1 during a follow-up. Mean PON1 activity during the follow-up reflected the associations observed for admission PON1 but was also significantly associated with metabolic dysfunction. Our results show PON1 potential as a biomarker in MODS, particularly as an indicator of CVI.


Author(s):  
Vahid Pourshafiei ◽  
Vahide Jamshidi ◽  
Ameneh Khodarahmi ◽  
Mahmood Vakili

Background and Aims: This study aimed to investigate the frequency of Q192R polymorphism and oxidative stress markers in infants with glucose-6phosphate dehydrogenase (G6PD) deficiency. Materials and Methods: This is a case-control study in which 60 male infants (2-4 months old) with G6PD deficiency along with 60 age- and sexmatched healthy neonates were included. The diagnosis of G6PD deficiency was made by Beutler test by which the G6PD enzyme activity is measured by the fluorescent spot test. The blood samples were taken from all infants, and the sera were isolated for the evaluation of Paraoxonase-1 (PON1) and malondialdehyde (MDA) using the spectrophotometric method. Restriction fragment length polymorphism was applied for determination of Q192R polymorphism (rs 662). Results: The frequencies of QQ, QR, and RR genotypes were 55%, 39%, and 6%, respectively in infants with G6PD deficiency while the above genotype frequencies were 45%, 49%, and 6%, respectively in healthy neonates. The frequency of R and T alleles failed to show any significant difference when G6PD deficient infants and healthy neonates were compared. The results indicated PON1 activity and MDA levels being significantly (p<0.05) higher in neonates with G6PD deficiency compared with their healthy counterparts. Conclusion: Contrary to previous studies, it was indicated that the presence of RQ and RR genotypes at Q192R position is associated with decreased activity of PON1 and increased oxidative stress. In this study, no significant differences were found in the genotype and allele frequency of PON1 Q192R polymorphism between the case and control groups. Also, this frequency was not consistent with the results obtained from oxidative stress conditions.


2014 ◽  
Vol 33 (11) ◽  
pp. 1134-1140 ◽  
Author(s):  
S Karadas ◽  
M Aslan ◽  
H Gonullu ◽  
C Kati ◽  
L Duran ◽  
...  

Background: Acetaminophen is at present one of the most commonly used analgesics and antipyretics. Recent evidence has suggested that oxidative stress is involved in the mechanism of acetaminophen intoxication. Paraoxonase-1 (PON1) plays an important role as an endogenous free-radical scavenging molecule. The aim of this study was to evaluate the influence of serum PON1 activity and oxidative stress in patients with acetaminophen intoxication. Methods: A total of 20 patients with acetaminophen intoxication and 25 healthy controls were enrolled. Serum total antioxidant capacity (TAC), lipid hydroperoxide (LOOH) levels, and paraoxonase and arylesterase activities were measured spectrophotometrically. Results: The serum TAC levels and the paraoxonase and arylesterase activities were significantly lower in patients with acetaminophen intoxication compared with controls (all, p < 0.001), while the serum LOOH levels were significantly higher ( p < 0.001). Conclusions: Our results suggest that decreased PON1 activity seems to be associated with increased oxidative stress in patients with acetaminophen intoxication. Measuring serum PON1 activity may be useful in assessing the development of toxicity risk in acetaminophen toxicity. It would be useful to recommend vitamins with antioxidant effects such as vitamins C and E along with medical treatments.


2016 ◽  
Vol 36 (7) ◽  
pp. 663-669
Author(s):  
S Karadas ◽  
M Aslan ◽  
MR Ceylan ◽  
M Sunnetcioglu ◽  
N Bozan ◽  
...  

Introduction: Anthrax is a bacterial disease caused by the aerobic sporeforming bacterium Bacillus anthracis. It has been suggested that oxidative stress plays an important role in the pathogenesis of B. anthracis. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity, catalase activity, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) levels in patients with cutaneous anthrax. Materials and methods: Fifteen patients with cutaneous anthrax and 15 healthy controls were enrolled in this study. The serum MDA levels, SOD levels, paraoxonase, arylesterase, and catalase activities were measured using a spectrophotometer. Results: The serum SOD levels, paraoxonase, arylesterase, and catalase activities were significantly lower in patients with cutaneous anthrax than in controls (for all, p < 0.001), whereas MDA levels were significantly higher ( p < 0.001). No significant correlation was found between serum paraoxonase activity, arylesterase activity, SOD levels, and MDA levels (all, p > 0.05) in patients with cutaneous anthrax. Conclusions: The current study was the first to show decreased antioxidant levels and increased oxidant levels in patients with cutaneous anthrax. Therefore, decreased PON1 activity may play a role in the pathogenesis of cutaneous anthrax.


2018 ◽  
Vol 8 (2) ◽  
pp. 91-97 ◽  
Author(s):  
Hassan Ahmadvand ◽  
Esmaeel Babaeenezhad ◽  
Maryam Nasri ◽  
Leila Jafaripour ◽  
Reza Mohammadrezaei Khorramabadi

Introduction: Glutathione (GSH) protects the tissue and cell from oxidative injury. Objectives: In the current study, we investigated the possible effects of GSH on liver markers, oxidative stress and inflammatory indices in rat with renal ischemia reperfusion (RIR) injury. Materials and Methods: Twenty-four adult male Wistar rats were divided into 3 groups (n=8). Group I (the control group), group II (the RIR group) received saline (0.25 mL/d, intraperitoneally; i.p.), group III as the RIR group that received GSH (100 mg/kg/d, i.p.). The treatment with saline or GSH began daily 14 days before RIR induction. RIR was induced by clamping renal pedicles for 45 minutes and 24 hours of reperfusion. Results: RIR significantly increased the serum level of nitric oxide (NO), the serum activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), the serum and renal levels of malondialdehyde (MDA), and the serum activity of myeloperoxidase (MPO). However, RIR significantly decreased the serum and renal levels of GSH, serum paraoxonase 1 (PON1) activity, and the serum and renal activities of catalase (CAT) and glutathione peroxidase (GPX). GSH administration could significantly improve the serum activities of AST, GGT, MPO, GPX and PON1 and serum levels of NO, renal MDA, GSH levels, and serum and also renal CAT activities. Conclusion: Our study indicated that GSH administration ameliorated RIR injury in rats by improving the activities of liver markers and antioxidant enzymes, the levels of MDA, NO, GSH and MPO activity.


2020 ◽  
Vol 19 (4) ◽  
pp. 652-658
Author(s):  
Muhsin Kalyoncuoglu ◽  
Murat Baskurt ◽  
Aysem Kaya ◽  
Gunes M Dogan ◽  
Okay Abacl ◽  
...  

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. 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. 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. Conclusion: Serum PON1 activity of PH patients is lowerthanhealthypopulation, but does not predictmortality. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.652-658


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Suzana Bojic ◽  
Jelena Kotur-Stevuljevic ◽  
Nevena Kalezic ◽  
Zorana Jelic-Ivanovic ◽  
Aleksandra Stefanovic ◽  
...  

Introduction. State of severe oxidative stress is encountered in sepsis. Paraoxonase 1 (PON1) protects against oxidative stress but also undergoes inactivation upon that condition. We investigated PON1 activity in surgical patients with sepsis in relation to oxidative stress status, inflammation, disease severity, and survival.Methods. Prospective observational study. Sixty-nine surgical patients with sepsis were compared to 69 age/sex matched healthy controls. PON1 paraoxonase and diazoxonase activities, selected biochemical, hematological and oxidative stress parameters were measured on admission to ICU and 24, 48, 72, and 96 hours later. Disease severity scores were calculated daily.Results. Septic patients had significantly lower PON1 activities compared to control group at all time points. PON1 activities had good capacity to differentiate septic patients from healthy controls. Low PON1 activities were associated with higher disease severity scores and higher risk of death. Correlation between PON1 activity and markers of inflammation failed to reach significance. Decrease in PON1 activity was correlated with an increase in reducing components in plasma.Conclusion. Our study demonstrated lower PON1 activity in surgical patients with sepsis compared to healthy controls. PON1 activity also reflected severity of the disease. Low PON1 activity was associated with higher mortality of surgical patients with sepsis.


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