Evaluation of enzymatic and non-enzymatic antioxidant status and biomarkers of oxidative stress in saliva of patients with oral squamous cell carcinoma and oral leukoplakia: a pilot study.

Objective: The study aimed to evaluate total antioxidant capacity as well as levels of various enzymatic and non-enzymatic antioxidants, and oxidative stress markers in saliva of patients with oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL). Material and methods: Twenty patients with OSCC, 20 patients with OL and 20 healthy subjects were enrolled into this prospective study. Total Antioxidant Capacity (TAC), activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) as well as levels of total glutathione (tGSH), reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, uric acid (UA), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were estimated in saliva using appropriate biochemical methods. Results: The activity of SOD was significantly higher in OSCC group in comparison with OL and control groups. The levels of GSH were markedly lower in OSCC and OL patients as compared to the control group. Likewise, we found that GSH/GSSG ratio was markedly lower in the OSCC and OL groups. Levels of some biomarkers were influenced by clinical staging of OSCC and OL as well as by sociodemographic factors. Conclusions: The results of this pilot study suggest that salivary activity of SOD is higher in OSCC patients, whereas levels of GSH and GSH/GSSG ratio are lower in saliva of patients with OSCC and OL. Clinical staging of OSCC and OL, as well as some sociodemographic factors may also influence salivary antioxidant status.

Boronate Affinity Chromatography Accurately Measures HbA1c also in Patients with End-Stage Renal Disease - Performance Evaluation of the A1c HPLC Analyzer.

BACKGROUND: Boronate affinity chromatography is widely used, and the method has lately been improved and designed for HbA1c measurements. We report performance evaluation of the affinity chromatography HbA1c HPLC analyzer. METHODS: Within- and between-run imprecision was assessed based on the results of a series of measurements in three different EDTA blood samples and in control materials. HbA1c levels were measured and compared in 349 EDTA blood samples and 50 samples from patients with end-stage renal disease (ESRD) using the Premier Hb9210 analyzer (affinity chromatography) and the D-10 Hemoglobin Testing System (ion-exchange chromatography). RESULTS: The within- and between-run imprecision CVs ranged from 0.72% to 2.01%. Median HbA1c level measured by the Premier Hb9210 was significantly lower (6.4% [46 mmol/mol] vs. 6.6% [49 mmol/mol], p < 0.001). The Passing-Bablok agreement test yielded a slope of 1.0 (95% CI: 1.0 to 1.0) and intercept of -0.1 (95% CI: -0.1 to -0.1). Correlation coefficient and the mean difference amounted to 0.992 and -0.13% (95% CI: -0.11 to -0.15), respectively. Similar results were obtained for HbA1c levels < 7% [< 53 mmol/mol] and ≥ 7% [≥ 53 mmol/mol]. In ESRD patients, median HbA1c level measured by the Premier Hb9210 was also significantly lower (6.0% [42 mmol/mol] vs. 6.5 [48 mmol/mol], p < 0.001) with the mean difference equal to -0.52% (95% CI: -0.59 to -0.46). CONCLUSIONS: Although the Premier Hb9210 gave lower HbA1c levels, good results agreement with the D-10 Hemoglobin Testing System was found. Analytical performance found for HbA1c measurements in ESRD patients was similar. The Premier Hb9210 analyzer is suitable for routine HbA1c testing in clinical practice.

Diagnostic and prognostic relevance of microparticles in peripheral and uterine blood of patients with endometrial cancer.

OBJECTIVES: Exosomes - microvesicles which are secreted by living cells - can be produced from different cell types and detected in various body fluids. They are the carriers of intercellular information which regulate tumor microenvironment and are considered to be involved in tumor progression and metastasis. Cancer cells can secrete more exosomes than healthy cells, and are expected to be potential tools for tumor diagnosis and treatment. MATERIAL AND METHODS: In this report, we present the results of microparticle analysis in peripheral and uterine blood of patients with endometrial cancer. To the best of our knowledge, this study has been the first to report microvesicle status in peripheral and uterine blood samples. The aim of the study was to determine the amount of total (TF+), endothelial (CD144+) and monocytic (CD14+) microparticles. The counting of the selected microparticles in citrate plasma was performed using flow cytometry on the BD Canto II cytometer. RESULTS: We found that the total amount of microparticles in cancer patients was much higher than in healthy controls. Moreover, microparticle count in uterine blood was higher than in peripheral blood of patients with endometrial cancer. We also demonstrated that the amount of microparticles correlates with the histologic grade and clinical stage of the tumor. CONCLUSIONS: The most interesting finding in this work was the high level of TF, CD144 and CD14 MPs in uterine blood samples. Thus we can consider the monocyte-macrophage-derived MPs as a candidate marker of endometrial cancer and maybe very critical part of the endometrial carcinogenesis.

HBK-14 and HBK-15 with antidepressant-like and/or memory-enhancing properties increase serotonin levels in the hippocampus after chronic treatment in mice.

5-HT1A and 5-HT7 receptor ligands might have antidepressant-like properties and improve cognitive function. We previously reported significant antidepressant- and anxiolytic-like effects of two dual 5-HT1A and 5-HT7 receptor antagonists in various behavioral tests in rodents. As a continuation of our previous experiments, in this study we aimed to investigate whether chronic administration of 1-[(2,6-dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15) caused antidepressant-like effects and elevated serotonin levels in the murine hippocampus. We also evaluated cholinolytic properties and the influence of acute administration of both compounds on cognitive function in mice. To assess antidepressant-like properties and the influence on learning and memory we used forced swim test and step-through passive avoidance task in mice, respectively. Both compounds showed antidepressant-like properties and significantly elevated serotonin levels in the hippocampus after chronic treatment (HBK-14 - 2.5 mg/kg; HBK-15 - 0.625 and 1.25 mg/kg). HBK-15 administered chronically antidepressant-like activity at lower dose (0.625 mg/kg) than the dose active after acute treatment (1.25 mg/kg). None of the compounds affected locomotor activity of mice. HBK-15 possessed very weak cholinolytic properties, whereas HBK-14 did not show any effect on muscarinic receptors. Only HBK-15 (0.625 mg/kg) presented memory-enhancing properties and ameliorated cognitive impairments caused by scopolamine (1 mg/kg). Our results indicate that 5-HT1A and 5-HT7 antagonists might have potential in the treatment of depression and possess positive influence on cognitive function.

The use of selected neutrophil protein plasma concentrations in the diagnosis of Crohn's disease and ulcerative colitis - a preliminary report.

BACKGROUND: Difficulties in diagnosis of inflammatory bowel disease (IBD) motivate the search for new diagnostic tools, including laboratory tests. The aim of this study was to evaluate concentrations of the neutrophil (NEU) proteins leukocyte elastase (HLE-α1AT), lactoferrin and calprotectin as potential biomarkers used in the diagnosis and assessment of clinical activity of Crohn's disease (CD) and ulcerative colitis (UC). MATERIAL/METHODS: The study included 27 patients with CD, 33 patients with UC and 20 healthy controls. Plasma concentrations of calprotectin, lactoferrin and HLE-α1AT were measured using ELISA. RESULTS: In patients with CD higher concentrations of HLE-α1AT (64.3±43.1 vs. 30.1±7.7 ng/l, P<0.001), calprotectin (151.6±97.8 vs. 69.9±22.1 ng/l, P<0.001) and lactoferrin (243.2±102.0 vs. 129.7±32.7 ng/l, P<0.001) than in the control group were found. In patients with UC higher plasma concentrations of HLE-α1AT (62.0±30.9 vs. 30.1±7.7 ng/l, P<0.001), calprotectin (149.6±72.3 vs. 69.9±22.1 ng/l, P<0.001) and lactoferrin (242.6±107.5 vs 129.7±32.7 ng/l, P<0.001) than in the control group were found. HLE-α1AT/NEU and lactoferrin/NEU ratios in patients with UC were significantly higher compared with patients with CD. Calprotectin (P=0.010) and lactoferrin (P=0.023) levels were higher in patients with the active compared with inactive phase of CD. CONCLUSIONS: The diagnostic characteristics of plasma granulocyte protein concentrations indicate the usefulness of these tests in the diagnosis of IBD. Higher HLE-α1AT and lactoferrin/NEU ratios in patients with UC than with CD may suggest the usefulness of these ratios in differential diagnostics. Plasma calprotectin and lactoferrin levels may be useful in CD activity assessment.

Influence of analgesic active 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one on the antioxidant status, glucose utilization and lipid accumulation in some in vitro and ex vivo assays.

PURPOSE: Earlier we demonstrated that 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) elevates nociceptive thresholds in the mouse model of diabetic neuropathic pain. Since drug-induced impairments of glucose and lipid metabolism and the oxidative stress might diminish benefits from analgesia achieved by analgesic drugs used in diabetic neuropathy, the effect of LPP1 on glucose utilization, lipid accumulation and its antioxidant and cytotoxic potential were assessed in some in vitro and ex vivo tests. METHODS: Total antioxidant capacity was evaluated spectrophotometrically using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method, whereas the activities of glutathione (GSH) peroxidase and reductase were measured using methods based on the oxidation of NADPH to NADP. The spectrophotometric method for the evaluation of GSH level in mouse brain tissue homogenates involved the oxidation of GSH by the sulfhydryl reagent 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) to form a yellow derivative, 5'-thio-2-nitrobenzoic acid (TNB), measurable at 412 nm. Cytotoxicity and glucose utilization were measured in hepatoma HepG2 cells and in 3T3-L1 adipocytes. Lipid accumulation was measured in 3T3-L1 cell lines. RESULTS: LPP1 had dose-dependent antioxidant properties in DPPH radical assay (14-22% versus control; p < 0.001). Its single administration caused an increase in GSH concentration in brain tissue homogenates of mice by 34% (versus control group; p < 0.05). LPP1 was not cytotoxic and it did not increase glucose utilization or lipid accumulation in cell cultures. CONCLUSIONS: Previously demonstrated antinociceptive properties of LPP1 are accompanied by a lack of cytotoxicity. LPP1 does not impair glucose or lipid metabolism and is an antioxidant. All these properties might be advantageous for its use in diabetic neuropathy.

[Diagnostic importance of pentraxins at the early phase of acute pancreatitis]. / Znaczenie pentraksyn we wczesnej diagnostyce ostrego zapalenia trzustki.

Pentraxins are among the main acute phase reactants. There are two types of pentraxins, i.e., long, including pentraxin 3 (PTX3) and short, including C-reactive protein (CRP) and serum amyloid A (SAA). The aim of the study was to assess the increase in serum concentrations of pentraxins (ex- pressed as the multiplicity of the upper reference limits) and their usefulness in prognosing severe course of acute pancreatitis (AP) in the early phase of the disease. Forty patients admitted to Ist Department of Surgery, Jagiel-Ionian University Medical College with the diagnosis of AP were recruited for the study. In the early phase of AP, the concentrations of PTX3 achieved maximum earlier than CRP or SAA, enabling to differentiate between mild and moderate or severe AP in the first day of the disease. Also, during the first 24 hours from beginning of AP, SAA achieved its best prognostic value. Of all pentraxins studied, SAA was characterized by the most significant increase as compared to the upper reference limit. The prognostic utility of CRP increased later, after 48 hours of AP.

Plasma pentraxin 3 concentrations in patients with acute pancreatitis.

BACKGROUND: Pentraxin 3 (PTX3) belongs to the acute phase proteins; its concentration increases significantly in the early stages of inflammation. In nearly 20% of patients with acute pancreatitis (AP) escalated inflammation leads to the development of severe forms of the disease. The aim of this study was to evaluate the pattern of changes in PTX3 concentration in patients with AP at the early stage of the disease (first 5 days from admission) and to assess the relationship between PTX3 and other inflammatory markers. METHODS: The study included 40 patients with AP (16 women and 24 men)--12 with severe and 28 with mild form of AP. Concentrations of PTX3, serum amyloid A (SAA), C-reactive protein (CRP), hepatocyte growth factor (HGF), procalcitonin (PCT), polymorphonuclear elastase (PMN-elastase), interleukin 6 (IL-6), interleukin 18 (IL-18), and soluble receptor for TNFalpha (sTNFR75) were measured in samples collected on the 1st, 3rd, and 5th day of the hospital stay. Plasma PTX3 was measured also in the control group, consisting of 37 age and sex-matched healthy subjects. RESULTS: The highest concentrations of PTX3 were noted on the first day after admission. The concentrations were higher in patients with the severe compared to those with the mild form of AP (median 17.2 vs. 4.0 ng/mL on day 1, p = 0.03; 6.1 vs. 2.2 on day 5, p = 0.044). On each of the study days significant correlations were found between PTX3 and SAA, IL-6, and PMN-elastase (p < 0.05). CONCLUSIONS: The pattern of changes in PTX3 concentration in the early phase of AP is similar to that of IL-6, and its peak levels are achieved earlier compared to CRP. Our findings suggest that PTX3 may be useful in early evaluation and prediction of the severity of AP.

Fibroblast Growth Factor 21 in Gestational Diabetes Mellitus and Type 2 Diabetes Mellitus.

Objective: Women who develop GDM present a metabolic condition similar to that found in type 2 diabetes, characterized by impaired insulin response. Due to similar pathophysiologic mechanisms found between type 2DM and GDM, there is a great interest in finding markers that will lead to the understanding of a possible common origin to both diseases. The aim of this study was to determine serum FGF21 levels in 2DM and GDM and its correlation with selected metabolic parameters. Method: The study included 54 2DM patients and 52 nondiabetic individuals (control group 1) as well as 74 GDM women and 32 healthy pregnant controls (control group 2). Serum FGF21 was determined by enzyme-linked immunosorbent assay (ELISA), in all groups, and correlated with biochemical parameters of glucose metabolism and insulin resistance (HbA1c, HOMA index, TG, and HDL cholesterol). Results: FGF21 concentration was significantly higher in 2DM as compared with control group 1 (p < 0.01). In the 2DM group, FGF21 was positively correlated with HOMA index (p = 0.022, R = 0.398). In the GDM group, the positive relationships with FGF21 were observed with glucose (p = 0.020, R = 0.264) and TG (p = 0.013, R = 0.283) while HDL-C levels were correlated negatively (p = 0.004, R = -0.326). Conclusion: Serum FGF21 levels were significantly higher in 2DM patients than those without diabetes. Moreover, serum FGF21 levels were associated with selected metabolic parameters, suggesting that it may play acrolein glucose and lipid metabolism.

Salivary matrix metalloproteinase-9 (MMP-9) as a biomarker of periodontitis in pregnant patients with diabetes.

BACKGROUND: Pregnancy and diabetes increase the risk of developing pathological conditions in the periodontium. Salivary biomarkers, such as matrix metalloproteinase-9 (MMP-9), as well as antioxidants can be used as diagnostic indicators in monitoring periodontitis. OBJECTIVES: The aim of the study was to assess the periodontal status of pregnant women with regard to the presence of diabetes. In addition, we aimed to assess antioxidant activity and the level of MMP-9 in saliva in order to establish the optimal noninvasive determinants of periodontitis. MATERIAL AND METHODS: The study included 104 pregnant women: 35 patients had gestational diabetes mellitus (GDM); 30 patients had type 1 diabetes (T1D); and 39 patients did not have diabetes (the control group). The physical examination included the assessment of the approximal plaque index (API), the gingival index (GI), bleeding on probing (BOP), the probing pocket depth (PPD), and clinical attachment loss (CAL). In the saliva study, MMP-9 concentration as well as the ferric reducing ability of plasma (FRAP), and the activity of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPX) were measured. RESULTS: The pregnant patients with GDM and T1D had higher GI, BOP, PPD, and CAL scores than the control women (p < 0.0001, p = 0.0040, p = 0.0100, p = 0.0030, and p < 0.0001, p < 0.0009, p < 0.0001, p < 0.0001, respectively). The T1D patients had higher API scores as compared to the control women (p = 0.0010). The patients with periodontitis had higher salivary MMP-9 levels than the patients without periodontitis (p = 0.0001). The salivary antioxidant levels and activity were comparable among the study groups. The determinants of periodontitis (p < 0.0001) were MMP-9 concentration (p = 0.0008) and oral hygiene (p = 0.0001). The concentration of MMP-9 was also a useful determiner of the presence of periodontitis (p < 0.0001). CONCLUSIONS: In the pregnant women with diabetes, we observed worse gingival conditions, deeper periodontal pockets and greater attachment loss in comparison with the women from the control group. The concentration of MMP-9 in saliva is a good predictor of periodontitis and might be a useful tool for diagnosing periodontitis.

Angiogenic and Microvascular Status Alterations after Endovascular Revascularization of Lower Limb Arteries among Patients with Diabetic Foot Syndrome: A Prospective 12-Month Follow-Up Study.

Peripheral arterial disease (PAD)-induced ischemia is an important component of diabetic foot syndrome (DFS). The results of revascularization of the lower extremity arteries (including percutaneous transluminal angioplasty [PTA]) do not always give satisfactory long-term results, which is due to many factors. The aim of the study was to investigate the alterations in selected circulating angiogenic factors and microcirculation parameters in 41 patients with DFS following PTA and analyze their relationships with clinical outcomes during 1-year follow-up. Our study revealed a general decrease in pro-angiogenic factor levels after PTA and their subsequent stabilization during subsequent observation. The results indicated a significant association between plasma circulating FGF-2 level and poor outcomes (including the incidence of restenosis/reocclusion of treated arteries) during 12 months of observation. The perioperative changes in FGF-2 showed a significant association with LDF alterations after PTA. Follow-up 1-3 months post-intervention showed a tendency towards elevated TcpO2, VEGF-A, and VEGF-R2 levels in patients free from adverse events. These results may provide a basis for further research on the potential use of selected circulating angiogenic factors for monitoring the treatment of patients with DFS following PTA.

Serum inflammatory markers in the diagnosis and assessment of Crohn's disease activity.

INTRODUCTION: The aim of our study was to evaluate the diagnostic characteristics of selected inflammatory markers and the results of multiplication of their concentrations in the diagnosis and assessment of Crohn's disease (CD) activity. METHODS: We studied 49 patients with CD and 31 healthy controls. The CD patients were assigned to subgroups with active and inactive disease based on the Crohn's Disease Activity Index score. Serum interleukins and C-reactive protein (CRP) were measured using immunoassays. RESULTS: Serum CRP and interleukins: IL-6, IL-17A, IL-23 were significantly higher in the CD group than in controls, with the best diagnostic performance for IL-23. Only serum IL-6 and CRP were significantly higher in active than in inactive disease, with the better performance of CRP. Multiplication results did not perform better than individual multipliers. CONCLUSIONS: Serum CRP may be useful in the assessment of CD activity and there is a need for introduction of IL-23 for the CD diagnosis.

Cadmium-induced oxidative stress in Prussian carp (Carassius gibelio Bloch) hepatopancreas: ameliorating effect of melatonin.

The oxidative status of the hepatopancreas of Prussian carp females (Carassius gibelio) co-exposed to sublethal cadmium in water and melatonin was studied. The activities of antioxidant enzymes such as glutathione reductase (GR), glutathione peroxidase (GPx), and superoxide dismutase (SOD) as well as the concentration of reduced glutathione (GSH) were measured in homogenates of the hepatopancreas. Furthermore, concentrations of cadmium (Cd), zinc (Zn), copper (Cu), and iron (Fe) in the hepatopancreas were assayed. These females received melatonin implants and were exposed to 0.4 mg/L or 4.0 mg/L Cd in water for either a 13- or a 7-week period, followed by further 6 weeks of purification in clear water. Exposure to Cd influenced the increase in this metal concentration in fish hepatopancreas. In contrast, the fish exposed to cadmium with additional administration of melatonin had a lower accumulation of this metal. Exposure to Cd caused the increase in GSH content and the activity of GR, and a reduction in GPx activity, whereas the SOD activity varies depending on the exposure time on cadmium. In the hepatopancreas of fish treated with Cd alone, the content of Cu and Zn were increased and that of Fe was changed. After melatonin administration to Cd-exposed fish, a decrease in copper and zinc hepatopancreas content was noted. The present findings imply that melatonin co-treatment can effectively protect the fish against the toxic effects of cadmium on endogenous antioxidant status in hepatopancreas tissues and variations in metal concentration, such as Zn, Cu, and Fe.

Redox Balance Correlates with Nutritional Status among Patients with End-Stage Renal Disease Treated with Maintenance Hemodialysis.

Over 50% of end-stage renal disease (ESRD) patients die of cardiovascular disease. ESRD patients treated with maintenance hemodialysis are repeatedly exposed to oxidative stress. The aim of the study was to find the relationship between lifestyle factors, nutritional status, calcium-phosphate metabolism, and selected redox parameters such as glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), uric acid (UA), and total antioxidant capacity expressed as ferric reducing antioxidant power (FRAP). The study included 97 ESRD hemodialysis patients and 42 controls with no renal disease. Patients were asked to complete a questionnaire which gathered information on their physical activity, hours of sleep, smoking, and frequency of fruit and vegetable intake; the blood samples were then drawn before the midweek dialysis session. The ESRD patients had lower levels of GR, GPx, and SOD activity, a lower level of FRAP, and a higher UA concentration than the control group. The FRAP value decreased with age (ρ = -0.32, p = 0.001); smokers had a significantly lower SOD activity in comparison to nonsmokers (p = 0.03). In the ESRD patients, FRAP and UA correlated with both albumin (ρ = 0.26, p = 0.011; ρ = 0.41, p = 0.006, respectively) and prealbumin (ρ = 0.34, p ≤ 0.001; ρ = 0.28, p = 0.006, respectively), whereas UA, GR, GPx, and SOD correlated with calcium, UA, GR, and GPx with phosphate level. Based on the findings, there are weak associations between nutritional status and selected redox parameters in hemodialyzed patients. Further studies are needed to establish if diet modifications and adequate nutritional status can positively impact the antioxidant capacity in this group of patients.

Malnutrition, Inflammation, Atherosclerosis Syndrome (MIA) and Diet Recommendations among End-Stage Renal Disease Patients Treated with Maintenance Hemodialysis.

Malnutrition-inflammation-atherosclerosis syndrome is one of the causes of increased mortality in chronic kidney disease (CKD). The aim of the study was to assess the inflammation and nutritional status of patients in end-stage kidney disease treated with maintenance hemodialysis. The study included a group of 98 hemodialyzed patients with stage 5 CKD (38 women and 60 men). Albumin, prealbumin (PRE), and C-reactive protein (CRP) were measured in serum samples collected before mid-week dialysis. Fruit and vegetables frequency intakes were assessed with a questionnaire. CRP was above the reference limit of 5 mg/L in 53% of patients. Moreover, the Glasgow Prognostic Score (GPS) indicated the co-occurrence of inflammation and protein calorie malnutrition in 11% of patients, and the presence of either inflammation or malnutrition in 25%. The questionnaire revealed that hemodialyzed patients frequently exclude fruit and vegetables from their diets. Nearly 43% of the interviewed patients declared frequently eating vegetables, and 35% declared frequently eating fruit, a few times per week or less. The most frequently selected fruit and vegetables had a low antioxidant capacity. The strict dietary restrictions in CKD are difficult to fulfill, and if strictly followed, may lead to protein-calorie malnutrition.

Relation of the protein glycation, oxidation and nitration to the osteocalcin level in obese subjects.

Carboxylated osteocalcin (Gla-OC) contributes to the bone formation, whereas its undercarboxylated form (Glu-OC) takes part in the energy metabolism. In vitro studies had shown that treatment of osteoblast-like cells with advanced glycation end product-modified bovine serum resulted in reduced synthesis of collagen 1 and osteocalcin. The aim of this study was to find association between Gla-OC and markers of protein glycation, oxidation and nitration, as well as pro-inflammatory and antioxidant defense markers in obese subjects. Non-obese [(body mass index (BMI)<30 kg/m; n=34)] and obese subjects (30

Evaluation of antinociceptive and antioxidant properties of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one in mice.

The aim of this study was to evaluate the influence of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) on nociceptive thresholds in mouse models of persistent pain. Influence of LPP1 on motor coordination and its antioxidant capacity in mouse brain tissue homogenates were also assessed. Pain sensitivity thresholds in animals treated with LPP1 were established using 5 % formalin solution in normoglycemic mice and in streptozotocin (STZ)-treated diabetic mice in the von Frey, hot plate, innocuous, and noxious cold water tests (water at 10 °C and 4 °C, respectively). Motor deficits were assessed in the rotarod test, whereas antioxidant capacities were evaluated using ferric reducing ability of plasma (FRAP) assay, catalase (CAT), and superoxide dismutase (SOD) activities. LPP1was antinociceptive in both phases of the formalin test, in particular, in the late phase (at doses 0.9-30 mg/kg for 66-99 % vs. control normoglycemic mice) and in a statistically significant manner increased nociceptive thresholds in response to mechanical, heat, and noxious cold stimulation in neuropathic mice (at 30 mg/kg for 274, 192, and 316 %, respectively vs. diabetic control). LPP1 did not impair motor coordination of mice in the rotarod revolving at 6 or 18 rpm. In brain tissue homogenates, it demonstrated antioxidant capacity in FRAP assay and increased SOD activity for 63 % (acute administration) and 28 % (chronic administration) vs. control. No influence on CAT activity was observed. LPP1 has significant antinociceptive properties in the formalin model and elevates pain thresholds in neuropathic mice. It has antioxidant capacity and is devoid of negative influence on animals' motor coordination.