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3.
Pol J Pathol ; 66(3): 231-8, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26619101

ABSTRACT

Chronic hepatitis C (CHC) is accompanied by numerous metabolic disorders, partially associated with altered adipokine system regulation. Omentin (intelectin-1) is a novel adipokine known to play a pivotal role in metabolic regulation in CHC. In a group of 63 CHC patients (29 men/34 women) infected with genotype 1b, aged 6.6 ± 14.6 years, serum omentin levels and its gene expression in liver tissue were examined and their association with metabolic and histopathological features was assessed. Serum omentin levels were significantly higher in CHC patients compared to controls (p < 0.001), regardless of sex, body mass index (BMI), insulin sensitivity and lipid concentrations. There was no correlation between serum omentin and omentin hepatic expression. Neither parameter was associated with any histological features. Serum omentin in non-obese CHC patients seems not to be related to metabolic disorders or liver pathology. Omentin hepatic expression shows no relationship with either serum omentin levels or histopathological features. This suggests different mechanisms regulating circulating omentin concentration and omentin hepatic expression in CHC.


Subject(s)
Cytokines/biosynthesis , Hepatitis C, Chronic/metabolism , Lectins/biosynthesis , Adult , Aged , Cytokines/analysis , Female , GPI-Linked Proteins/analysis , GPI-Linked Proteins/biosynthesis , Hepatitis C, Chronic/pathology , Humans , Lectins/analysis , Liver/metabolism , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Young Adult
4.
Mol Med Rep ; 12(2): 2275-82, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25873273

ABSTRACT

Obesity is associated with an increased risk of certain types of cancer, including colon cancer. Adipose tissue is an endocrine organ that produces biologically active substances, such as leptin and ghrelin. Recent research has suggested that adipose-derived hormones may be associated with mechanisms linked to tumorigenesis and cancer progression. Furthermore, previous studies have demonstrated that pineal gland-derived melatonin possesses important oncostatic and antioxidant properties. The present study aimed to determine the effects of the adipokines ghrelin and leptin, and the melatonin on intracellular levels of reactive oxygen species (ROS) and the activity of selected antioxidant enzymes, such as superoxide dismutase, catalase (CAT) and glutathione peroxidase. The effects of these compounds were also determined on the viability of HCT 116 human colorectal carcinoma cells in vitro. The pro-oxidant and growth inhibitory effects of melatonin resulted in an accumulation of ROS and decreased antioxidant capacity in melatonin-treated cells. Ghrelin administration alone caused a significant decrease in the levels of ROS, due to an increased activity of CAT in the HCT 116 cells. In addition, the present study observed increased lipid peroxidation following melatonin treatment, and decreased levels of malondialdehyde following ghrelin or leptin treatment. In conclusion, ghrelin, leptin and melatonin have various influences on the antioxidant capacity of HCT 116 cells. Compared with the adipokines, treatment with melatonin increased ROS levels and decreased cellular viability.


Subject(s)
Antioxidants/metabolism , Ghrelin/pharmacology , Leptin/pharmacology , Melatonin/pharmacology , Reactive Oxygen Species/metabolism , Catalase/metabolism , Cell Survival/drug effects , Glutathione Peroxidase/metabolism , HCT116 Cells , Humans , Lipid Peroxidation/drug effects , Melatonin/antagonists & inhibitors , Oxidative Stress , Reactive Oxygen Species/agonists , Reactive Oxygen Species/antagonists & inhibitors , Superoxide Dismutase/metabolism
5.
Obes Surg ; 25(10): 1848-57, 2015 10.
Article in English | MEDLINE | ID: mdl-25697126

ABSTRACT

BACKGROUND: Ileal transposition surgery is an increasingly used procedure in combination with sleeve gastrectomy to control obesity and type 2 diabetes mellitus (T2DM). A short-term effect on glycemia amelioration after the ileal transposition (IT) procedure is observed; however, it appears that the effect is time dependent, and it remains uncertain if this effect is also linked with an adipose tissue hormonal activity. METHODS: Twenty male Zucker rats underwent IT or sham surgery. Six months after surgery, serum levels of adiponectin, vaspin, resistin, chemerin RBP4 were analyzed using ELISA kits. Tissue concentrations of glycogen sythase kinase alfa (GSK-3α), glucose 6-phosphatase (G6PC), glycogen phosphorylase (PYGM), and phosphofructokinase (PFK) in muscle and GLUT4 in visceral fat, white adipose tissue, and muscle were assessed in duplicate by an enzyme-linked immunosorbent assay (ELISA) kit. Additionally, the transposed ileum and analogical ileal segment of sham-operated rats were processed for histomorphometry analysis. RESULTS: The animals which underwent IT showed significantly a higher adiponectin and vaspin serum level. Concentrations of resistin decreased after IT surgery but were not significantly different between the groups. The plasma level of chemerin decreased significantly after IT and correlated negatively with adiponectin serum level in the IT group. The effects of IT on RBP4 serum level appeared to be significantly lower than those in the sham group and correlated with GLUT4 concentration in IT white adipose tissue negatively, but positively with the sham group. CONCLUSIONS: The data suggest that ileum transposition leads to a stimulatory effect on important adipokines involved in glucose metabolism. The adipokine serum level could be a useful biomarker of postoperative physiological state.


Subject(s)
Adipokines/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/surgery , Jejunoileal Bypass , Obesity, Morbid/surgery , Adipose Tissue, White/metabolism , Animals , Blood Glucose/metabolism , Body Weight , Gastrectomy/methods , Jejunoileal Bypass/methods , Male , Obesity, Morbid/blood , Postoperative Period , Rats , Rats, Transgenic , Rats, Zucker , Receptors, Leptin/genetics , Time Factors
6.
Pol J Pathol ; 65(3): 167-75, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25372413

ABSTRACT

Antioxidant enzymes (AOEs), including superoxide dismutase isoenzymes (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) along with glutathione reductase (GR), reduced glutathione (GSH) and glutathione transferase (GST), are thought to be necessary for life process in all oxygen-metabolizing cells by removing reactive oxygen species (ROS). The biological significance of AOEs in transformed cells is still unclear, but their capacity to survive may be affected by changes in cellular process such as proliferation, invasiveness, migration, apoptosis and drug resistance. This review summaries the significance of antioxidant enzymes in cancer cell progression mainly in an in vitro context.


Subject(s)
Antioxidants/metabolism , Neoplasms/enzymology , Oxidative Stress/physiology , Reactive Oxygen Species/metabolism , Animals , Disease Progression , Glutathione Peroxidase/metabolism , Glutathione Transferase/metabolism , Humans , Superoxide Dismutase/metabolism
7.
Biomed Res Int ; 2014: 517820, 2014.
Article in English | MEDLINE | ID: mdl-25121101

ABSTRACT

INTRODUCTION: Chemerin seems to be involved in pathogenesis of chronic hepatitis C (CHC). Hepatic expressions of chemerin and its receptor, chemokine receptor-like 1 (CMKLR1), in CHC have not been studied so far. AIM: To evaluate chemerin and CMKLR1 hepatic expression together with serum chemerin concentration in CHC patients and to assess their relationship with metabolic and histopathological abnormalities. METHODS: The study included 63 nonobese CHC patients. Transcription of chemerin and CMKLR1 was assessed by quantitative real-time PCR, while serum chemerin was assessed by enzyme-linked immunosorbent assay. RESULTS: Expression of chemerin and CMKLR1 was present in the liver of all CHC patients regardless of sex or age. This expression was not associated with necroinflammatory activity and steatosis grade, fibrosis stage, and metabolic abnormalities. There was a negative association between serum chemerin and chemerin hepatic expression (r = (-0.41), P = 0.006). CONCLUSION: The study for the first time confirmed a marked expression of chemerin and CMKLR1 in the liver of CHC patients. The study was performed using the homogenates of human liver tissue, so it is not possible to define whether hepatocytes or other cell types which are abundantly represented in the liver constitute the main source of chemerin and CMKLR1 mRNA.


Subject(s)
Chemokines/metabolism , Hepatitis C, Chronic/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Liver/metabolism , Receptors, Chemokine/metabolism , Body Mass Index , Case-Control Studies , Chemokines/blood , Female , Gene Expression Regulation , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/genetics , Hepatocytes/metabolism , Hepatocytes/pathology , Humans , Intercellular Signaling Peptides and Proteins/blood , Logistic Models , Male , Middle Aged
8.
World J Gastroenterol ; 20(22): 6912-7, 2014 Jun 14.
Article in English | MEDLINE | ID: mdl-24944482

ABSTRACT

AIM: To investigate serum adipokine levels in inflammatory bowel disease (IBD) patients before treatment and after achieving clinical remission. METHODS: Serum concentrations of six adipokines (tissue growth factor-ß1, adiponectin, leptin, chemerin, resistin, and visfatin) were studied in 40 subjects with active IBD [24 subjects with Crohn's disease (CD) and in 16 subjects with ulcerative colitis (UC)] before and after three months of therapy with corticosteroids and/or azathioprine. Clinical diagnoses were based on ileocolonoscopy, computed tomography or magnetic resonance enterography and histological examination of mucosal biopsies sampled during endoscopy. Serum levels of adipokines were assessed by an indirect enzyme-linked immunosorbent assay. The control group was comprised of 16 age- and sex-matched healthy volunteers. RESULTS: Baseline leptin concentrations were significantly decreased in both types of IBD compared to controls (8.0 ± 9.1 in CD and 8.6 ± 6.3 in UC vs 16.5 ± 10.1 ng/mL in controls; P < 0.05), and significantly increased after treatment only in subjects with CD (14.9 ± 15.1 ng/mL; P < 0.05). Baseline serum resistin concentrations were significantly higher in CD (19.3 ± 12.5 ng/mL; P < 0.05) and UC subjects (23.2 ± 11.0 ng/mL; P < 0.05) than in healthy controls (10.7 ± 1.1 ng/mL). Treatment induced a decrease in the serum resistin concentration only in UC subjects (14.5 ± 4.0 ng/mL; P < 0.05). Baseline serum concentrations of visfatin were significantly higher in subjects with CD (23.2 ± 3.2 ng/mL; P < 0.05) and UC (18.8 ± 5.3 ng/mL; P < 0.05) than in healthy controls (14.1 ± 5.3 ng/mL). Treatment induced a decrease in the serum visfatin concentrations only in CD subjects (20.4 ± 4.8 ng/mL; P < 0.05). Serum levels of adiponectin, chemerin and tissue growth factor-ß1 did not differ between CD and UC subjects compared to healthy controls and also were not altered by anti-inflammatory therapy. Clinical indices of IBD activity did not correlate with adipokine levels. CONCLUSION: IBD modulates serum adipokine levels by increasing resistin and visfatin release and suppressing leptin production.


Subject(s)
Adipokines/blood , Colitis, Ulcerative/blood , Crohn Disease/blood , Adrenal Cortex Hormones/therapeutic use , Adult , Anti-Inflammatory Agents/therapeutic use , Azathioprine/therapeutic use , Biopsy , Case-Control Studies , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/immunology , Colonoscopy , Crohn Disease/diagnosis , Crohn Disease/drug therapy , Crohn Disease/immunology , Cytokines/blood , Drug Therapy, Combination , Enzyme-Linked Immunosorbent Assay , Female , Gastrointestinal Agents/therapeutic use , Humans , Leptin/blood , Magnetic Resonance Imaging , Male , Middle Aged , Nicotinamide Phosphoribosyltransferase/blood , Resistin/blood , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
9.
BMC Surg ; 14: 20, 2014 Apr 11.
Article in English | MEDLINE | ID: mdl-24725654

ABSTRACT

BACKGROUND: Bariatric operations mostly combine a restrictive gastric component with a rerouting of the intestinal passage. The pylorus can thereby be alternatively preserved or excluded. With the aim of performing a "pylorus-preserving gastric bypass", we present early results of a proximal postpyloric loop duodeno-jejunostomy associated with a sleeve gastrectomy (LSG) compared to results of a parallel, but distal LSG with a loop duodeno-ileostomy as a two-step procedure. METHODS: 16 patients underwent either a two-step LSG with a distal loop duodeno-ileostomy (DIOS) as revisional bariatric surgery or a combined single step operation with a proximal duodeno-jejunostomy (DJOS). Total small intestinal length was determined to account for inter-individual differences. RESULTS: Mean operative time for the second-step of the DIOS operation was 121 min and 147 min for the combined DJOS operation. The overall intestinal length was 750.8 cm (range 600-900 cm) with a bypassed limb length of 235.7 cm in DJOS patients. The mean length of the common channel in DIOS patients measured 245.6 cm. Overall excess weight loss (%EWL) of the two-step DIOS procedure came to 38.31% and 49.60%, DJOS patients experienced an %EWL of 19.75% and 46.53% at 1 and 6 months, resp. No complication related to the duodeno-enterostomy occurred. CONCLUSIONS: Loop duodeno-enterosomies with sleeve gastrectomy can be safely performed and may open new alternatives in bariatric surgery with the possibility for inter-individual adaptation.


Subject(s)
Bariatric Surgery/methods , Duodenum/surgery , Gastrectomy/methods , Ileum/surgery , Jejunum/surgery , Obesity/surgery , Pylorus/surgery , Adult , Anastomosis, Surgical , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity, Morbid/surgery , Prospective Studies , Treatment Outcome , Weight Loss
10.
Eur J Pharmacol ; 732: 12-8, 2014 Jun 05.
Article in English | MEDLINE | ID: mdl-24681056

ABSTRACT

Haemorrhagic shock is a life threatening condition, and, as such, it is important to understand the mechanisms taking part in its reversal. In the 1990s, it was shown that activation of serotonin 1A receptors is responsible for the circulatory decompensation and development of the sympathoinhibitory phase. In previous reports, it was demonstrated that activation of serotonin 1A receptors induces resuscitative effects in haemorrhaged rats. However, the effectory mechanisms still require further investigation. The aim of the present study was to determine whether the sympathetic nervous system participates in the effects of serotonin through central serotonin 1A receptors in haemorrhagic shock in rats. In order to determine the role of the sympathetic nervous system alpha-1-, alpha-2-, and beta-adrenergic receptor agonists - prazosin, yohimbine and propranolol, respectively, were used. We found that stimulation of the central serotonin 1A receptors by the administration of a selective agonist - 8-hydroxy-2-(di-n-propylamino)tetralin, 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (8-OH-DPAT) into the lateral brain ventricle is connected with the activation of compensation mechanisms leading to the increase in the heart rate and blood pressure. The current results demonstrate that the stimulation of peripheral alpha-1-, alpha-2- and beta-adrenergic receptors plays an essential role in the resuscitative effect triggered by the stimulation of central serotonin 1A receptors.


Subject(s)
Receptor, Serotonin, 5-HT1A/physiology , Resuscitation , Serotonin Receptor Agonists/therapeutic use , Shock, Hemorrhagic/drug therapy , Shock, Hemorrhagic/physiopathology , Sympathetic Nervous System/physiopathology , 8-Hydroxy-2-(di-n-propylamino)tetralin/administration & dosage , 8-Hydroxy-2-(di-n-propylamino)tetralin/therapeutic use , Animals , Blood Pressure/drug effects , Heart Rate/drug effects , Injections, Intraventricular , Male , Rats , Rats, Wistar , Receptors, Adrenergic, alpha-1/drug effects , Receptors, Adrenergic, alpha-1/physiology , Receptors, Adrenergic, alpha-2/drug effects , Receptors, Adrenergic, alpha-2/physiology , Receptors, Adrenergic, beta/drug effects , Receptors, Adrenergic, beta/physiology , Serotonin Receptor Agonists/administration & dosage , Sympathetic Nervous System/drug effects , Vascular Resistance/drug effects , Vascular Resistance/physiology
11.
Surgery ; 155(1): 165-72, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24008091

ABSTRACT

INTRODUCTION: The possibility of achieving diabetes remission through bariatric surgery has dramatically changed treatment options for this disease. Ileal transposition (IT), specifically designed to provoke diabetes remission, has so far shown great success in rodent studies. However, it remains uncertain which combination of ileal length and origin produces best results. METHODS: Forty male Zucker rats underwent transposition of 25% distal, 50% distal, and 50% proximal ileum or sham surgery. Glucose control, insulin, and glucagon-like peptide (GLP)-1 serum levels were analyzed after 1, 3, and 6 months. Body weight was recorded weekly. RESULTS: In relation to sham-operated animals, the 50% distal IT presented with improved glucose tolerance after 1, 3, and 6 months (2-way analysis of variance [ANOVA]: P < .05, < .0001, and < .0001, respectively). The 25% distal and 50% proximal IT only showed improved glucose control after 3 months, suggesting a fading effect in long-term observation (2-way ANOVA: P < .0001 for both). Glucose-stimulated GLP-1 levels were steadily elevated only in the 2 distal IT groups (Mann-Whitney sham versus 50% distal, P < .01, < .01, and < .05; sham versus 25% distal, P < .01, = .001, < .05 for 1, 3, and 6 months, respectively). IT had no impact on serum insulin levels. CONCLUSION: The current study restates the findings of improved glucose tolerance and GLP-1 stimulation after IT, but is the first to demonstrate a fading glycemic effect in long-term observation. Systematic comparison of length and ileal origin revealed that long and distal transposition delivers best results.


Subject(s)
Bariatric Surgery/methods , Diabetes Mellitus, Experimental/surgery , Digestive System Surgical Procedures/methods , Ileum/surgery , Animals , Body Weight , Glucagon-Like Peptide 1/blood , Glucose Tolerance Test , Male , Obesity/complications , Obesity/surgery , Rats , Rats, Zucker
12.
Pestic Biochem Physiol ; 105(1): 5-12, 2013 Jan.
Article in English | MEDLINE | ID: mdl-24238283

ABSTRACT

In the present study we describe the effect of chloronicotinoid pesticide (imidacloprid) on the digestive enzymes activity of the Cameraria ohridella larvae after lasting 1 year sublethal exposure to imidacloprid pesticide. Caterpillars - L4 stage (fourth instar, hyperphagic tissue-feeding phase) - were collected from chemically protected white horse chestnut trees 1 year after imidacloprid treatment, and compared with caterpillars collected from non-treated trees in a previous study. Enzymes activity of α-amylase, disaccharidases, glycosidases and proteases was assayed. The presence of pesticide in ingested food changed the digestive enzymes profile of caterpillars. The analysis of correlations between different digestive enzymes showed many significant correlations (P<0.05) among glycolytic activities like ß-glucosidase and α-galactosidase activities. Statistically significant correlations for proteolytic activity were found between trypsin and chymotrypsin activity and aminopeptidase activity that occurred only in the 1st generation. PCA distinguished five primary components with eigenvalues higher than 1, from which the first two explain almost 59% of analyzed results. Surprisingly, in the pesticide treated groups significantly higher activities of sucrase and lactase in relation to control were found. In general, glycosidase (α-glucosidase, ß-glucosidase and ß-galactosidase) activities showed a similar pattern of activity in different generations. These results contrast with those obtained with control larvae, where significant differences in activities of α-glucosidase, ß-glucosidase and ß-galactosidase may result from the different quantity and quality food intake by subsequent generations of larvae. No inter-generation differences in total proteolytic activity were observed in treated larvae. The absolute value of total proteolytic activity was higher than that in the control group. The pesticide present in the vascular system of the horse chestnut tree significantly affected some of the digestive enzymes activities and - in consequence - also interrelationships between enzymes, what may affect the food digestion.


Subject(s)
Aesculus/parasitology , Imidazoles/pharmacology , Insect Proteins/metabolism , Larva/enzymology , Moths/drug effects , Nitro Compounds/pharmacology , Animals , Digestive System/enzymology , Larva/drug effects , Larva/growth & development , Moths/enzymology , Moths/growth & development , Neonicotinoids , alpha-Amylases/metabolism , alpha-Galactosidase/metabolism , alpha-Glucosidases/metabolism , beta-Galactosidase/metabolism
13.
Cell Biol Int ; 37(8): 835-42, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23554006

ABSTRACT

We have examined the role of melatonin receptor MT2 and quinone reductase II in the regulation of the redox status of preadipocytes (3T3-L1) in vitro. 3T3-L1 cells were treated with melatonin at a physiological concentration (10(-9) mol/L) and a supraphysiological (pharmacological) concentration (10(-3) mol/L) for 24 h. Luzindole (10(-4) mol/L), an antagonist of MT2 receptor, and prazosin (10(-5) mol/L), an inhibitor of quinone reductase II, were added 30 min before subsequent exposure of the cells to melatonin. The level of oxidative stress was determined by the analysis of activities of enzymes neutralising reactive oxygen species, and determination of the malondialdehyde (MDA) content. Melatonin increased activities of manganese and copper-zinc superoxide dismutase (MnSOD, Cu/ZnSOD) and catalase (CAT) at both a physiological concentration (10(-9) mol/L) and a pharmacological concentration (10(-3) mol/L). MDA content was unchanged, whereas activities of glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-Rd) were increased only by the physiological concentration. Both effects were partially inhibited by luzindole, but not prazosin. These observations suggest that melatonin, acting at least partially via MT2 receptors, can increase antioxidant enzymes activities in 3T3-L1 preadipocytes.


Subject(s)
Adipocytes/metabolism , Quinone Reductases/physiology , Receptor, Melatonin, MT2/physiology , 3T3-L1 Cells , Animals , Catalase/metabolism , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Malondialdehyde/metabolism , Melatonin/physiology , Mice , Oxidation-Reduction , Oxidative Stress , Prazosin/pharmacology , Quinone Reductases/antagonists & inhibitors , Receptor, Melatonin, MT2/antagonists & inhibitors , Superoxide Dismutase/metabolism , Tryptamines/pharmacology
14.
Oncol Rep ; 29(2): 771-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23232726

ABSTRACT

Visfatin has recently been established as a novel adipokine that is predominantly expressed in subcutaneous and visceral fat. Only few studies have investigated the effect of visfatin on prostate, breast, ovarian cancer as well as on astrocytoma cell biology. There have been no previous studies on antioxidative enzyme activities, proliferation processes or levels of DNA damage in malignant melanoma cells in response to visfatin stimulation. Here, we report that visfatin increases activity of selected antioxidative enzymes (SOD, CAT, GSH-Px) in culture supernatants of Me45 human malignant melanoma cells. Our findings suggest that visfatin triggers a redox adaptation response, leading to an upregulation of antioxidant capacity along with decreased levels of the lipid peroxidation process in Me45 melanoma cells. Moreover, visfatin led to a significantly increased proliferation rate in the study using the [(3)H]thymidine incorporation method. Unlike insulin, visfatin-induced melanoma cell proliferation is not mediated by an insulin receptor. Better understanding of the role of visfatin in melanoma redox states may provide sound insight into the association between obesity-related fat adipokines and the antioxidant defense system in vitro in melanoma progression.


Subject(s)
Adaptation, Physiological/drug effects , Cell Proliferation/drug effects , DNA Damage , Melanoma/enzymology , Nicotinamide Phosphoribosyltransferase/pharmacology , Oxidation-Reduction/drug effects , Analysis of Variance , Antioxidants , Catalase/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Glutathione Peroxidase/metabolism , Humans , Hydrogen Peroxide/pharmacology , Lipid Peroxidation/drug effects , Melanoma/genetics , Statistics, Nonparametric , Superoxide Dismutase/metabolism
15.
Scand J Gastroenterol ; 47(8-9): 1037-47, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22670657

ABSTRACT

INTRODUCTION: Fibroblast growth factor-21 (FGF21) regulates glucose, lipid, and energy homeostasis. Retinol-binding protein-4 (RBP4) controls metabolic and proliferative cell functions. AIMS AND METHODS: Aims of the study were to assess (1) serum FGF21 and RBP4 levels in 75 non-obese chronic hepatitis C (CHC) patients and 41 healthy controls similar in age and BMI; (2) the relationship between their serum concentration and insulin resistance, liver histology, and biochemical parameters; (3) their effectiveness as diagnostic markers. RESULTS: FGF21 levels increased significantly in CHC patients compared with controls (p = 0.04). CHC patients with steatosis had significantly higher FGF21 levels compared with those without steatosis (p = 0.01). FGF21 concentration was positively related to steatosis grade (r = 0.39, p = 0.007). RBP4 levels did not differ between CHC patients and controls, but were negatively associated with necro-inflammatory activity grade (r = (-0.34), p = 0.04), with significantly higher levels in patients with minimal inflammatory activity (G1 vs. G2/3, p < 0.001; G1 vs. G2, p = 0 < 001; G1 vs. G3, p = 0.01). After stepwise linear regression analysis adjusting for potential confounders, RBP4 levels retained their independent significance as a predictor of necro-inflammatory activity (ß = -0.31; t = -2.15, p = 0.035) and FGF21 levels as a predictor of steatosis (ß = 0.34; t = 2.31, p = 0.024). Serum FGF21 correlated with serum RBP4 levels (r = 0.32, p = 0.02). CONCLUSIONS: Serum FGF21 levels increased in CHC patients, especially in those with steatosis and were associated with steatosis grade. FGF21 seems to be a useful diagnostic marker in determining hepatic steatosis in CHC. A negative association between serum RBP4 and necro-inflammatory activity indicates that disease severity may determine RBP4 levels.


Subject(s)
Fatty Liver/blood , Fatty Liver/pathology , Fibroblast Growth Factors/blood , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/pathology , Retinol-Binding Proteins, Plasma/metabolism , Adult , Alanine Transaminase/blood , Biomarkers/blood , Body Mass Index , Case-Control Studies , Fatty Liver/complications , Female , Hepatitis C, Chronic/complications , Humans , Insulin Resistance , Linear Models , Male , Middle Aged , Multivariate Analysis , Statistics, Nonparametric
16.
Article in English | MEDLINE | ID: mdl-22702824

ABSTRACT

This study was undertaken to test the hypothesis that following exposure to insecticides, changes take place in the metabolism of carbohydrates and absorption in the midgut of insects. The Madagascar hissing cockroach (Gromphadorhina portentosa) was chosen for the experiment as a model organism, due to it being easy to breed and its relatively large alimentary tract, which was important when preparing the microperfusion midgut bioassay. In each group of cockroaches treated with imidacloprid and fenitrothion, absorption of glucose, expressed as the area under the curve (AUC), was elevated compared to the control group. Glucose in the hemolymph of the examined insects was present in a vestigial amount, often below the threshold of determination, so the determinable carbohydrate indices were: hemolymph trehalose concentration and fat body glycogen content. The level of trehalose found in the hemolymph of insects when exposed to fenitrothion, and irrespective of the level of concentration mixed into food, were significantly lower when comparing to the control samples. Imidacloprid acted analogically with one exception at the concentration of 10 mg·kg(-1) dry food where trehalose concentration did not differ from the control values. Coupling with fat body glycogen concentration was less visible and appeared only at the concentrations of 5 and 10 mg imidacloprid·kg(-1) dry food. As described in this study changes in the sugar distribution and midgut glucose absorption indicate that insects cover the increased energy needs induced by insecticides; also at the gastrointestinal tract level. The result indicates that the midgut glucose absorption parameters could be considered as a non-specific biomarker of insecticide toxicity.


Subject(s)
Cockroaches/drug effects , Fenitrothion/toxicity , Imidazoles/toxicity , Insecticides/toxicity , Nitro Compounds/toxicity , Absorption , Animals , Chromatography, Thin Layer , Cockroaches/metabolism , Dose-Response Relationship, Drug , Fat Body/drug effects , Fat Body/metabolism , Fenitrothion/administration & dosage , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/metabolism , Glucose/metabolism , Glycogen/metabolism , Hemolymph/drug effects , Hemolymph/metabolism , Imidazoles/administration & dosage , Insecticides/administration & dosage , Neonicotinoids , Nitro Compounds/administration & dosage , Trehalose/metabolism
17.
Bioelectromagnetics ; 33(8): 641-51, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22535669

ABSTRACT

The aim of this study was to assess the influence of cisplatin and an extremely low frequency electromagnetic field (ELF-EMF) on antioxidant enzyme activity and the lipid peroxidation ratio, as well as the level of DNA damage and reactive oxygen species (ROS) production in AT478 carcinoma cells. Cells were cultured for 24 and 72 h in culture medium with cisplatin. Additionally, the cells were irradiated with 50 Hz/1 mT ELF-EMF for 16 min using a solenoid as a source of the ELF-EMF. The amount of ROS, superoxide dismutase (SOD) isoenzyme activity, glutathione peroxidase (GSH-Px) activity, DNA damage, and malondialdehyde (MDA) levels were assessed. Cells that were exposed to cisplatin exhibited a significant increase in ROS and antioxidant enzyme activity. The addition of ELF-EMF exposure to cisplatin treatment resulted in decreased ROS levels and antioxidant enzyme activity. A significant reduction in MDA concentrations was observed in all of the study groups, with the greatest decrease associated with treatment by both cisplatin and ELF-EMF. Cisplatin induced the most severe DNA damage; however, when cells were also irradiated with ELF-EMF, less DNA damage occurred. Exposure to ELF-EMF alone resulted in an increase in DNA damage compared to control cells. ELF-EMF lessened the effects of oxidative stress and DNA damage that were induced by cisplatin; however, ELF-EMF alone was a mild oxidative stressor and DNA damage inducer. We speculate that ELF-EMF exerts differential effects depending on the exogenous conditions. This information may be of value for appraising the pathophysiologic consequences of exposure to ELF-EMF.


Subject(s)
Carcinoma, Squamous Cell/pathology , Cisplatin/pharmacology , Electromagnetic Fields/adverse effects , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Animals , Antioxidants/metabolism , Cell Line, Tumor , DNA Damage , Intracellular Space/drug effects , Intracellular Space/enzymology , Intracellular Space/metabolism , Intracellular Space/radiation effects , Lipid Peroxidation/drug effects , Lipid Peroxidation/radiation effects , Malondialdehyde/metabolism , Mice , Reactive Oxygen Species/metabolism , Time Factors
18.
Pol J Pathol ; 63(4): 213-20, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23359189

ABSTRACT

Vaspin was found to modulate insulin resistance (IR) and to inhibit proinflammatory and profibrogenic agents. The aim of the study was to evaluate vaspin serum concentration prior to and after antiviral treatment and to assess its relationship with morphological alterations, IR and response to antiviral therapy. The study encompassed 75 non-obese, non-diabetic chronic hepatitis C (CHC) patients, 30 of whom underwent antiviral treatment. Serum vaspin levels decreased in CHC patients and was positively associated with fibrosis stage (r = 0.44, p = 0.001). Serum vaspin was significantly higher in patients with septal fibrosis/cirrhosis or periportal fibrosis compared to those with portal fibrosis or without fibrosis (F3-4 vs. F2 vs. F1 vs. F0, p = 0.012). A marked increase in the serum vaspin level occurred in patients with periportal or more advanced fibrosis (F0-1 vs. F2-4, p < 0.001). Serum vaspin levels were also positively related to steatosis grade (r = 0.32, p = 0.03). Antiviral therapy did not change serum vaspin levels, irrespective of its efficiency. Our study showed that the serum vaspin level is decreased in CHC patients with non-advanced fibrosis, but the virus seems to have no direct effect on this finding. Progressive fibrosis is associated with rise of the vaspin level and this adipokine may serve as a predictor of advanced liver fibrosis.


Subject(s)
Hepatitis C, Chronic/blood , Hepatitis C, Chronic/pathology , Serpins/blood , Adult , Antiviral Agents/therapeutic use , Biomarkers/blood , Enzyme-Linked Immunosorbent Assay , Female , Hepatitis C, Chronic/drug therapy , Humans , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Male , Middle Aged , Young Adult
19.
Obes Facts ; 4(5): 386-92, 2011.
Article in English | MEDLINE | ID: mdl-22166759

ABSTRACT

AIM: Hypertension is a major health problem and is usually associated with common conditions such as obesity, which contribute to clinical cardiac dysfunction. The role of energy homeostasis hormones such as ghrelin and PYY 3-36 in cardiovascular function remains incompletely understood. Therefore, the aim of our study was to explore the potential differences in concentrations of ghrelin forms and PYY 3-36 circulating in obese patients with grade 1 and grade 2 hypertension, with higher and lower BMI and without and with insulin resistance as well as to determine whether these hormones may be associated with left ventricular hypertrophy. METHODS: A total of 142 adult subjects were studied in three subgroups: lean (BMI < 25 kg/m(2)) normotensive subjects and obese subjects (BMI 30.0-34.9 kg/m(2)), and obese subjects (BMI 35.0-39.9 kg/m(2)) under hypertensive treatment for at least 9 years. Fasting blood glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), lipid profile, urinic acid, acylated ghrelin (A-Ghr), total ghrelin (T-Ghr), and PYY 3-36 were measured. Insulin resistance was determined by the homeostasis model assessment of insulin resistance (HOMA-IR). We also echocardiographically assessed left ventricular mass (LVM) index (LVMI = LVM/height(2.7)). We evaluated the association between plasma T-Ghr, A-Ghr, PYY 3-36 levels with LVMI and other measured factors using univariate and multivariate analysis. RESULTS: There were significant differences between BMI, waist circumference (WC), LVMI, hs-CRP and A-Ghr/nonacylated ghrelin (NA-Ghr) ratio (in the two obese subgroups. There was no significant difference between T-Ghr, A-Ghr and PYY 3-36 levels between obese subgroups. T-Ghr and PYY 3-36 were significantly lower in obese patients than in the control group, whereas A-Ghr levels did not differ between obese and controls. A-Ghr/NA-Ghr ratio was significantly higher in patients with second-degree hypertension and BMI 35.0-39.9 kg/m(2) than in patients with first-degree hypertension and BMI 30.0-34.9 kg/m(2). There were negative associations between T-Ghr, NA-Ghr or PYY 3-36 and LVMI (r = -0.49, p = 0.0001; r = -0.47, p = 0.0001; or r = -0.18, p = 0.029, respectively) and positive association between A-Ghr/NA-Ghr ratio and LVMI (r = 0.3, p = 0.0003). T-Ghr and NA-Ghr, were associated negatively with fasting insulin (r = -0.31, p = 0.0025; and r = -0.36, p = 0.001, repectively), while A-Ghr/NA-Ghr ratio was positively associated with BMI and fasting insulin (r = 0.23, p = 0.041; r = 0.3, p = 0.0045, respectively). T-Ghr, A-Ghr, and NAGhr were also inversely related to HOMA-IR indices in obese patients (r = -0.43, p = 0.001; r = -0.32, p = 0.0359; r = -0.35, p = 0.001, respectively). In insulin-resistant obese subjects T-Ghr and NA-Ghr correlated negatively with HOMA-IR (r = -0.34, p = 0.0015; r = -0.28, p = 0.0116, respectively). LVMI was associated negatively with T-Ghr, NA-Ghr and PYY 3-36 (r = -0.49, p = 0.0001; r = -0.47, p = 0.0001; r = -0.18, p = 0.029, respectively). In addition, LVMI was positively associated with A-Ghr/NA-Ghr ratio (r = 0.30, p = 0.0003). CONCLUSION: Plasma ghrelin forms and PYY 3-36 levels are associated with LVMI. These associations indicate a possible interaction between gut peptides and the cardiovascular system in hypertension and obesity.


Subject(s)
Body Mass Index , Ghrelin/blood , Hypertension/complications , Hypertrophy, Left Ventricular/pathology , Insulin Resistance , Obesity/complications , Peptide YY/blood , Acylation , Adult , C-Reactive Protein/metabolism , Female , Heart Ventricles/pathology , Humans , Hypertension/blood , Hypertension/therapy , Insulin/blood , Male , Middle Aged , Multivariate Analysis , Obesity/blood , Reference Values , Waist Circumference
20.
Mol Med ; 17(11-12): 1397-410, 2011.
Article in English | MEDLINE | ID: mdl-21738955

ABSTRACT

Chronic hepatitis C (CHC) is generally a slowly progressive disease, but some factors associated with rapid progression have been identified. Steatosis, independently of its metabolic or viral origin, leads to liver injury and fibrosis. It is suggested that hepatitis C virus may contribute to a wide spectrum of metabolic disturbances-namely, steatosis, insulin resistance, increased prevalence of impaired glucose tolerance, type 2 diabetes mellitus and lipid metabolism abnormalities. Adipokines, which are produced mainly by adipose tissue, may influence the inflammatory response and insulin sensitivity and contribute to the development of metabolic abnormalities in CHC and also regulate fibrogenesis and angiogenesis. Visfatin was described as an adipokine with immunomodulating and proinflammatory properties that promotes B-cell maturation and enhances activation of leukocytes, synthesis of adhesion molecules and production of proinflammatory cytokines. Visfatin exerts insulin-mimetic effects, decreases plasma glucose levels and regulates cell energy balance. Chemerin stimulates chemotaxis of dendritic cells, macrophages and natural killer (NK) cells toward the site of inflammation. On the other hand, it inhibits synthesis of proinflammatory mediators and enhances adiponectin production, influences adipocyte differentiation and maturation and regulates glucose uptake in adipocytes. Vaspin expression in human adipose tissue seems to be a compensatory mechanism associated with obesity and insulin resistance. Vaspin suppresses leptin, tumor necrosis factor (TNF)-α and resistin expression. Leptin protects against liver steatosis but accelerates fibrosis progression and exacerbates the inflammatory process. In contrast, adiponectin exerts a hepatoprotective effect. In this report, data indicating a possible role of these adipokines in the pathogenesis of chronic hepatitis are summarized.


Subject(s)
Adiponectin/metabolism , Chemokines/metabolism , Hepatitis, Chronic/metabolism , Leptin/metabolism , Nicotinamide Phosphoribosyltransferase/metabolism , Serpins/metabolism , Humans , Intercellular Signaling Peptides and Proteins
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