ABSTRACT
In the current study, the protective effect of a mistletoe extract (Helixor®, HLX) on Itraconazole (ITZ)-induced hepatocellular injury and acute oxidative stress in rats was aimed to be investigated by histological, biochemical and comet assay methods. Four groups a control group, an HLX group (5mg/kg/14days/intraperitoneally (ip)), an ITZ group (100mg/kg/14days/oral) and an HLX plus ITZ group (5mg/kg/14days/ip+100mg/kg/14days/oral) were all created from 32 female Wistar albino rats. At the end of the experiment, AST and ALT liver enzymes, total oxidant status (TOS) levels and total antioxidant status (TAS) levels, histopathological analysis and comet assay were carried out. Highest genotoxicity, higher levels of plasma AST and ALT, higher TOS, more degeneration of liver histopathology including hepatocyte degeneration, hepatocyte apoptosis and necrosis, portal/periportal inflammation, bile ductus hyperplasia and multinuclear giant cell formation were observed in ITZ group (p<0.05). As opposed to that, administration of HLX plus ITZ improved histopathological changes and DNA damage and showed a dramatic decrease in AST, ALT and TOS levels (p<0.05) and an increase in TAS level (p<0.001) when compared to ITZ group. This study showed that the antioxidant properties of HLX administration significantly decreased acute oxidative stress and hepatocellular damage in rats given ITZ.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Mistletoe , Viscum album , Female , Animals , Rats , Antioxidants/pharmacology , Antioxidants/metabolism , Itraconazole/pharmacology , Viscum album/metabolism , Carcinoma, Hepatocellular/metabolism , Rats, Wistar , Liver Neoplasms/pathology , Oxidative Stress , Liver , Oxidants/pharmacology , Plant Extracts/pharmacology , Plant Extracts/metabolismABSTRACT
Chronic anemia, transfusion-associated iron deposition, and chelating agents lead to renal impairment in ß-thalassemia (ß-thal) patients. The present study aimed to determine the most reliable and practical method in assessing and predicting renal injury in ß-thal major (ß-TM) patients. Therefore, we assessed the predictive values of urine ß2-microglobulin (ß2-MG) and neutrophil gelatinase-associated lipocalin (NGAL) levels, their ratios to urine creatinine, and serum endocan level. Sixty ß-TM patients and 30 healthy controls were included. Renal functions of the patients and controls were evaluated by means of urine protein/creatinine ratio, urine ß2-MG, urine NGAL, and serum endocan level. The ß-TM and control groups were comparable in terms of the demographic characteristics. Of the ß-TM patients, 26.7% had glomerular hyperfiltration and 41.7% had proteinuria. Compared with the control group, the ß-TM group had significantly higher levels of urine protein/creatinine, urine ß2-MG, urine ß2-MG/creatinine, urine NGAL, urine NGAL/creatinine, and serum endocan. These parameters did not differ between the chelating agent subgroups in the patient group. Urine ß2-MG/creatinine and NGAL/creatinine ratios were the parameters with high specificity in predicting proteinuria. There were significant correlations of urine ß2-MG, urine NGAL, and serum endocan levels with serum ferritin concentration. Urine ß2-MG/creatinine, NGAL/creatinine, and protein/creatinine ratios were correlated with each other in the patient group. Positive correlations of urine ß2-MG, urine NGAL, and serum endocan levels with serum ferritin concentration indicated that iron deposition was associated with endothelial damage and renal injury.
Subject(s)
Biomarkers , Kidney Diseases/diagnosis , Kidney Diseases/metabolism , Lipocalin-2/metabolism , Neoplasm Proteins/metabolism , Proteoglycans/metabolism , beta 2-Microglobulin/metabolism , beta-Thalassemia/metabolism , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Disease Susceptibility , Female , Glomerular Filtration Rate , Humans , Iron Overload/diagnosis , Iron Overload/etiology , Iron Overload/metabolism , Kidney Diseases/etiology , Kidney Function Tests , Lipocalin-2/urine , Male , Middle Aged , Neoplasm Proteins/blood , Prognosis , Proteoglycans/blood , ROC Curve , Young Adult , beta 2-Microglobulin/urine , beta-Thalassemia/complications , beta-Thalassemia/therapyABSTRACT
BACKGROUND: Hip fracture is a common clinical problem which causes severe pain in geriatric patients. However, severe pain following fracture may bring on mental disorders and delirium. A neuroinflammatory response with IL-6 and IL-8 has been shown to be associated with the pathophysiology of delirium. In this study, our primary hypothesis is that preoperative femoral nerve block (FNB) intervention in geriatric patients will more effectively attenuate pain following trochanteric femur fracture than the preoperative paracetamol application. Our secondary hypothesis is that interleukin levels (IL-6, IL-8) in cerebrospinal fluid (CSF) will be lower in the femoral nerve block group than the paracetamol group. Our tertiary hypothesis is that the incidence of postoperative delirium will be lower in the femoral nerve block group. METHODS: The patients over 65 years of age with ASA status II-IV and admitted to the Emergency Service for femur fracture were included in this study. Recommendations of the 'delirium prevention table' were applied to all of the patients at arrival. In the first group, 15 mg/kg paracetamol was administered intravenously every eight hours. In the second group, femoral nerve blockage was performed, and a catheter was placed. Then, 0.5 mL/kg bupivacaine 0.25% was applied every eight hours. In both groups, pain scores four hours after interventions were recorded. All patients were operated within 48 hours under spinal anesthesia. During spinal anesthesia, 2 mL of CSF samples were taken from all patients for analysis of IL-6 and IL-8 cytokines, and pain scores during positioning were recorded. RESULTS: VAS scores four hours after the first preoperative pain treatment and during the positioning for regional anesthesia were significantly lower in the femoral nerve block group. IL-8 levels are significantly lower in the femoral nerve block group but not in IL-6 levels. The incidence of delirium was less in the femoral nerve block group, but the difference was not statistically significant. CONCLUSION: The femoral nerve block was more effective in preoperative pain management of trochanteric femur fracture and preventing pain during regional anesthesia application. The mean IL-8 level was lower in the femoral nerve block group when compared to the paracetamol group. There is no difference in the postoperative delirium incidence between groups.
Subject(s)
Delirium , Femoral Nerve/physiology , Hip Fractures/surgery , Nerve Block/methods , Pain Management/methods , Pain, Postoperative , Aged , Aged, 80 and over , Delirium/epidemiology , Delirium/etiology , Delirium/prevention & control , Female , Humans , Male , Pain, Postoperative/complications , Pain, Postoperative/drug therapyABSTRACT
AIM: In Parkinson's disease (PD), oxidative stress plays a substantial role in degeneration of dopaminergic neurons at the substantia nigra. Recent reports describe nesfatin-1 and glucagon-like peptide-1 (GLP-1) as molecules with neuroprotective property that relieve oxidative stress. In this study, we aimed to determine the blood levels of nesfatin-1, GLP-1 and oxidative stress status in patients with PD. MATERIAL AND METHOD: Forty patients with PD, followed-up at the Department of Neurology of Mugla Sitki Kocman University Training and Research Hospital, were enrolled, as well as 40 age- and sex-matched participants as a control group. We determined and compared nesfatin-1, GLP-1, total antioxidant status (TAS), and total oxidant status (TOS) levels in patients with PD and control group. RESULTS: The mean GLP-1 and nesfatin-1 values of patients with PD were lower than those of the control group, whereas their mean TOS value was higher. The mean TAS values, on the other hand, did not reveal any significant difference between the patient and the control groups. CONCLUSION: The lower nesfatin-1 and GLP-1 levels, in addition to higher TOS levels, in patients with PD compared to those of control group suggest that the neuroprotective effects of these molecules might be related to the oxidative processes. Further studies are required to search for the impact of abovenamed molecules on the treatment option and the likelihood that they may slow down disease progression.
Subject(s)
Glucagon-Like Peptide 1/blood , Nucleobindins/blood , Oxidative Stress/physiology , Parkinson Disease/blood , Aged , Aged, 80 and over , Female , Humans , Male , Middle AgedABSTRACT
INTRODUCTION Chronic obstructive pulmonary disease (COPD) is the most important lung disease leading to disability and even death. Recent studies have shown that the platelet indices are associated with several cardiovascular diseases; however, there is little data on COPD. OBJECTIVES We aimed to explore the relationship between platelet indices, together with the platelet-to-lymphocyte ratio (PLR), white blood cell count to mean platelet volume ratio (WMR), and red cell distribution width (RDW) and the severity of COPD. PATIENTS AND METHODS This retrospective study was based on data collected from a total of 153 COPD patients admitted to our outpatient clinic between March 2014 and March 2015. All of the participants underwent pulmonary function tests; FEV1, FVC, and FEV1/FVC were measured. The study population was divided into four according to the severity of COPD as group A (mild), group B (mild to moderate), group C (moderate to severe), and group D (severe). RESULTS A significant increase was found in platelet distribution width (PDW), MPV, plateletcrit, PLR, and RDW while WMR decreased as the COPD severity increases. In the multiple logistic regression analysis, we found that PDW and RDW were independently associated with the presence of severe COPD. ROC curve analysis showed that a PDW>14.85 was associated with severe COPD with 85% sensitivity and 86% specificity while RDW>14.45 was associated with severe COPD with 90% sensitivity and 87% specificity. CONCLUSIONS The PDW and the RDW are independently associated with disease severity, which may indicate hypoxemia, underlying inflammation, and oxidative stress in COPD.
ABSTRACT
Migraine is one of the most common types of pain associated with sterile inflammatory conditions. Soluble urokinase plasminogen activator receptor (suPAR) is a potential novel inflammatory marker. We aim to determine the association between serum values of suPAR, procalcitonin, fibrinogen, and high-sensitivity C-reactive protein (hs-CRP) and migraine disease characteristics. The study involved a total of 60 migraine patients (33 patients in the interictal period, 27 patients in the attack period) and 30 healthy individuals. The serum values of suPAR were found to be significantly higher in migraine patients in the attack period than in migraine patients in the interictal period, and in healthy individuals (p < .01 for both). In addition, levels of suPAR were determined to be higher in migraine with aura patients than in migraine without aura patients. When we subdivided migraine patients according to frequency of attack (attacks/month), significant differences were found between the suPAR and procalcitonin levels (measured during the attack period) of those in the frequent-attack group (4-5 or more) versus those in the less frequent attack group (less than 4). Serum levels of procalcitonin were shown to be significantly higher in migraine patients during the attack period compared with migraine patients in the interictal period and in control subjects (p = .001 for both). Significant differences were found between plasma levels of fibrinogen in migraine patients versus control subjects (p < .01). No statistically significant difference was found between levels of hs-CRP in migraine patients versus the control group. These findings may show that presenting a high level of suPAR in migraine patients with attack and aura results to predisposition to occurring on the symptoms and that high levels of suPAR, procalcitonin and fibrinogen in patients with migraine result in neurogenic inflammation during migraine headaches.
Subject(s)
Migraine Disorders/blood , Migraine with Aura/blood , Neurogenic Inflammation/blood , Receptors, Urokinase Plasminogen Activator/blood , C-Reactive Protein/metabolism , Calcitonin/blood , Female , Fibrinogen/metabolism , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Migraine Disorders/genetics , Migraine Disorders/physiopathology , Migraine with Aura/genetics , Migraine with Aura/physiopathology , Neurogenic Inflammation/genetics , Neurogenic Inflammation/physiopathology , Receptors, Urokinase Plasminogen Activator/geneticsABSTRACT
BACKGROUND: The protective effect of mistletoe extract (Helixor®, HLX) against methotrexate (MTX)-induced acute oxidative stress and nephrotoxicity in rats was evaluated by histological and biochemical methods as well as the comet assay. MATERIAL AND METHODS: 32 female Wistar albino rats were divided into 4 groups: control group, HLX group (5 mg/kg body weight (bw), days 1-10, intraperitoneally (i.p.)), MTX group (10 mg/kg bw, days 7, 8, and 9, i.p.), and MTX + HLX group (10 mg/kg bw, days 7, 8, and 9, i.p. + 5 mg/kg bw, days 1-10, i.p.). At the end of the experiment, the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), nitric oxide (NO), and myeloperoxidase (MPO) levels were measured, and a histopathological analysis and comet assay were carried out. RESULTS: MTX induced renal oxidative stress and nephrotoxicity in the rats. Pretreatment with HLX significantly improved the renal GSH-Px and SOD activities in the MTX + HLX group compared to the MTX group. The decrease in the NO and MPO levels in the rat groups pretreated with HLX was not significant. The histochemical evaluation revealed that HLX provided significant improvement in the MTX-induced renal degenerative changes, including tubule distension, interstitial inflammation, perirenal inflammation, glomerular congestion, glomerular degeneration, and parenchymal hemorrhage, in the MTX + HLX group compared to the MTX-administered group. According to the comet assay, pretreatment with HLX lowered the MTX-induced DNA damage in endogenous lymphocytes, although not significantly. CONCLUSION: This study demonstrated that HLX administration markedly reduced the MTX-induced acute oxidative stress and nephrotoxicity in rats through its antioxidant and anti-inflammatory properties.
Subject(s)
Kidney Diseases/therapy , Methotrexate/toxicity , Plant Extracts/therapeutic use , Viscum album/chemistry , Animals , DNA Damage/drug effects , Female , Kidney Diseases/prevention & control , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Rats , Rats, WistarABSTRACT
BACKGROUND: A limited number of human and animal studies suggest that a relationship exists between phthalates and obesity, although this is not supported by all research. The purpose of this study was to investigate the relationship between Body Mass Index (BMI) and the levels of phthalates in human blood and urine samples. METHODS: Sixty-four overweight or 132 obese individuals (total=196) of different ages (min-max, 17-62; mean ± SD, 42.07±11.3) and genders (F:M 97:99) enrolled in the study. BMI and waist circumference were measured to diagnose obesity. Venous blood samples were taken after overnight fasting. To compare the urine phthalates among participants, single spot urine (at least 10 mL) was collected from the subject after blood samples were taken. Urine and blood phthalate concentrations were measured using gas chromatography. RESULTS: Total blood/urinary phthalate levels significantly increased in proportion to the degree of obesity. There was a high correlation between the level of total phthalates in serum and BMI (ρ=0.697, P<0.001), and between total urinary phthalate levels and BMI (ρ=0.707, P<0.001). CONCLUSIONS: This is the first study to have shown that both blood and urinary phthalates increased in proportion to BMI. The results show a strong association between obesity and phthalates.
Subject(s)
Environmental Pollutants/blood , Environmental Pollutants/urine , Obesity/epidemiology , Phthalic Acids/blood , Phthalic Acids/urine , Adolescent , Adult , Body Mass Index , Female , Humans , Male , Middle Aged , Obesity/blood , Obesity/urine , Waist Circumference , Young AdultABSTRACT
OBJECTIVES: Walnuts contain numerous selected dietary factors that have an impact on brain functions, especially learning and memory formation in the hippocampus. Hippocampal N-methyl d-aspartate receptors (NMDARs) are involved in the formation of cognitive functions. In this study, we aimed to investigate the molecular effects of walnut supplementation on the hippocampal expressions of NMDARs involved in cognitive functions and lipid peroxidation levels in rats. METHODS: The male Sprague-Dawley rats (6 months old, n = 24) were fed with a walnut-supplemented diet (6% walnut diet, n = 12) and a control diet (rat food, n = 12) as ad libitum for 8 weeks. At the end of this period, NMDAR subunits NR2A and NR2B in the hippocampi were assayed by western blotting. Lipid peroxidation levels were measured using the thiobarbituric acid. RESULTS: The expression of NR2A and NR2B was elevated in the walnut-supplemented rats compared with the control group (P < 0.05). In addition, the levels of lipid peroxidation in the walnut-supplemented group were significantly decreased compared with the control group. DISCUSSION: We suggested that walnut supplementation may have protective effects against the decline of cognitive functions by regulating NMDAR and lipid peroxidation levels in the hippocampus. The study provides evidence that selected dietary factors (polyunsaturated fatty acids, melatonin, vitamin E, and flavonoids) within walnut may help to trigger hippocampal neuronal signal transduction for the formation of learning and memory.
Subject(s)
Functional Food , Hippocampus/metabolism , Juglans , Nuts , Receptors, N-Methyl-D-Aspartate/metabolism , Up-Regulation , Animals , Biomarkers/metabolism , Blotting, Western , Cognitive Dysfunction/prevention & control , Down-Regulation , Lipid Peroxidation , Male , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Neuroprotection , Random Allocation , Rats, Sprague-Dawley , Thiobarbiturates/metabolismABSTRACT
OBJECTIVE: We aimed to investigate the short-term effect of laparoscopic surgery on serum thiol-disulfide homeostasis levels as a marker of oxidant stress of surgical trauma in elective laparoscopic cholecystectomy patients. MATERIALS AND METHODS: Venous blood samples were collected, and levels of native thiols, total thiols, and disulfides were determined with a novel automated assay. Total antioxidant capacity (measured as the ferric-reducing ability of plasma) and serum ischemia modified albumin, expressed as absorbance units assayed by the albumin cobalt binding test, were determined. RESULTS: The major findings of the present study were that native thiol (283 ± 45 versus 241 ± 61 µmol/L), total thiol (313 ± 49 versus 263 ± 67 µmol/L), and disulfide (14.9 ± 4.6 versus 11.0 ± 6.1 µmol/L) levels were decreased significantly during operation and although they increased, they did not return to preoperation levels 24 hours after laparoscopic surgery compared to the levels at baseline. Disulfide/native thiol and disulfide/total thiol levels did not change during laparoscopic surgery. CONCLUSIONS: The decrease in plasma level of native and total thiol groups suggests impairment of the antioxidant capacity of plasma; however, the delicate balance between the different redox forms of thiols was maintained during surgery.
Subject(s)
Cholecystectomy, Laparoscopic , Disulfides/blood , Hernia, Inguinal/surgery , Herniorrhaphy , Oxidative Stress , Pneumoperitoneum, Artificial , Sulfhydryl Compounds/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Homeostasis , Humans , Male , Middle Aged , Oxidation-Reduction , Serum Albumin , Serum Albumin, Human , Young AdultABSTRACT
BACKGROUND: The level and activity of indoleamine 2,3-dioxygenase (IDO) and the concentrations of L-tryptophan and its metabolite L-kynurenine were determined in association with various renal diseases. However, there have been no data regarding these parameters in patients on peritoneal dialysis compared to those undergoing hemodialysis or kidney transplantation. METHODS: This study investigated the level and activity of IDO and determined oxidative balance by calculating the total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI). We enrolled 60 kidney disease patients, including 20 on peritoneal dialysis (PD group), 19 on hemodialysis (HD group), and 21 with kidney transplantation (KT group), as well as 21 control group. RESULTS: IDO levels were increased in the PD, HD, and KT groups compared to the control group. The concentration of kynurenine was significantly increased in the PD group compared to the other groups (p < 0.01). The kynurenine/tryptophan ratio was increased in the PD group compared to the other groups (all p < 0.01). TAS levels in the PD and HD groups were significantly decreased compared to the control group (both p < 0.05). TAS levels in the PD group were significantly decreased compared to the KT group. TOS levels in the PD group were higher than in the HD and KT groups. CONCLUSION: The results showed that IDO levels were increased in peritoneal dialysis and hemodialysis patients and in renal transplant recipients, while oxidative stress was found to be related to IDO activity and was most increased in the patients on peritoneal dialysis.
Subject(s)
Indoleamine-Pyrrole 2,3,-Dioxygenase/blood , Kidney Failure, Chronic/blood , Kynurenine/blood , Oxidative Stress , Tryptophan/blood , Adult , Case-Control Studies , Chromatography, High Pressure Liquid , Female , Humans , Kidney Failure, Chronic/therapy , Kidney Transplantation , Male , Middle Aged , Peritoneal Dialysis , Tandem Mass Spectrometry , TurkeyABSTRACT
This study investigates the preventive effect of caffeic acid phenethyl ester (CAPE) on pancreatic damage induced by vancomycin (VCM) in rats. Rats were equally divided into three groups: group I (control), group II (only VCM-treated group) and group III (VCM + CAPE-treated groups). VCM was intraperitoneally administered at a dose of 200 mg kg(-1)twice daily for 7 days. CAPE was administered orally at 10 µM mL(-1) kg(-1) dose once daily for 7 days. The first dose of CAPE administration was performed 24 h prior to VCM injection. Blood and pancreas tissue samples were removed and collected after the study. Serum alkaline phosphatase (ALP), amylase, γ-glutamyl transferase (GGT) and lipase activities were determined. Pancreas tissue samples were evaluated with the light microscope. Group II significantly increased serum ALP, amylase, GGT and lipase activities when compared with the control group. Group III significantly decreased serum ALP, amylase, GGT and lipase activities when compared with group II. In histopathological examination, it has been observed that there was a significant pancreatic damage in group II. CAPE exerted prominent structural protection against VCM-induced pancreatic damage and this effect was statistically significant. CAPE caused a marked reduction in the extent of pancreatic damage. We have concluded that it may play an important role in the VCM-induced pancreatic damage and reduce the pancreatic damage both at the biochemical and histopathological aspects.
Subject(s)
Caffeic Acids/pharmacology , Pancreas/drug effects , Phenylethyl Alcohol/analogs & derivatives , Vancomycin/adverse effects , Acute Disease , Alkaline Phosphatase/blood , Amylases/blood , Animals , Antioxidants/pharmacology , Lipase/blood , Male , Pancreas/pathology , Pancreatitis/chemically induced , Pancreatitis/drug therapy , Phenylethyl Alcohol/pharmacology , Rats , Rats, Wistar , Vancomycin/administration & dosage , gamma-Glutamyltransferase/bloodABSTRACT
Caffeic acid phenethyl ester (CAPE) has antioxidant and anti-inflammatory properties. The aim of this study is to examine the negative effects of toluene on kidney tissues and functions and to investigate the protective effects of CAPE against toluene-induced nephrotoxicity in rats. A total of 21 male Wistar rats were divided into three groups of equal number in each. The rats in group I were the controls. Toluene was intraperitoneally injected into the rats in group II with a dose of 500 mg/kg. Rats in group III received CAPE daily while exposed to toluene. After 14 days of experimental period, all rats were killed by decapitation. Enzymatic activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and malondialdehyde (MDA) levels were studied in the rat kidneys. Blood urea nitrogen (BUN) and serum creatinine levels were measured for renal function. The CAT and SOD enzyme activities and serum creatinine levels were significantly increased in rats treated with toluene when compared with the controls. But GSH-Px activity, MDA, and BUN levels showed statistically nonsignificant changes. However, increased CAT and SOD enzyme activities and decreased serum creatinine levels were detected in the rats that received CAPE while exposed to toluene. The GSH-Px activity and MDA and BUN levels in the same group did not show statistically significant changes. The results of our study demonstrated that toluene damages kidney tissue and is a nephrotoxic substance. CAPE was able to prevent the renal damage as antioxidant, antitoxic, and nephroprotective agent.
Subject(s)
Caffeic Acids/pharmacology , Kidney/drug effects , Phenylethyl Alcohol/analogs & derivatives , Protective Agents/pharmacology , Toluene/toxicity , Animals , Antioxidants/pharmacology , Blood Urea Nitrogen , Catalase/metabolism , Creatinine/blood , Dose-Response Relationship, Drug , Glutathione Peroxidase/metabolism , Kidney/pathology , Male , Malondialdehyde/metabolism , Phenylethyl Alcohol/pharmacology , Rats , Rats, Wistar , Superoxide Dismutase/metabolismABSTRACT
The aim of the present study was to assess the protective effect of silibinin against methotrexate (MTX)-induced pulmonary toxicity. Rats were divided into four groups (MTX, MTX + silibinin, silibinin and control. MTX was injected intraperitoneally (i.p) into female Wistar rats (10 mg/kg/day for 3 days), which resulted in significant increases in the serum levels of alanine aminotransferase, aspartate aminotransferase and oxidant enzymes, including nitric oxide and myeloperoxidase. Furthermore, significant reductions were detected in the serum activity levels of the antioxidative enzymes, glutathione peroxidase and superoxide dismutase, when compared with the control group. However, administration of silibinin (100 mg/kg/day for 10 days, i.p.) was shown to ameliorate the MTX-induced pulmonary toxicity, as indicated by the normalization of the oxidative stress parameters. Furthermore, silibinin treatment was demonstrated to reduce the histopathological changes associated with MTX. In conclusion, silibinin exhibited protective effects against MTX-induced pulmonary toxicity, which may be attributed to its antioxidant activity.
ABSTRACT
BACKGROUND: Diazinon (0,0-Diethyl 0-(1-6-methyl-2-isoprophyl 4 pyrimidinyl) phosphorothioate) (DI) is a very effective organophosphate pesticide, used widely in agriculture. Consequently, data on poisoning cases secondary to DI exposure are important. The DI may affect a variety of tissues, including liver. Silibinin is a pharmacologically active constitute of Silybum marianum, with documented antioxidant activity. OBJECTIVES: The aim of our study was to evaluate both histopathologically and biochemically whether silibinin is protective in DI induced liver damage. MATERIALS AND METHODS: Thirty two Wistar albino rats were divided into four groups, as follows: 1) control group - oral corn oil was given; 2) DI group - rats were administered orally 335 mg/kg in the corn oil solution; 3) Silibinin group - 100 mg/kg/day silibinin was given alone orally, every 24 hours for 7 days; 4) Silibinin + DI group - DI plus silibinin was given. All rats were sacrificed at the end of experiment. Superoxide dismutases (SOD), glutathione peroxidase (GPX), nitric oxide (NO) and myeloperoxidase (MPO) were investigated in serum and liver tissue. In addition, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activities were evaluated. The liver tissue was evaluated histopathologically with Hematoxilin & Eosin dye. RESULTS: Biochemically, ALT, AST, NO, MPO in serum and NO, MPO in liver tissue were found to be significantly higher in DI group, compared to control group (P < 0.001). In Group Silibinin + DI, serum AST, ALT, NO, MPO levels were significantly lower (P < 0.01), and both serum and tissue SOD activities were significantly higher, compared to DI group (P < 0.001). Diazinon induced histopathological changes in liver tissue were: severe sinusoidal dilatation, moderate disruption of the radial alignment of hepatocytes around the central vein, severe vacuolization in the hepatocyte cytoplasm, inflammation around central vein and portal region. In rats receiving both DI and silibinin, the DI induced changes accounted for less sinusoidal dilatation, vacuolization in the hepatocyte cytoplasm and the inflammation around central vein and portal region (P < 0.05). CONCLUSIONS: The DI was found to induce liver damage by oxidative stress mechanisms. Silibinin reduced the oxidative stress by inducing antioxidant mechanisms, thereby showing protective effect against DI induced liver damage. Further studies with silibinin should be performed regarding DI toxicity.
ABSTRACT
Itraconazole (ITZ) belongs to the triazole group of antifungals with potent keratinophilic and lipophilic features. Hepatotoxicity is one of its most remarkable features. Silibinin (SIL) is a plant used worldwide which is used in the treatment of many liver diseases and it is especially very well known for its hepatoprotective-cytoprotective effect. The aim of our study was to research the protective effect of SIL in ITZ-induced hepatotoxicity using biochemical and pathological tests. Liver enzymes and antioxidant enzyme activities were measured spectrophotometrically by using commercial kits. ALT and AST levels in ITZ group were significantly increased compared to the group, while the activities of GSH-Px and SOD had decreased (p < 0.05). When ITZ group was compared to ITZ + SIL group, AST, ALT, and levels of NO and MPO were significantly decreased, while the activities of GSH-Px and SOD were increased (p < 0.05). Histopathological evaluation showed that SIL significantly decreased periportal inflammation and parenchymal hepatocyte apoptosis in ITZ and ITZ + SIL groups (p < 0.05). Eventhough not statistically significant, partial improvement with the use of SIL has been detected (p > 0.05) in hepatocyte degeneration and multinuclear giant cell formation. According to the evaluation performed with comet assay method, ITZ leads to DNA damage, and the use of SIL significantly decreases DNA damage (p < 0.05). We have detected that the use of ITZ increases oxidative stress (MPO, NO), decreases antioxidant activity (SOD and GSH-Px), and leads to DNA damage and histopathological liver damage, whereas the use of SIL has a cytoprotective effect on the liver by increasing the antioxidant effect (SOD, GSH-Px) and by decreasing the oxidative stress (NO, MPO). ITZ causes the generation of ROS and leads to DNA damage and liver damage. SIL has a cytoprotective effect on the liver by increasing antioxidant enzyme activities, preventing the formation of ROS.
Subject(s)
Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Itraconazole/poisoning , Liver/metabolism , Reactive Oxygen Species/metabolism , Silymarin/administration & dosage , Animals , Antioxidants/administration & dosage , Chemical and Drug Induced Liver Injury/etiology , Cytoprotection/drug effects , Dose-Response Relationship, Drug , Drug Interactions , Female , Liver/drug effects , Oxidative Stress/drug effects , Rats , Rats, Wistar , Silybin , Treatment OutcomeABSTRACT
The aim of the study was to investigate serum 25-hydroxyvitamin D (25(OH) D3) levels in patients with vitiligo vulgaris in terms of causal relation and extension of the disorder. This study is a clinical cross-sectional study carried out in order to determine 25-hydroxyvitamin D levels among 25 patients with vitiligo vulgaris and in 41 controls. Fitzpatrick skin phototypes, history of autoimmune disease, family history of vitiligo, and duration of the disease were also evaluated. The mean levels of vitamin D in patient and the control group were 15.2±5.2 ng/dL and 14.4±6.2 ng/dL respectively (P>0.05). In our study, 48% of the patients had insufficient (<30 ng/mL) and 52% had very low (<15 ng/mL) levels of vitamin D. There was no correlation between age, duration of the disease, and body surface area affected with vitamin D levels. There was no significant difference in vitamin D levels between patients who had family history of vitiligo (5 patients, 20%) and those that did not. Vitamin D levels were found to be insufficient (<30 ng/mL) or very low (<15 ng/mL) in most of the patients with vitiligo vulgaris, but not statistically significantly different as a group when compared to the controls. More studies are needed to differentiate between the effects of low vitamin D levels on pathogenesis of vitiligo vulgaris and lower vitamin D levels as a result of the disease.
Subject(s)
Vitamin D Deficiency/blood , Vitiligo/blood , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Risk FactorsABSTRACT
OBJECTIVE: The aim of this study is to investigate the effects of caffeic acid phenethyl ester (CAPE) on isoproterenol (ISO)-induced myocardial injury in hypertensive rats. METHODS: Rats were divided into 4 groups (n=29): Control group (n=8), L-NNA (NG-Nitro-L-arginine) group (n=8), L-NNA+ISO (L-NNA+isoproterenol) group (n=7) and L-NNA+ISO+CAPE (L-NNA+ISO + caffeic acid phenethyl ester) group (n=6). ISO (150 mg/kg/day) was given intraperitoneally (i.p.) once a day for 2 consecutive days (at the 12th and 13th days of L-NNA treatment). NG-Nitro-L-arginine (L-NNA) was given orally (25 mg/kg/day) in drinking water for 14 days. CAPE (10 µmol/kg/day) was given (i.p.) for 7 days after the first week. Systolic blood pressure (SBP) was evaluated by the tail-cuff method and biochemical analysis were performed using an autoanalyzer and a spectrophotometer. RESULTS: SBP in all L-NNA-treated groups was found to be increased at seventh day. AST and LDH levels in LNNA+ISO group were significantly increased compared to control (AST: 125±5 vs. 105±2; LDH: 861±154 vs. 571±46 U/L respectively) (p<0.05). Also, ISO caused to extensive necrosis and mononuclear cell infiltration in hypertensive rat myocardium. CAPE application reversed the enhanced AST and LDH levels as well as the extensive necrosis and the mononuclear cell infiltration in LNNA+ISO+CAPE group compared LNNA+ISO. CONCLUSION: According to our findings, it might be suggested that CAPE may be a favorable agent to protect the hypertensive myocardium from the injury induced by isoproterenol via mechanisms such as the induction of the antioxidant enzymes and the inhibition of lipid peroxidation.
Subject(s)
Antioxidants/therapeutic use , Caffeic Acids/therapeutic use , Hypertension/drug therapy , Phenylethyl Alcohol/analogs & derivatives , Animals , Antioxidants/administration & dosage , Antioxidants/pharmacology , Blood Pressure/drug effects , Caffeic Acids/administration & dosage , Caffeic Acids/pharmacology , Disease Models, Animal , Injections, Intraperitoneal , Isoproterenol/adverse effects , Lipid Peroxidation , Myocardial Infarction/chemically induced , Phenylethyl Alcohol/administration & dosage , Phenylethyl Alcohol/pharmacology , Phenylethyl Alcohol/therapeutic use , RatsABSTRACT
BACKGROUND: The aim of this study was to analyze the role of the genetic variants of two synaptic vesicle proteins (VAMP2 and Synaptotagmin XI) and two presynaptic plasma membrane proteins (Syntaxin 1A and SNAP-25) in patients with idiopathic generalized epilepsy (IGE). METHOD: Eighty-five patients with IGE and 93 healthy subjects were included in the study. We analyzed the functional polymorphisms of VAMP2, Synaptotagmin XI, Syntaxin 1A and SNAP-25 genes with polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: In the patients with IGE, significant differences alleles and genotypes of 26 bp Ins/Del polymorphism of the VAMP2 gene and the 33-bp promoter region of Synaptotagmin XI were observed, however no associaton was found regarding Intron 7 rs1569061 of Syntaxin 1A gene, MnlI rs3746544 and DdeI rs1051312 polymorphisms of SNAP-25 gene compared with healthy subjects. Carriers of the C allele of Synaptotagmin XI had worse measures compared with the T allele of Synaptotagmin XI. In the haplotype analysis, the frequency of the T alleles of rs1569061 and of the C alleles of the 33-bp promoter region of Synaptotagmin XI was found to be significantly higher in patients with IGE as compared with the healthy subjects. CONCLUSION: The genetic variations of VAMP2, Synaptotagmin XI might be indication of the relationship between these genes and IGE.
Subject(s)
Epilepsy, Generalized/genetics , Synaptosomal-Associated Protein 25/genetics , Synaptotagmins/genetics , Syntaxin 1/genetics , Vesicle-Associated Membrane Protein 2/genetics , Adolescent , Adult , Epilepsy, Generalized/pathology , Female , Genetic Association Studies , Humans , Male , Synaptic Vesicles/genetics , Synaptic Vesicles/metabolismABSTRACT
Oxidative stress is accepted as a potential responsible mechanism in the pathogenesis of radiocontrast media (RCM)-induced hepatotoxicity. Therefore, we aimed to investigate the protective effects of ebselen against RCM-induced hepatotoxicity by measuring tissue oxidant/antioxidant parameters and histological changes in rats. Wistar albino rats were randomly separated into four groups consisting of eight rats per group. Normal saline was given to the rats in control group (group 1). RCM was given to the rats in group 2, and both RCM and ebselen were given to the rats in group 3. Only ebselen was given to the rats in group 4. Liver sections of the killed animals were analyzed to measure the levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as histopathological changes. In RCM group, SOD and CAT levels were found increased. In RCM-ebselen group, MDA, SOD and CAT levels were found decreased. In RCM-ebselen group, however, GSH-Px activities of liver tissue increased. All these results indicated that ebselen produced a protective mechanism against RCM-induced hepatotoxicity and took part in oxidative stress.