Radioprotective effects of melatonin and thymoquinone on liver, parotid gland, brain, and testis of rats exposed to total body irradiation.

BACKGROUND: This study aimed to investigate thymoquinone (TQ), and melatonin's radioprotective effects on liver, parotid gland, brain, and testis of rats which were exposed to total body irradiation (IR). METHODS: Thirty adult Wistar rats were randomly divided into four groups that are Group 1 (control group): total body IR only, Group 2: IR-Melatonin (10 mg/kg), Group 3: IR-TQ (10 mg/kg), and Group 4 (sham group): nothing. Total body IR dose was 6 Gy. Tissue samples were taken 90 min after IR. The measurements of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were performed in all groups. RESULTS: In IR group, GSH-Px and SOD activities significantly decreased whereas MDA levels significantly increased when compared with the sham in all tissues. We recorded a significant decrease in MDA levels in IR-TQ group in liver and parotid gland of rats. Moreover, SOD did not change in IR-TQ group compared with IR only group. DISCUSSION: Melatonin, a powerful antioxidant, plays role in preventing oxidative stress. We revealed that premedication with TQ significantly inhibited the increase in MDA induced by IR in liver and parotid gland and protected the activities of SOD, an antioxidant enzyme, in all other tissues. It has been revealed that TQ has a potential effect preventing IR-induced damage as much as melatonin.

Evaluation of Plasma Asymmetric Dimethylarginine Levels and Abdominal Aortic Intima-Media Thickness in Infants of Smoker Mothers.

OBJECTIVE: Smoking during pregnancy has harmful effects on the fetus and infant. Although some studies suggest that exposure to fetal-maternal smoking adversely affects both fetal growth and cardiovascular development, the mechanisms and biochemical consequences of smoking in pregnancy and newborns are not yet fully understood. We aimed to investigate whether maternal smoking during pregnancy causes fetal cardiovascular effect by measuring serum asymmetric dimethylarginine (ADMA) level and abdominal aortic intima-media thickness (aIMT). STUDY DESIGN: This prospective study was conducted in newborns of smoking mothers and never-smoker control mothers during their pregnancies. The babies were evaluated echocardiographically on the first day following birth. In two-dimensional mode, abdominal aIMT measurements were performed. ADMA was measured in umbilical cord blood at birth. RESULTS: There were 25 mothers in the study group and 25 mothers in the control group. Serum ADMA levels were 0.459 ± 0.119 µmol/L in the study group and 0.374 ± 0.1127 µmol/L in the control group (p = 0.034). The aIMT value in the study group was 0.84 ± 0.026 mm and the aIMT value in the control group was 0.63 ± 0.011 mm (p = 0.005). CONCLUSION: We found that both the serum ADMA and the aIMT significantly increased in the group with newborns of smoker mothers compared with the group of the newborns of never-smoker mothers. It may also be suggested that exposure to fetal-maternal smoking adversely affects cardiovascular development. KEY POINTS: · It is a known fact that smoking during pregnancy has harmful effects on the development of the fetus and infant.. · We found that both the serum ADMA and aIMT were significantly higher in the group of infants of smoker mothers..

Association of adverse outcomes of intrahepatic cholestasis of pregnancy with zonulin levels.

Our aim was to investigate serum zonulin levels in intrahepatic cholestasis of pregnancy (ICP) and to determine the usefulness of zonulin in ICP follow-up. A prospective case-control study was carried out which included 88 pregnant women (44 patients with ICP and 44 controls). Maternal serum samples obtained from all participants and zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Compared with controls, women with ICP had significantly higher zonulin levels (mean 0.728 ± 0.520 ng/mL vs. 1.303 ± 0.63 ng/mL, p <.001). According to the receiver operating characteristic (ROC) analysis performed for the predictive value of zonulin levels for ICP, the area under the curve (AUC) was 0.761 (95% CI: 0.661-0.860). Multivariable logistic regression analysis revealed serum zonulin levels was independently associated with adverse perinatal outcomes (OR = 1.278, 95% CI: 0.232-7.041), severity ICP (OR: 7.535, 95% CI: 1.597-13.553) and also unresponsiveness to treatment in ICP (OR: 4.178, 95% CI: 0.929-8.784).IMPACT STATEMENTWhat is already known on this subject? Zonulin is a regulator protein that increases the intestinal permeability by modulating the intercellular tight junctions (TJ). It is the only physiological protein known to control intestinal permeability and damage of the intestinal barrier is one of the causes of absorption disorders, inflammation and autoimmunity. ICP is a relatively non-threatening condition to women but is linked with a higher risk of preterm delivery, foetal distress and foetal death.What do the results of this study add? This study showed that increased levels of zonulin are associated with adverse perinatal outcomes, severity of ICP and unresponsiveness to treatment in ICP.What are the implications of these findings for clinical practice and/or further research? Focussing on preservation of intestinal permeability may be an alternative preventive strategy to reduce the adverse perinatal outcomes and severity of ICP. Further longitudinal studies are needed to verify the relationships among zonulin levels and pregnancy-related diseases.

Dynamic thiol/disulfide homeostasis as a novel indicator of oxidative stress in patients with urolithiasis.

Purpose: A dynamic thiol/disulfide balance is pivotal in organizing anti-oxidant defense, detoxification, apoptosis, and enzyme activities, as well as transcription and cellular signal-transfer mechanisms. The connection between urolithiasis and oxidant/antioxidant status, which can be assessed through thiol-disulfide homeostasis (TDH), has not yet been examined. In this study, we evaluated the effects of TDH on the formation, size, and location of stones by examining the associations between TDH parameters and urolithiasis. Materials and Methods: Patients with urolithiasis and healthy controls were recruited. The patients were divided into subgroups in terms of stone size (>15 mm or ≤15 mm) and stone location (nephrolithiasis or ureterolithiasis). TDH parameters were measured using a novel automatic and spectrophotometric method and compared statistically. Results: TDH parameters were different between the urolithiasis and control groups. TDH tended towards the disulfide side in the urolithiasis group. Stone size increased an average 0.14 mm with a 1 µmol/L increase in disulfide level and decreased an average 0.058 mm with a 1 µmol/L increase in native thiol level. Disulfide and native thiol levels were found to be different across patients with stone size >15 mm, ≤15 mm, and controls (p<0.001 and p<0.001, respectively). However, the nephrolithiasis and ureterolithiasis groups were similar in respect of TDH parameters. Conclusions: In this study, it was found that patients with urolithiasis displayed oxidative stress characterized by a TDH tendency towards the disulfide side, and an inadequate antioxidant response identified by a lower level of native thiol as compared with healthy controls.

Associations between night eating syndrome and metabolic parameters in pregnant women.

OBJECTIVE: In this study, we aimed to evaluate the incidence of night eating in pregnancy and the relationship between night eating scores and nutritional status, insulin resistance, and lipid profile in pregnant women. MATERIALS AND METHODS: In this study, 148 pregnant women who presented to the Gynecology and Obstetrics Clinics at Konya Training and Research Hospital in Konya were divided into two groups according to their night eating scores. These two groups were compared in terms of their nutritional attitudes and metabolic parameters. RESULTS: Comparisons of participants meeting night eating syndrome (NES) scores versus women without NES indicated that patients with NES exhibited fever hunger at breakfast time, more breakfast skipping (p<0.05) than those without NES. Also homeostatic model assessment insulin resistance, insulin, and high-density lipoprotein cholesterol parameters were significantly higher in pregnant women in the NES group (p<0.05). Also, correlations were found between higher night eating questionnaire total scores and higher HbA1c, insulin resistance, insulin, and more breakfast skipping. CONCLUSION: The results of this study suggest that night eating symptoms during pregnancy may increase and this is able to effect glucose metabolism.

Evaluation of cardiovascular risk by growth-differentiation factor-15 and tissue Doppler imaging in children with subclinical hypothyroidism.

OBJECTIVE: Subclinical hypothyroidism, defined as increased TSH serum levels and normal serum free T4 concentrations, has been associated with an increased risk of heart disease in adults. But, data in children and adolescents are scanty and treatment of subclinical hypothyroidism is controversial. Growth differentiation factor-15 (GDF-15) is a promising biomarker of cardiac remodeling. This study aimed to evaluate the cardiovascular risk factors in children with subclinical hypothyroidism, measured with tissue Doppler echocardiography (TDE), and conventional echocardiography and GDF-15 level. METHODS: The study comprised a total of 41 pediatric patients with subclinical hypothyroidism (SH) (mean age 9.6 ± 4.7 years) and 31 healthy children (mean age 11.2 ± 3.4 years) as the control group. Subclinical hypothyroidism was defined as a thyroid-stimulating hormone level higher than 4 mIU/l and a normal free-thyroxine level (0.6-1.8 ng/dl). Tissue Doppler echocardiography was performed to all individuals in the control group and patient group at the beginning of the study. Global systolic function as assessed by left ventricular ejection fraction was compared between groups. The serum GDF-15 level was measured. RESULTS: There were no significant differences in demographic parameters between the SH and control groups. The left ventricular internal diameter end systole, interventricular septal end diastole, left ventricular posterior wall end diastole, and tricuspid annular plane systolic excursion values were significantly different between the SH and control groups (p = 0.038, 0.028, 0.005, and 0.000, respectively). The mean mitral isovolumic relaxation time value of the SH group was 57.2 ± 9.3 ms, compared to 44.5 ± 5.6 ms for the control group (p = 0.000). The mean tricuspid isovolumic contraction time value of the SH group was 58.7 ± 9.4 ms, and that of the control group was 45.1 ± 5.3 ms (p = 0.000). The mean tricuspid isovolumic relaxation time value of the SH group was 58.03 ± 9.5 ms, and that of the control group was 45.1 ± 5.3 ms (p = 0.000). There were no significant differences in the other m-mode or pulse Doppler echocardiography values between two groups. The GDF-15 value of the SH group was 382.6 ± 268.2 pg/mL, and that of the control group was 473.6 ± 337.9 pg/mL; this difference was not significant. CONCLUSION: Patients with subclinical hypothyroidism versus healthy individuals had some changes in echocardiographic parameters that indicate involvement of diastolic function of the left ventricle. They were significantly different when compared SH group and the control group. This study demonstrated ventricle diastolic dysfunction in pediatric patients with hypothyroidism. The results of our study suggest that cardiac follow-up may be useful in patients with subclinical hypothyroidism and clinical trials are needed to explore therapeutic effects of T4 and T3 administration in this patients.

Evaluation of the radioprotective effects of thymoquinone on dynamic thiol-disulphide homeostasis during total-body irradiation in rats.

Ionizing radiation-induced free radicals cause functional and structural harmful effects. Thiol, an important antioxidant, plays a major role in the eradication of reactive oxygen molecules. Thiol/disulphide homeostasis is a marker of oxidative stress. The objective of this study was to assess the potential radioprotective effects of thymoquinone (TQ) on the dynamic thiol/disulphide homeostasis of rats receiving total-body irradiation (IR). Twenty-two rats were divided into three groups to test the radioprotective effectiveness of TQ. The sham control group did not receive TQ or IR. The IR group received only total-body IR. The TQ + IR group received IR plus TQ. Following IR, blood samples were taken. The thiol/disulphide homeostasis parameters were analysed by a newly established method. In the IR group, native thiol and the native thiol/total thiol ratio were significantly decreased (P = 0.003 and P = 0.003, respectively), whereas the disulphide/native thiol and disulphide/total thiol ratios were significantly increased when compared with those of the sham control group (P = 0.003 and P = 0.003, respectively). In the TQ + IR group, the mean disulphide, native thiol and total thiol levels and the disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were not found to be significantly different when compared with those of the sham control group (P > 0.05 for all). Thiol/disulphide homeostasis was found to be disturbed after IR exposure. The results showed that TQ had antioxidant effects and reduced the IR-induced oxidative stress, which was demonstrated through the dynamic thiol/disulphide homeostasis. Thus, the use of TQ before radiation treatment helped protect the rats from oxidant side effects.

Prognostic value of interferon-gamma, interleukin-6, and tumor necrosis factor-alpha in the radiation response of patients diagnosed with locally advanced non-small-cell lung cancer and glioblastoma multiforme

Background/aim: This study aimed to investigate the effect of chemoradiotherapy (CRT) on interferon-gamma (IFN-γ), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), which are critical markers of the clinical radiation response of patients with locally advanced non-small-cell lung cancer (NSCLC) and glioblastoma multiforme (GBM). Materials and methods: Thirty patients who were treated with CRT and 20 healthy controls were prospectively evaluated. Circulating levels of cytokines were measured by enzyme-linked immunosorbent assay procedure. Post-CRT and pre-CRT levels were compared. Results: Post-CRT, TNF-α and IFN-γ levels were significantly lower than pre-CRT levels in the NSCLC and GBM groups, respectively. The statistical analysis did not show any significant difference between the post- and pre-CRT IL-6 levels. However, the pre-CRT IL-6 levels in the GBM group and post-CRT IL-6 levels in the NSCLC group were significantly higher than those of the control group. Conclusion: CRT affected TNF-α levels in NSCLC and IFN-γ levels in GBM, with the levels of both decreasing significantly. The IL-6 levels of the post-CRT NSCLC group were higher than those of the post-CRT GBM group. Irradiation-induced IL-6 may be responsible for tumor regrowth. Therefore, treatment with IL-6 inhibitors could be a potential therapeutic strategy for sensitizing NSCLC to irradiation in the clinic.

Dynamic thiol disulphide homeostasis in operating theater personnel exposed to anesthetic gases.

BACKGROUND: The purpose of this study was to investigate the association between dynamic thiol/disulphide homeostasis and occupational exposure to volatile anesthetic gases in operating theater personnel. Decreased blood thiol levels and raised blood disulphide levels serve as biomarkers of oxidative stress. METHODS: We included 65 subjects occupationally exposed and 55 unexposed healthy medical professionals into the study. A novel method enabled separate measurements of components involved in dynamic thiol/disulphide homeostasis (native thiol, disulphide, and total thiol). To control for the potential confounding effect on oxidative stress of psychological symptoms potentially caused by occupational stress, we used scores obtained from four different anxiety and depression inventories. RESULTS: Mean ± standard deviation native thiol was found to be 433.35 ± 30.68 in the exposed group, lower than among controls, 446.61 ± 27.8 (P = 0.02). Disulphide in the exposed group was 15.78 ± 5.12, higher than among controls, 12.14 ± 5.33 (P < 0.001). After adjusting for anxiety and depression scores, age and gender, native thiol remained lower and disulphide higher in the exposed group (P = 0.008 and P < 0.001). CONCLUSION: Dynamic thiol/disulphide homeostasis in workers exposed to anesthetic gases was found to be disturbed after adjusting for the possible contribution of anxiety. We infer that this is due to the oxidative effect of exposure to anesthetic gases.