The Effect of Thymoquinone on Oxidative Stress Parameters and Apolipoprotein E in Alzheimer Model in Rats.

INTRODUCTION: In this study, it was aimed to investigate the effect of thymoquinone (TQ) on oxidative stress and apolipoprotein E (ApoE) in an experimental Alzheimer's model created with AlCl3 and D-galactose in rats. METHODS: Thirty-six Wistar Albino male rats saline group (Group 1), aluminum chloride (AlCl3) + D-galactose (D-Gal) group (Group 2), AlCl3 + D-Gal + TQ group (Group 3) were divided into 3 groups. The study was completed with 33 rats. Group 1 was given saline intraperitoneally (i.p) for 28 days. 2nd group; D-Gal at a dose of 60 mg/kg/day and AlCl3 at a dose of 40 mg/kg/day were given i.p. daily for 28 days. 3rd group; D-Gal at a dose of 60 mg/kg/day and AlCl3 at a dose of 40 mg/kg/day were given i.p. daily for 28 days. Group 3 rats were given 20 mg/kg/day TQ in corn oil by gavage for 14 days. Malonyl dialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAS), total oxidant capacity (TOS), glutathione peroxidase (GsH-Px), and ApoE levels were determined in the blood and brain tissues of rats in all three groups. One-way ANOVA test was used in the statistical analysis of the data. RESULTS: Means of TAS, TOS, GSH-Px, SOD, MDA, and ApoE in blood and brain tissue of all three groups (excluding ApoE in brain tissue) were different from each other and this difference was statistically significant (p < 0.05). CONCLUSION: In this study, TQ, it was determined that all oxidative stress parameters examined had positively affected and decreased blood tissue ApoE levels. TQ can be used as an antioxidant and curative in Alzheimer's disease.

The Effect of Mesenchymal Stromal Cells on the Mortality of Patients with Sepsis and Septic Shock: A Promising Therapy.

Purpose: Sepsis and septic shock are the major causes of death in intensive care units. This study aimed to evaluate the clinical safety and efficacy of mesenchymal stem cells (MSCs) in sepsis and septic shock patients. Methods: Ten patients were enrolled in the study. Adipose-derived MSC infusions were given (1 × 106/kg, on the 1st, 3rd, 5th, 7th, and 9th days of therapy) together with standard therapy. Before the MSC applications, blood samples were collected for cytokine assessment (TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10). The clinical and laboratory improvements were recorded and compared with control groups selected retrospectively. The clinical trial was registered on 16.03.2022 with the registration number NCT05283317. Results: In the study group, the ages of patients ranged from 22 to 68 years, and APACHE II scores ranged from 14 to 42. In the control group, ages ranged from 22 to 80 years and their APACHE II scores were between 14-35. The survival rate in the study group was 100% on the 14th day whereas it was 70% on the 28th day. A significant decrease in the SOFA score (adjusted), clinical, and laboratory improvements were observed during the MSC administration. However, no significant cytokine level changes were observed. In the control group, the survival rate of 20 patients was 70% on the 14th day, whereas 60% was on the 28th day. While deaths were observed in the control group in the first week of treatment, deaths in the MSCs group were observed between the 15th and 28th days. Conclusion: MSCs treatment may have a positive impact on the survival rates of sepsis during the early phase. However, further randomized controlled studies with a large group of patients are needed. Trial Registration. This trial is registered with ClinicalTrials.gov Identifier: NCT05283317.

Flow cytometric analysis of platelet surface glycoproteins in the diagnosis of thirty-two Turkish patients with Glanzmann thrombasthenia: a multicenter experience

Background/aim: Glanzmann thrombasthenia (GT) is a rare autosomal recessively inherited bleeding disorder characterized by the quantitative (type 1 and type 2) or qualitative (type 3) deficiency in platelet membrane glycoprotein (GP) IIb/IIIa (CD41a/CD61) fibrinogen receptors. In type 1, 2, and 3, CD41a/CD61 expression is 5%, 5%­20% and above 20%, respectively. In this study, diagnosis of GT was confirmed and subgroups were identified in 32 Turkish patients by flow cytometry analysis. Materials and methods: CD41a/CD61 expression levels in platelet-rich plasma (PRP) obtained from peripheral venous EDTA blood samples were analyzed with a BD FACSCanto II flow cytometer (Becton Dickinson, Franklin Lakes, NJ, USA). GT subgroup analysis was performed by counting 50,000 events in the BD FACSDiva Software v6.1.3 program of the instrument. Results: In the present study, in blood samples of 32 patients from 23 families with GT and 22 healthy controls, co-expression levels of CD41a and CD61 in PRP was analyzed. 12 out of 23 families were consistent with type 1 GT (52.2%), 4 were consistent with type 2 GT (17.4%), and 7 were consistent with type 3 GT (30.4%). Conclusion: Especially due to consanguineous marriages, GT with various glycoprotein levels may be detected. As a result of the flow cytometry analysis of the present study with the highest GT patient population in Turkey, type 1 GT patients were the most common subgroup. In the determination of the GT subgroups; especially in the detection of type 3 GT, flow cytometry is the most sensitive glycoprotein analysis method. In addition to light transmission aggregometry, CD41a/CD61 study by flow cytometer confirms diagnosis when mutation analysis cannot be performed.

Melatonin Supplementation Ameliorates Energy Charge and Oxidative Stress Induced by Acute Exercise in Rat Heart Tissue.

BACKGROUND: Regular physical exercises may help people to be more resistant to everyday problems; however, how acute and intense exercises affect the heart tissues functioning with maximum capacity and how melatonin changes the effect of acute and intense exercises are still not obvious. We aimed to comprehend whether melatonin intravenous injection supports the oxidative/antioxidative conditions and energy charge in heart tissues of rats exposed to acute swimming exercise. METHODS: Thirty Wistar-albino male rats were categorized into 3 groups with equal number of subjects. Control group performed no application, and acute intensive swimming exercise group were subjected to acute intensive swimming exercise for 30 minutes, and melatonin group were applied 25 mg/kg single dose melatonin administration prior to 30 minutes acute intensive swimming exercise. The levels of malondialdehyde (MDA), and superoxide dismutase, catalase and glutathione peroxidase activities were measured by spectrophotometric method; and the levels of 3-nitrotyrosine (3-NT) and energy charge were determined by a high performance liquid chromatography. RESULTS: Tissue MDA and 3-NT levels of the acute intensive exercise group were found to be higher than the control group. It was also found that the melatonin administration increased the energy charge and antioxidant activities, while decreased tissue MDA and 3-NT levels in heart tissues. Our results provide evidence for melatonin that can exert potent protective effects on oxidative stress and energy charge for heart tissues in acute swimming exercise. CONCLUSIONS: These findings suggest that the direct beneficial effects of melatonin could be potentially applied on prevention of oxidative stress and energy deficit.

Long-term efficacy of lipoprotein apheresis in the management of familial hypercholesterolaemia: Application of two different apheresis techniques in childhood.

Lipoprotein apheresis is used to treat patients with familial hypercholesterolemia (FH). The aim of the present study is to clarify the lipoprotein apheresis procedure performed by cascade filtration (CF) or double filtration plasmapheresis (DFPP) on pediatric patients in terms of side effects, laboratory results and cardiovascular follow-up. Data of ten pediatric patients were analyzed retrospectively. The average age of the patients was 12.1 ± 3.4 years. Percentage of long term reduction of low density lipoprotein cholesterol was 62.35 ± 7.19% (n = 3) for CF and 63.66 ± 6.63% (n = 3) for CF plus DFPP, 64.79 ± 8.29% (n = 7) for DFPP. Cardiovascular disease was not detected in thirty percent of the patients. Lesions remained stable in fifty percent of patients with heart valve lesions. Valvular lesions worsened in twenty percent of patients. Lipoprotein apheresis can be used effectively and successfully in pediatric patients as well as adults for homozygous FH.

Evaluation of peripheral blood CD34+ cell count in the acute phase of traumatic brain injury and chest trauma.

AIM: To determine the impact of traumatic brain injury (TBI) and chest trauma (CT) on the number of peripheral blood (PB) stem cells in affected patients in comparison to normal controls. Additionally, the aim was to determine the relationship between CD34+ cell counts and TBI-induced hypothalamus-pituitary-adrenal axis dysfunction in the acute phase of trauma. PATIENTS AND METHOD: Thirty patients with TBI, 12 patients with CT and 53 healthy subjects were included in the study. RESULTS: CD34+ cell counts within the first 24-48 hours of TBI were found to be lower than those obtained on the 7(th) day of TBI and those in the healthy controls. CD34+ cell counts obtained on the 2(nd) day of CT were lower than those in the healthy group, but did not differ from those measured on the 7(th) day of CT. There was no correlation between CD34+ cell counts and serum total cortisol (STC) levels on the 2(nd) and 7(th) days in the TBI or CT groups. CONCLUSION: An increase in CD34+ cell counts as observed on the 7(th) day in both TBI and CT groups suggested that CD34 changes were not specific to TBI. Moreover, this study showed for the first time that CD34 response was not affected by changes in cortisol levels induced by TBI and severity of TBI.

Measurement of hair iron concentration as a marker of body iron content.

The aim of the present study was to define the possible association between blood parameters and hair iron concentration in patient groups showing a difference in body iron content. The study population comprised subjects with iron deficiency anaemia and transfusion-related anaemia with different body iron contents and a healthy control group. All the cases included in the study were examined with respect to hair iron concentration, serum iron, total iron-binding capacity (TIBC), transferrin saturation and erythrocyte markers in the total blood count with ferritin values. Differences in hair iron concentration were evaluated between the groups. Correlation analysis was applied to define the association between the laboratory values used as markers of body iron content and hair iron concentration. A statistically significant difference was determined in hair iron 56Fe and 57Fe concentrations between the group with transfusion-related anaemia, the iron deficiency anaemia group and the healthy control group (P<0.001). In addition, a positive correlation was determined between hair iron 56Fe and 57Fe concentrations and serum iron, ferritin level, transferrin saturation, mean erythrocyte volume and mean erythrocyte haemoglobin values and a negative correlation with TIBC. In conclusion, the results of the present study showed a statistically significant difference in the hair iron concentrations of the patient groups with different body iron content and these values were correlated to the laboratory markers of body iron content.

Alveolar bone protective and hypoglycemic effects of systemic propolis treatment in experimental periodontitis and diabetes mellitus.

The aim of this study was to evaluate the efficacy of the anti-inflammatory effects of propolis on the systemic and local effects on experimental periodontitis and diabetes. Fifty-six Wistar rats were divided into seven groups: (1) negative-control (NC), (2) periodontitis (P), (3) diabetes (D), (4) diabetes+periodontitis (DP), (5) periodontitis+propolis (P-Pro), (6) diabetes+propolis (D-Pro), and (7) diabetes+periodontitis+propolis (DP-Pro). Periodontitis was induced by ligature placement and diabetes was induced by streptozotocin injection. Propolis (Pro) was administrated by oral gavage (100 mg/kg/day). On day 21, plasma was obtained for analysis and alveolar bone level was evaluated using histomorphometric analysis. Compared to NC the final blood glucose levels for D-Pro was not significantly different (P=.052), however, D, DP, and DP-Pro were significantly different. There were no statistically significant differences in blood glucose concentrations between P and P-Pro, between D and D-Pro, and between DP and DP-Pro. All groups showed significantly more alveolar bone loss compared with NC. A significant difference in bone loss was found between P and P-Pro, and DP and DP-Pro, however there was no difference between D and D-Pro. Plasma interleukin 1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-8 (MMP-8) levels were not significantly different among groups. In conclusion, propolis reduced fasting blood glucose levels in diabetes. In addition, propolis might be beneficial as an adjunct treatment of diabetes associated periodontitis and periodontitis without diabetes.

Investigation of trace elements in pterygium tissue.

PURPOSE: In this study, we compare the concentrations of the essential trace elements chromium (Cr), copper (Cu), selenium (Se), manganese (Mn), boron (B) and zinc (Zn) in both pterygium and normal conjunctiva and investigate the role they play in the development of pterygium. METHODS: Included in the study were 38 patients with pterygium and 38 control patients in matching age groups who had been operated on for strabismus or cataracts and in whom conjunctiva samples were collected from the nasal limbus area. All conjunctiva samples were kept at -80 °C until the performance of the biochemical investigations. The B, Cr, Mn, Cu, Zn and Se levels in the samples were then measured. The levels of all tissue trace elements were determined by using Agilent 7500a Inductively Coupled Plasma-Mass Spectrometer (Agilent Technologies, Santa Clara, CA). RESULTS: Cr, Mn, Zn and Se levels are significantly lower in the study group as compared to those of the control group (p < 0.001 for all four values). Regarding the level of B, there was no significant difference between the groups. The Cu levels of almost all subjects in the control group and all subjects in the pterygium group were under the detection limit. CONCLUSIONS: These findings indicate that remarkable differences in Mn, Zn, Se and Cr levels exist in pterygium tissues. Further investigation of electrolyte composition of the conjunctiva is needed to understand the genesis and developmental mechanism of pterygium.

Effect of serum selenium levels on radiotherapy-related toxicity in patients undergoing radiotherapy for head and neck cancer.

AIM: To investigate whether there is a difference in selenium levels before and after radiotherapy (RT) and to study the effects of serum selenium levels on RT-related toxicity in patients undergoing RT for head and neck cancer. PATIENTS AND METHODS: A population of 47 consecutive patients was enrolled in the study. RT was given by conventional fractionation. RT-related acute toxicity was evaluated once a week. Blood samples were obtained before and after RT to evaluate selenium levels. RESULTS: There was no significant difference between the levels of selenium before and after RT (58.09 ± 1.36 µg/l and 56.34 ± 1.11 µg/l, p-value=0.747, respectively). Grade III-IV mucositis, dysphagia, radiodermatitis, and nausea were seen in 6 (12.7%), 32 (68.2%), 24 (51.1%), and 3 (6.4%) patients, respectively. It was found that there was no statistically significant difference in the levels of selenium before and after RT, and no observed differences in regard to RT-related toxicities. CONCLUSION: The serum selenium levels do not affect RT-related toxicities.

Successful treatment of homozygous familial hypercholesterolemia using cascade filtration plasmapheresis.

OBJECTIVE: The aim of this study was to report the efficacy of low-density lipoprotein cholesterol (LDL-C) apheresisusing a cascade filtration system in pediatric patients with homozygous familial hypercholesterolemia (FH), and toclarify the associated adverse effects and difficulties. MATERIAL AND METHODS: LDL-C apheresis using a cascade filtration system was performed in 3 pediatric patientswith homozygous FH; in total, 120 apheresis sessions were performed. RESULTS: Cascade filtration therapy significantly reduced the mean LDL-C values from 418 ± 62 mg/dL to 145 ± 43 mg/dL (p= 0.011). We observed an acute mean reduction in the plasma level of total cholesterol (57.9%), LDL-C (70.8%),and high-density lipoprotein cholesterol (HDL-C) (40.7%). Treatments were well tolerated. The most frequent clinicaladverse effects were hypotension in 3 sessions (2.5%), chills (1.7%) in 2 sessions, and nausea/vomiting in 3 sessions(2.5%). CONCLUSION: Our experience using the cascade filtration system with 3 patients included good clinical outcomes andlaboratory findings, safe usage, and minor adverse effects and technical problems. CONFLICT OF INTEREST: None declared.

Efficacy of royal jelly on methotrexate-induced systemic oxidative stress and damage to small intestine in rats.

The aim of this present study is to investigate the mucositis caused by methotrexate (MTX), as well as whether the application of royal jelly (RJ) has a protective effect on oxidative stress. This present study included six groups each consisted of 12 Wistar rats. Distilled water (po: peroral) was given to the 1st group as placebo for 10 days and MTX (20 mg/kg, intraperitoneal: ip) on the 7th day. The 2nd group received RJ (50mg/kg, po) for 10 days and normal saline (NS) instead of MTX. RJ (50mg/kg) was given to the 3rd group for 10 days and MTX on the 7th day. The 4th group received RJ (100 mg/kg, po) for 10 days and NS was given intraperitoneally. RJ (100mg/kg) was given to the 5th group for 10 days and a single dose of MTX. Distilled water was given to the 6th (control) group for 10 days and intraperitoneal NS on the 7th day. Malondialdehyde (MDA), glutathione peroxidase and superoxide dismutase were analyzed in blood samples on the 11th day. Morphological and histopathological changes were examined in the intestinal tissue samples. Villus length and mucosal thickness, as well as the villus length/crypt ratio, were significantly decreased with MTX administration, and the semi-quantitative histological evaluation (SQHE) score was measured high (p<0.001). In addition, a decrease in the antioxidant parameters and an increase in the MDA levels were identified. The villus length and SQHE were significantly different in the groups receiving RJ (p<0.001) as compared to the MTX group. Although RJ addition had no effect on the decreased mucosal thickness and villus/crypt ratio in MTX groups, it caused an improvement in the antioxidant levels and a remarkable decrease in MDA levels. Adding RJ has a decreasing effect on the MTX-induced intestinal damage and it has a suppressive effect on MTX-induced oxidative stress by means of increasing antioxidant enzyme activity and decreasing lipid peroxidation.

The effects of long-term sleep deprivation on the long-term potentiation in the dentate gyrus and brain oxidation status in rats.

Some evidence suggests that sleep deprivation might impair synaptic plasticity and produce oxidative stress in the hippocampus. However it is not clear whether impairment of long-term potentiation depends on the oxidative stress evoked by sleep deprivation protocol. In this study we aimed to investigate the effects of a 21-day sleep deprivation period on long-term plasticity taking into account the stressful effect of sleep deprivation. Sleep deprivation was carried out using the multiple platforms method on adult male Wistar rats. Long-term potentiation was studied in the medial perforant pathway-dentate gyrus synapses. Elevated T test was applied, and blood corticosterone levels were measured. Lipid peroxidation products in whole brain and hippocampus were determined. No significant difference was found between the sleep deprived, pedestal and cage control groups at the end of the 21-day period when corticosterone levels were compared. The results of the elevated T test indicated that sleep deprivation did not change the anxiety-like behavior of the animals. When compared with cage or pedestal control groups, sleep deprived rats displayed elevated malondialdehyde levels, and decreased superoxide dismutase and glutathione peroxidase activities together with impaired long-term potentiation maintenance. It can be argued that 21-day SD may impair the maintenance of long-term potentiation evoked in the dentate gyrus, and the balance between oxidant and antioxidant defenses of the hippocampus.

The effect of grape seed extract on radiation-induced oxidative stress in the rat liver.

BACKGROUND/AIMS: The tolerance of the liver is considerably low when an effective radiation (RTx) dose needs to be delivered in patients in whom either their liver or whole body area has to be irradiated. The aim of this study was to evaluate the possible protective effect of grape seed extract on liver toxicity induced by RTx in the rat liver. METHODS: We used four groups, each consisting of 12 healthy male Wistar rats. RTx-grape seed extract group: rats were given grape seed extract (100 mg/kg) orally for seven days, following 8 Gy whole body irradiation, and grape seed extract was maintained for four days. RTx group: the same protocol was applied in this group; however, they received distilled water instead of grape seed extract. Grape seed extract group: only grape seed extract solution was administered for 11 consecutive days in the same fashion. CONTROL GROUP: only distilled water (orally) was administered in a similar manner. The level of malondialdehyde, an end product of lipid peroxidation, and the activities of superoxide dismutase and catalase, two important endogenous antioxidants, were evaluated in tissue homogenates. RESULTS: Grape seed extract was seen to protect the cellular membrane from oxidative damage and consequently from protein and lipid oxidation. In the RTx group, malondialdehyde levels were extremely higher than those of the grape seed extract-RTx group (p<0.001). Grape seed extract administration moderately reserved the malondialdehyde levels. RTx therapy decreased superoxide dismutase and catalase activities in the liver homogenates (p<0.001), and these alterations were significantly reversed by grape seed extract treatment (p<0.001). There were no differences between the grape seed extract- RTx, grape seed extract and control groups with regard to antioxidant activity (p>0.05). CONCLUSIONS: The levels of antioxidant parameters on RTx-induced liver toxicity were restored to control values with grape seed extract therapy. Grape seed extract may be promising as a therapeutic option in RTx-induced oxidative stress in the rat liver.

Role of grape seed extract on methotrexate induced oxidative stress in rat liver.

UNLABELLED: The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by its severe hepatotoxicity. Regarding the mechanisms of these adverse effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether grape seed extract (GSE), a new natural free radical scavenger, could ameliorate the MTX-induced oxidative injury in the rat liver. The animals were divided into 3 groups. Each group consisted of 12 animals. MTX-GSE group: rats were given GSE (100mg/kg body weight) orally for 15 days, and a single dose of MTX (20 mg/kg, intraperitoneally) was added on the 10th day. MTX group: these received placebo distilled water (orally) instead of GSE for 15 days and the same MTX protocol applied to this group on the 10th day. CONTROL GROUP: rats were given distilled water (orally) through 15 days and physiological saline (intraperitoneally) instead of MTX was administered on the 10th day in a similar manner. On the 16th day, liver tissue samples were obtained under deep anaesthesia. The level of malondialdehyde (MDA), an end product of lipid peroxidation, and the activities of süperoxide dismutase (SOD) and catalase (CAT), two important endogenous antioxidants, were evaluated in the tissue homogenates. MTX administration increased the MDA level and decreased the SOD and CAT activities in the liver homogenates (p < 0.001), while these alterations were significantly reversed by GSE treatment (p < 0.001). MTX led to significantly reduced whole blood count parameters (p < 0.05). When GSE was supplemented, no significant changes in blood count parameters were noted. It appears that GSE protects the rat liver and inhibits methotrexate-induced oxidative stress. These data indicate that GSE may be of therapeutic benefit when used with MTX.

Disturbance of pro-oxidative/antioxidative balance in allogeneic peripheral blood stem cell transplantation.

High dose chemotherapy causes increased free radical formation and depletion of tissue antioxidants. Whether allogeneic hematopoietic stem cell transplantation (HSCT) has an effect on oxidative stress is uncertain. The aims of the study were to determine the effect of allogeneic HSCT on plasma concentrations of antioxidants and oxidative stress biomarkers, and to investigate their relationships with graft-versus-host disease (GVHD), conditioning regimens, and transplant-related mortality (TRM) in patients with hematological malignancies. Patients (n=25) undergoing allogeneic HSCT from HLA-matched sibling donors were enrolled in the study. Plasma oxidant and antioxidant status were measured at day -1 before transplantation and 30 days after HSCT. In both myeloablative (n=14) and non-myeloablative (n=11) transplant groups, the mean levels of plasma malondialdehyde (MDA) and nitric oxide (NO) increased after allogeneic HSCT (p <0.01), whereas superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities decreased compared with baseline values (p <0.01). No significant relationships were found between either the pretransplant or post-transplant mean levels of the oxidative stress parameters and the existence of graft-versus-host disease (GVHD), the type of conditioning regimen, or transplant related mortality (TRM). This study documents a significant disturbance of pro-oxidative/antioxidative balance in the plasma of patients undergoing allogeneic HSCT regardless of the intensity of the conditioning regimen.