Native Thiol Research Articles

Research of Importance of Thiol, CRP and Lactate in Diagnosing Mesenteric Ischemia At An Early Stage: Animal Model.

Acute mesenteric ischemia is especially seen in the elderly population. It has an increasing incidence in today's world where the average life expectancy is increasing. Early diagnosis is the most important factor reducing morbidity and mortality, and there is still no marker with high sensitivity and specificity for early diagnosis.In this study, we aimed to find a more sensitive and specific serum marker in the early diagnosis of mesenteric ischemia by comparing thiol with the currently used markers C-reactive protein and lactate. In our study, 32 Wistar Albino male rats, 10-12 weeks old, weighing 250-300 g, were used. 32 rats were divided into 4 groups, one of which was the control group. The superior mesenteric artery of the other 3 groups was ligated. Blood samples were taken after 2 hours from the first group, 4 hours from the second group, and 6 hours from the third group. Then the rats were sacrificed. Mesenteric ischemia and its level were observed in sacrificed subjects. The samples were separated under appropriate conditions and analyzed biochemically. As the ischemia time increased, CRP increased and this increase was found to be statistically insignificant (p>0.05). The changes in lactate were found to be statistically significant (p<0.05). The difference between the changes of total and native thiol values was found to be statistically significant (p<0.05). Although CRP is a non-specific parameter in the early diagnosis of acute mesenteric ischemia, lactate maintains its importance as seen in our study. Differences in total thiol and native thiol changes were statistically significant. The fact that this significant difference is observed at the 4th hour values, reveals the importance of these parameters in early diagnosis. Thanks to the economic and fast results of thiol parameters, it is thought that new studies to be added to the literature can lead to the diagnosis of mesenteric ischemia.

The Evaluation of Dynamic Thiol/Disulfide Homeostasis in Papillary Thyroid Carcinoma

Objectives: Aim of this study is to analyze the correlation between thiol/disulfide homeostasis (TDH) and papillary thyroid carcinoma (PTCA) and to reveal the possible impact of TDH on the development of PTCA. Material and Methods: Preoperative venous blood sampling was obtained from the patients having applied to our hospital due to euthyroid nodular goiter and detected with suspected malignancy or malignant cytology in FNAB, according to the BETHESDA system. Those whose postoperative histopathological results proved the presence of PTCA were involved in this study. Healthy volunteers who were without any thyroid nodules and thyroid dysfunction. Results: The number of participants in the patient and control groups was 34 and 101, respectively. Compared to the control group, native thiol (μmol/L), total thiol (μmol/L), and native thiol/total thiol × 100 values were ascertained to be lower in the patient group with PTCA; however, these values were not statistically significant. Disulfide, disulfide/native thiol × 100, and disulfide/total thiol × 100 values were detected to be lower in the patient group with PTCA, but not statistically significant. When the patients with PTCA were assessed within themselves, TDH parameters were not associated with the PTCA subtype, the number of foci, the presence of lymphovascular invasion, and the presence of metastatic lap. Conclusion: Considering the parameters of PTCA and TDH, the results were not statistically significant. And besides postoperative histopathological findings such as the PTCA subtype, the number of foci, the presence of lymphovascular invasion, and presence of metastatic lap were not correlated with THD parameters.

MiR-21, miR-221, and miR-222 upregulation in lung cancer promotes metastasis by reducing oxidative stress and apoptosis.

The purpose of our research was to observe the effects of miR-21, miR-221, and miR-222, as well as their target genes on oxidative stress, lung cancer formation, and metastasis. Positron emission tomography/computed tomography, fiberoptic bronchoscopy, and/or endobronchial ultrasonography were performed on a total of 69 lung cancer patients to detect the presence or absence of metastasis, and the patients were classified based on the types of cancer. Total RNA and miRNA were isolated from the obtained biopsy samples. The quantitative analysis of hsa-miR-21-5p, hsa-miR-222-3p, and hsa-miR-221-3p and their target genes was performed by the RT-qPCR method. In determining oxidative stress, total antioxidant status and total oxidant status in tissue and total thiol and native thiol in blood were determined spectrophotometrically. OSI and disulfide were calculated. We discovered that the metastasis group had higher levels of hsa-miR-21-5p, hsa-miR-221-3p, and hsa-miR-222-3p (p<0.05). While TIMP3, PTEN, and apoptotic genes decreased in metastasis, anti-apoptotic genes increased (p<0.05). In addition, while oxidative stress decreased in the metastasis group, no change was found in the serum (p>0.05). Our findings show that upregulation of hsa-miR-21-5p, hsa-miR-221-3p, and hsa-miR-222-3p effectively contributes to both proliferation and invasion by influencing oxidative stress and mitochondrial apoptosis.

Investigation of the clinical efficacy of thiol-disulfide homeostasis, delta neutrophil index, and ischemia-modified albumin in cases of incarcerated and strangulated hernia.

The treatment of patients presenting with the diagnosis of incarcerated and/or strangulated inguinal hernia is mostly surgery. If strangulation and necrosis are present, the need for laparotomy arises, which may increase the risk of morbidity. Currently, it is not possible to clearly determine whether there is bowel ischemia and necrosis before surgery. In this study, we aimed to investigate the clinical efficacy of the thiol-disulfide homeostasis, delta neutrophil index (DNI), and ischemia-modified albumin (IMA) parameters in incarcerated and strangulated hernia cases. Patients that presented to the general surgery outpatient clinic due to inguinal hernia or to the emergency department of the hospital with a preliminary diagnosis of incarcerated and/or strangulated hernia in April 2021-November 2021 were included in the study. The patients were divided into the following four groups: patients that underwent elective repair for inguinal hernia (Group 1), those who were followed up without surgery due to incarcerated hernia (Group 2), those who underwent hernia repair without bowel resection due to incarceration (Group 3), and those who underwent bowel resection due to strangulation (Group 4). Group 1 was defined as the control group, while Groups 2, 3, and Group 4 were evaluated as the incarcerated/strangulated hernia group. The demographic data of the patients, length of hospital stay, body mass index, comorbidities, medical history and physical examina-tion findings, radiological examinations, treatments applied, white blood cell (WBC) count, lactate, and DNI, thiol-disulfide and IMA parameters were evaluated. The WBC count, disulfide/native thiol, disulfide/total thiol, and IMA values were significantly higher in the incarcerated/strangulated hernia group than in the control group, while the native thiol and total thiol values were higher in the latter than in the former (P<0.05). There was no statistically significant difference between the groups in terms of lactate (P>0.05), but the mean WBC count was higher in Group 4 compared to Group 1, and the mean DNI was significantly higher among the patients who underwent bowel resection and anastomosis than in those that were followed up and discharged (P<0.05). We consider that the preoperative evaluation of the thiol-disulfide homeostasis, IMA, and DNI parameters in incarcerated/strangulated hernia cases can be an effective and easily applicable method in predicting difficulties that may be encountered intraoperatively and the surgical procedure to be applied to the patient.

Evaluation of adult immunoglobulin A vasculitis with oxidative stress and inflammation biomarkers

IgA vasculitis (IgAV) is a leukocytoclastic vasculitis affecting small vessels and is more common in children than in adults. In this study, we aimed to investigate the effects of oxidative stress in adult IgAV patients by Dynamic Thiol Disulfide Homeostasis (DTDH) and Ischemia Modified Albumin (IMA) levels. We also aimed to correlate the presence of inflammation detected by C-Reactive Protein (CRP) and Highly Sensitive C-Reactive Protein (hsCRP) with these oxidative stress parameters. Forty-one IgAV patients and forty-five controls were included in the study. Patients were classified as "active" or "in remission" according to the British Vasculitis Activity Score (BVAS). Measured parameters were compared between the groups. DTDH, IMA, CRP and hsCRP parameters were analyzed in both patient and control groups. According to our results, disulfide (p=0.047), index 1 (p&lt;0.001), index 2 (p&lt;0.001), IMA (p&lt;0.001), CRP (p=0.005) and hsCRP (p=0.004) levels were significantly increased while native thiol (p&lt;0.001), total thiol (p&lt;0.001) and index 3 (p&lt;0.001) levels were significantly decreased in IgAV patients. The results of this study show that oxidative stress is associated with IgAV disease and also with disease severity. The oxidative stress parameters evaluated were also correlated with markers of inflammation.

Comparison of 'primary repair' and 'placing a drain without repair' methods in duodenum perforations.

Duodenal ulcer perforation is a serious condition. A number of methods have been defined and used in surgical treatment. In this study, it was aimed to compare the effectiveness of 'primary repair' and 'drain placement without repair' methods in duodenal perforations using an animal model. Three equivalent groups of ten rats each were formed. Perforation was created in the duodenum in the first (primary repair/sutured group) and the second group (drain placement without repair/sutureless drainage group). In the first group, the per-foration was repaired with sutures. In the second group, only a drain was placed in the abdomen without sutures. In the third group (control group), only laparotomy was performed. Neutrophil count, sedimentation, serum C-reactive protein (CRP), serum total an-tioxidant capacity (TAC), serum total thiol, serum native thiol, and serum myeloperoxidase (MPO) analyses were performed on animal subjects in the pre-operative period and on the post-operative 1st and 7th days. Histological and immunohistochemical (transforming growth factor-beta 1 [TGF-β1]) analyzes were performed. Blood analysis, histological, and immunohistochemical findings obtained from the groups were compared statistically. There was no significant difference between the first and second groups, except for the TAC on the post-operative 7th day and MPO values on the post-operative 1st day (P>0.05). Although tissue healing was more pronounced in the second group than in the first group, there was no significant difference between the groups (P>0.05). TGF-β1 immunoreactivity observed in the second group was found to be significantly higher than in the first group (P<0.05). We think that the sutureless drainage method is as effective as the primary repair method in the treatment of duo-denal ulcer perforation and can be safely applied as an alternative to the primary repair method. However, further studies are needed to fully determine the efficacy of the sutureless drainage method.

Effects of NO, H2S and CO on Thiol/Disulfide Balance and Advanced Oxidation Protein Products in Hippocampus and Serum

Introduction: Nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO) are known as gaseous autocoids. It is not clear how the application of exogenous NO, H2S and CO alters the thiol/disulfide balance and advanced oxidation protein products (AOPPs) in the hippocampus and serum. Materials and Methods: In the study, rats were exogenously injected with L-arginine (100 mg/kg) as a NO donor, NaHS (10 mg/ kg) as a H2S donor, and CORM-2 (10 mg/kg) as a CO donor (II) (a tricarbonyldichlororuthenium dimer). Thiol/disulfide balance and advanced protein oxidation products were analyzed in hippocampus and serum samples. Results: The native thiol level in the hippocampus of the L-arginine group was statistically decreased compared to the native thiol level of the control group (p≤0.0001). The disulfide level in the hippocampus of the L-arginine group was statistically increased compared to the control group (p=0.009). Hippocampal total thiol level of NaHS group and CORM-2 group increased statistically (p=0.008,p=0.0157, respectively), while serum disulfide level of CORM-2 group decreased (p=0.0005). Serum and hippocampus AOPPs levels of the NaHS group were statistically increased compared to the control group (***p=0.0006, **p=0.0047, respectively). Similarly, the hippocampal AOPP level in the CORM-2 group was found to be statistically increased compared to the AOPP level in the control group (p=0.0437). Conclusion: As NaHS can improve thiol/disulfide balance, new studies are needed for CORM-2 and L-Arginine. This study is the first to report the effects of NO, H2S and CO on thiol/disulfide balance and AOPPs in the hippocampus and serum. Keywords: NO, H2S, CO, AOPPs, Thiol/disulfide

Effects of amifostine against blunt chest trauma-induced cardiac injury in rats.

This study aimed to examine whether two different doses of dexamethasone (DXM), which is a corticosteroid, and amifostine (AMI), which reduces cumulative tissue toxicity induced by cisplatin in advanced-stage cancer patients, have ameliorative effects on pathologic changes associated with cardiac contusion (CC) induced in rats. Forty-two Wistar albino rats were equally divided into six groups (n=7): C, CC, CC+AMI 400, CC+AMI 200, CC+AMI+DXM, and CC+DXM. Tomography images and electrocardiographic analyzes were performed, mean arterial pressure was measured from the carotid artery, and blood and tissue samples were obtained for histopathological and biochemical analyses after trauma-induced CC. While the total oxidant status and disulfide parameters in the cardiac tissue and serum were significantly higher (p<0.05), the total antioxidant status, total thiol, and native thiol parameters were significantly lower (p<0.01) in rats with trauma-induced CC. The most frequently observed finding in the electrocardiography analyze was ST elevation. According to evaluation based on histological, biochemical, and electrocardiographic examinations, we believe that only 400 mg/kg dose of AMI or DXM can be effective in the treatment of myocardial contusion in rats. Evaluation based on histological findings.

Dynamic thiol-disulphide homeostasis and ischemia modified albumin levels in neonatal calf diarrhea

The aim of this study was to determine dynamic thiol-disulphide homeostasis (TDH) parameters and ischemia modified albumin (IMA) levels in calves with neonatal diarrhea and compare with healthy controls. A total of 50 calves were included in the study. There were 25 calves in both diarrhea and healthy groups. Serum native thiol, total thiol, disulfide and IMA levels were measured using new methods. Native thiol (P=0.025) and total thiol (P=0.041) values decreased significantly in calves with neonatal diarrhea compared to the healthy control group. Disulphide (P= 0.133), disulphide/native thiol ratio (P=0.001) and IMA (P=0.0018) parameters were lower in healthy group, and the difference between the two groups was significant for the parameters other than disulphide. This study shows that TDH is impaired in neonatal calf diarrhea and IMA levels are increased due to oxidative stress.

Evaluation of Thiol/Disulfide Homeostasis and Neurogenin 3 Levels as a Marker of Oxidative Stress in Children and Adolescents Newly Diagnosed with Type 1 Diabetes

The objective of the study was to determine the relationship between autoimmunity and dynamic thiol/disulfide, neurogenin 3 (ngn 3) status in the newly diagnosed with type 1 diabetes mellitus (T1DM), the level of treatment, and thiol/disulfide homeostasis and neurogenin 3, and to found the changes in neurogenin 3 level due to beta cell damage in children newly diagnosed with T1DM. Totally 60 children aged 1-18 years old, 30 of them newly diagnosed with type 1 diabetes (patients), and 30 of them healthy children in the same age group (control) were included in the study. Insulin and C-peptide levels of newly diagnosed T1DM patients were lower than the control group, however, HbA1c, glucose, creatinine, cholesterol, triglyceride, and LDL levels were found higher in patients. Total thiol level and Gad antibody positive rate were found higher in children newly diagnosed with T1DM. In addition, it was observed that the rate of anti-insulin antibody positivity increased in the 6th-month control of patients. However, HbA1c and glucose levels at diagnosis were higher in patients compared to the control group at the sixth month. Insulin and C-peptide levels were determined lower in patients admitted with diabetic ketoacidosis. A negative correlation was observed between native thiol and anti-insulin antibody parameters and a positive correlation between ngn 3 and total cholesterol and LDL. In conclusion, thiol/disulfide homeostasis and ngn 3 parameters can be used as oxidative stress markers in children and adolescents newly diagnosed with T1DM.

Evaluation of the effects of empagliflozin on acute lung injury in rat intestinal ischemia-reperfusion model.

Empagliflozin is a selective sodium-glucose co-transporter (SGLT2) inhibitor that is approved for the treatment of type 2 diabetes. The beneficial effects of empagliflozin on other organ systems including the heart and kidneys have been proven. The aim of this study is to evaluate the role of empagliflozin on acute lung injury induced by intestinal ischemia-reperfusion (I/R). A total of 27 male Wistar albino rats were divided into three groups: sham, I/R, and I/R + empagliflozin; each group containing nine animals. Sham group rats underwent laparotomy without I/R injury. Rats in the I/R group underwent laparotomy, 1h of after ischemia-reperfusion injury (superior mesenteric artery ligation was followed by 2h of reperfusion). Rats in I/R were given empagliflozin (30mg/kg) by gastric gavage for 7days before the ischemia-reperfusion injury. All animals were killed at the end of reperfusion and lung tissue samples were obtained for immunohistochemical staining and histopathological investigation in all groups. Serum glucose, AST, ALT, creatinine, native thiol, total thiol, and disulfide levels and disulfide-native thiol, disulfide-total thiol, and native thiol-total thiol ratios as well as the IMA levels were analyzed and compared among the groups. While intestinal I/R significantly increases serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine levels; did not cause any change in homeostasis parameters and IMA level. Empagliflozin treatment had no significant effect on biochemical parameters. Empagliflozin treatment induced a significant decrease in positive immunostaining for IL-1, IL-6, TNF-alpha, caspase 3, caspase 8, and caspase 9 compared to the I/R group in lung tissue samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall, and infiltration of inflammatory cells into alveolar spaces. Empagliflozin treatment significantly attenuated the severity of intestinal I/R injury. It was concluded that empagliflozin treatment may have beneficial effects in acute lung injury, and, therefore, has the potential for clinical use.

Direct-acting antiviral therapy may help restore HCV-induced impaired redox balance and liver fibrosis process

Abstract Objectives The aim of this study was to investigate the changes in thiol/disulfide balance, pro-fibrotic mediators (transforming growth factor-beta [TGF-β] and periostin) and a potential biomarker for the prediction of HCV-induced HCC (3β-hydroxysterol Δ24-reductase [DHCR24]) during direct-acting antiviral (DAA) therapy in chronic hepatitis C (CHC) patients. Methods This prospective cohort study included 56 non-cirrhotic, treatment-naive CHC patients who were treated with DAAs between January and June 2020. Laboratory tests, including serum total/native thiol, TGF-β , $\text{,}$ periostin, DHCR24, total bilirubin and albumin levels were measured and disulfide levels were calculated at baseline, then at 1 month and at the end of therapy (EOT). Results Of the 56 patients, all achieved a sustained virological response after DAA therapy. There was a significant decrease in serum levels of disulfide and TGF-β, (p=0.020 and p&lt;0.001, respectively) and a significant increase in serum levels of native thiol compared with baseline levels (p=0.010). There was no significant change in levels of total thiol, DHCR24 and periostin levels. Serum TGF-β levels were found to be positively correlated with total bilirubin levels (rs=0.470, p=0.001) and negatively with albumin levels (rs=−0.483, p&lt;0.001). A significant moderate positive correlation was determined between baseline serum DHRC24 and disulfide levels (rs=0.356, p=0.007). Conclusions The study results suggest that the DAA therapy may help to restore the impaired thiol/disulfide balance and reduce the pro-fibrotic process in CHC patients by markedly decreasing serum levels of TGF-β, a key player in HCV-induced liver fibrosis.

Evaluation of thiol/disulfide homeostasis in rheumatoid arthritis and disease activity

BackgroundIt has been suggested that the deterioration in the antioxidant defense system due to thiols may cause the pro-oxidant/antioxidant imbalance seen in rheumatoid arthritis (RA). This study was conducted to evaluate thiol/disulfide (−SH/−SS) homeostasis in patients with RA compared to healthy controls, and to validate the limited number of studies examining the relationship between Disease Activity Score-28 (DAS28) and thiol parameters. MethodA total of 100 individuals (mean age: 46.3 ± 12.03) consisting of 86 females and 14 males were included in the RA group, and a total of 100 individuals (mean age: 43.3 ± 10.96 years) consisting of 78 females and 22 males were included in the control group. DAS28 was used to assess RA disease activity. −SH/−SS homeostasis parameters were measured using the automated spectrophotometric method described by Erel and Neselioğlu. ResultsWhile native thiol (−SH) (p:0.001), total thiol (−SH + −SS) (p < 0.0001) levels and −SH\\(−SS + −SH) ratio (p: 0.018) were lower in the RA group compared to the healthy controls, disulfide (−SS) level (p: 0.005)), −SS\\−SH (p: 0.001) and −SS\\(−SS + -SH) (p: 0.002) ratios were found to be higher. In the control group and the group in remission (defined by DAS28 < 2.6), the median values of –SH (p:0.002) and −SS + −SH (p:0.0008) were found to be significantly higher, and the median value of –SS (p: 0.001) was found to be lower compared to the other DAS28 groups. While a negative correlation was found between DAS28 and –SH (r: −0.243, p: 0.007), a positive correlation was found between DAS28 and −SS (r: 0.316, p: 0.0003), −SS\\−SH (r:0.229, p: 0.002) and −SS\\(−SS + −SH) (r: 0.285, p: 0.0009). ConclusionsThe plasma thiol antioxidant pool was decreased in RA compared to healthy controls and those with active disease compared to those in remission.

Thiol-disulphide Homeostasıs and Ischemia-modified Albumın Level and its Relatıonshıp with Clınicopathological Features of Breast Cancer.

To investigate the status of thiol-disulphide homeostasis and ischemic-modified albumin and their association with clinicopathological parameters in breast cancer. A cross-sectional descriptive study. Department of Internal Medicine and Department of Medical Oncology, Dicle University, Turkey, from April to September 2021. Forty treatment-naive female patients diagnosed with breast cancer who presented to the Oncology Clinic of the hospital and 33 healthy women with no comorbidities were included. Serum levels of native thiol (NT), disulphide (Ds), total thiol (TT), IMA (ischemic modified albumin) at diagnosis and disulphide/native thiol (Ds/NT), disulphide/total thiol (Ds/TT), and the ratios of native thiol/total thiol (NT/TT) were analysed by the colorimetric method. Median age at diagnosis was 44 (29-70) years. The majority of patients had stage II-III disease (77.5%). Mean serum levels of TT were significantly lower in breast cancer patients (462.45 ± 100.2 μmol/L) compared to healthy controls (507.28 ± 75.72 μmol/L) (p=0.038). Mean serum levels of Ds were significantly lower in breast cancer patients (20.25 ± 5.94 μmol/L) compared to healthy controls (22.99 ± 3.56 μmol/L) (p=0.018). Meanwhile, mean IMA levels were significantly higher in breast cancer patients (0.81 ± 0.05 μmol/L) compared to healthy controls (0.73 ± 0.19 μmol/L) (p=0.016). NT and TT levels showed a moderate correlation with the percentage of fat mass and body mass index (BMI), and a weak correlation with age (p<0.05). Univariate and multivariate analyses examining the association between thiol-disulphide levels and patient clinical characteristics demonstrated that NT and TT levels had a statistically significant relationship with body mass index and menopausal status (p<0.05), with lower levels of NT and TT in postmenopausal patients and patients with high BMI. Decreased TT and Ds levels and increased IMA levels were determined in patients diagnosed with breast cancer compared to the healthy control group. Thiol-disulphide levels were observed to be associated with clinical characteristics such as menopausal status and BMI. Breast cancer, Thiol, Ischemic modified albumin.

Thiol-disulfide balance and trace element levels in patients with seasonal allergic rhinitis.

The prevalence of allergic diseases is gradually increasing worldwide. The most common such allergic disease is allergic rhinitis (AR). The present study investigated the possible relationship between seasonal AR and the thiol-disulfide balance and zinc and copper levels in adult individuals. 130 male and female adults were included in the study. The participants' serum thiol-disulfide balance and zinc and copper levels were measured spectrophotometrically using commercial kits. Statistical significance was accepted as p < 0.05 between the groups. The serum copper (p = 0.001), native thiol (p = 0.006), reduced thiol (p < 0.001), and thiol oxidation reduction ratio (p < 0.001) levels were significantly lower in the seasonal AR group than in the control group. In AR patients, the low level of copper, which is an important trace element, the deterioration of the thiol-disulfide balance, which represents a unique indicator of the oxidant-antioxidant balance, the increased disulfide level caused by oxidative stress, and the decreased native thiol level can all serve as important biochemical markers.

Oxidative stress indicators during the course of acute graft versus host disease

Aim: This prospective study aimed to observe the changes in oxidative stress indicators, including total anti-oxidant status (TAS), total oxidant status (TOS), paraoxanase-1 (PON1), total thiol (TT), native thiol (NT), disulphide (DS) and nitric oxide (NO) levels from sequential blood samples obtained during a de-novo episode of acute graft versus host disease (aGvHD) and evaluate their association with disease severity and the risk of steroid resistant disease.&#x0D; Material and Method: Sequential patients who underwent an allogeneic stem cell transplantation (ASCT) in our unit and subsequently developed a de-novo episode of aGvHD between January 2022 and May 2022 were included in case they gave informed consent. All patients were started high dose (2 mg/kg/day) methylprednisolone as institutional standard first-line treatment of aGvHD as soon as the clinical diagnosis is evident. All episodes were confirmed simultaneously with gastrointestinal (GI) endoscopy and/or skin biopsies. TAS, TOS, PON1, TT, NT, DS and NO were studied from blood samples collected on days 0, +3 and +7 of steroid treatment. Demographic characteristics, diagnoses, donor type, GvHD prophylaxis, stage and grade of aGvHD, performance status (PS), the presence of cytomegalovirus (CMV) reactivation and response to steroid therapy were also noted.&#x0D; Results: A total of 15 cases was included. The median age was 49 (23-77). Males constituted 60.0% (n=9). The most frequent diagnosis and donor type were acute leukemia (53.3%, n=8) and matched related donor (46.7%, n=7), respectively. High grade aGvHD with Glucksberg grading and International Bone Marrow Transplant Registry severity index (IBMTR-SI) included 53,3% (n=8) and 86.7% (n=10) of cases, respectively. Non-responders (20.0%, n=3) significantly had advanced stage GI involvement, higher grade of aGvHD with Glucksberg grading and IBMTR-SI, and lower PS (p=0.005, p=0.04, p=0.006, and p=0.02, respectively). The changes in TAS, TOS, PON1, TT, NT, DS and NO levels on days 0, +3 and +7 of steroid treatment were not significant. Median PON1 levels on days 0, +3 and +7 of steroid treatment were significantly lower among non-responders (p

Silibinin Effect on Methotrexate-Induced Hepatotoxicity in Rats.

Hepatotoxicity is one of the major side effects of methotrexate and limits its use. In this study, we investigated the hepatoprotective effect of silibinin and the role of oxidative stress markers and cytokines on high-dose methotrexate-induced hepatotoxicity in rats. In this study, rats were randomly divided into 5 groups (n=7). Methotrexate (20 mg/kg, intraperitoneally) was administered on the first day in all groups except control. Silibinin was injected for 5 days to methotrexate-silibinin25, methotrexate-silibinin50, and methotrexate-silibinin100 groups at a dose of 25, 50, and 100 mg/kg/day, respectively. On the sixth day, blood and liver samples were obtained and rats were sacrificed. Serum total antioxidant capacity, total oxidant status, total thiol, native thiol, alanine aminotransferase, aspartate transaminase, bilirubin, albumin, tumor necrosis factor-alpha, and interleukin-10 levels were measured. In addition, a histopathological evaluation of liver tissues was performed. Methotrexate reduced total antioxidant capacity and increased disulfide/total thiol ratio. Histopathologic examination revealed that methotrexate increased hepatic damage and 50 mg/kg/dose of silibinin prevented inflammatory cell infiltration in particular. Our results suggest that silibinin (50 mg/kg/day) may reduce the hepatic damage in methotrexate-induced hepatotoxicity in rats by increasing antioxidant capacity.

Examination of antimicrobial effect of fluoxetine in experimental sepsis model: An in vivostudy.

Since most infectious diseases can develop into sepsis, it is still a major medical problem. Some in-vivo studies showed promising properties of fluoxetine in the treatment of infections. This study aims the antimicrobial effect of fluoxetine on the inflammatory process used in the treatment of sepsis-modeled rats. Besides, to investigate the efficacy of fluoxetine on modifying the antibiotic effect of imipenem in the inflammatory response.An experimental sepsis model was divided intonegative control, positive control, fluoxetine 5 mg/kg, imipenem 60 mg/kg, and combined (fluoxetine; imipenem). Procalcitonin (PCT),high-sensitivity C-reactive protein (hs-CRP), lactate, myeloperoxidase activity (MPO), the inflammation markers interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels were measured by enzyme-linked immunosorbent assay method. Oxidative stress markers, total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), and native thiol (NT) were measured using photometric methods. Oxidative stress index (OSI) was calculated according to TAS and TOS levels. The statistical analysis was performed by Statistical Package for Social Sciences version 22.0.After treatment with fluoxetine, imipenem, and combined groups, IL-1β, IL-6, TNF-α, MPO activity, MCP-1, hs-CRP, PCT, lactate, and the oxidative stress markers OSI, and disulfide levels were decreased (p < 0.05). The TT, NT, and TAS levels significantly statistically increased (p < 0.05).This research demonstrates that fluoxetine has effects as anti-inflammatory and antioxidant, and the combined treatment with antibioticum imipenem indicates positive synergistic effects in the experimental sepsis model.

Beneficial effects of vitamin B12 treatment in pediatric patients diagnosed with vitamin B12 deficiency regarding total-native thiol, oxidative stress, and mononuclear leukocyte DNA damage

Vitamin B12 is involved in biochemical metabolic pathways. B12 deficiency is common in childhood when the need for the vitamin increases and growth and development occur. Various hematological, neurological, psychiatric, and gastrointestinal disorders are observed in its deficiency. In addition, B12 deficiency is associated with oxidative stress and DNA damage. Therefore, the aim of our study is to evaluate oxidative stress, thiol/disulfide homeostasis, and DNA damage pre and post-treatment in children diagnosed with B12 deficiency. A total of 40 children with B12 deficiency were included in the study after the consent form was approved. Blood was drawn from children pre and posttreatment. Hemoglobin (HGB), hematocrit (HCT), and red blood cells (RBC) were measured by autoanalyzer; total antioxidant status (TAS), total oxidant status (TOS), total thiol (TT), and native thiol (NT) were measured by the photometric method, and DNA damage was analyzed by the comet assay method. Oxidative stress index (OSI) and disulfide (DIS) values were calculated. As a result of the experiments, HGB, HCT, and RBC increased with treatment. While TAS, TT, and NT as antioxidant parameters increased; TOS, OSI, and DIS decreased with treatment compared to pretreatment. DNA damage was also found to decrease with treatment. Additionally, these data were statistically significant (p < 0.001). It was found that oxidative stress and DNA damage decreased with oral B12 treatment in children with B12 deficiency, and clinical parameters were also improved.

Evaluation of Oxidative Stress by Dynamic Thiol/Disulfide Homeostasis and Ischemia-Modified Albumin Levels in Children with β-Thalassemia Major.

β-thalassemia major (β-TM) is a hemoglobinopathy characterized by reduced or absent β-globin production. A balance remains between the production of free radicals and suppression of increased levels of reactive oxygen species by the antioxidant system. This study aimed to examine thiol/disulfide homeostasis (TDH) and serum ischemia-modified albumin (IMA) levels to evaluate the oxidant/antioxidant balance in healthy children and persons with β-TM receiving and not receiving chelation therapy. This prospective study was carried out from January to June 2021 among 46 individuals with β-TM and 35 healthy controls. A spectrophotometric method was used to analyze TDH and IMA concentrations. We found that, compared to controls, native thiol (NT) (P = .048) and total thiol (TT) (P = .027) values were lower in the patient group, whereas disulfide (P < .001), disulfide/native thiol (D/NT) (P = .004), disulfide/total thiol (D/TT) (P = .005), native thiol/total thiol (NT/TT) (P = .004) and IMA (P = .045) values were higher. NT and TT levels were significantly lower in the chelation- group compared to the chelation+ and control groups (P = .002, P = .001). D/NT, D/TT, and NT/TT levels were higher in the chelation+ group than the control group (P = .007), and IMA levels were significantly higher in the chelation+ and chelation- groups compared to the control group (P = .002). The receiver operating characteristic analysis demonstrated that IMA levels were significantly higher in the children with β-TM not taking regular chelation therapy. Thiol/disulfide homeostasis was observed to be weakened in children with β-TM in our study. Our findings show that when children with β-TM do not receive regular chelation therapy, their oxidant imbalance worsens.