Total Antioxidant Status Levels Research Articles

Selenium exerts protective effects on inflammatory cardiovascular damage: molecular aspects via SIRT1/p53 and Cyt-c/Cas-3 pathways

Systemic inflammatory response could affect many systems. Cardiac dysfunction develops due to cardiovascular system damage and could be mortal. Selenium is a trace element that can be used as a dietary supplement and has antioxidant, anti-inflammatory, and anti-apoptotic properties. This study aims to evaluate the protective effects of selenium on cardiovascular damage via silenced information regulator 1 (SIRT1)/p53 and cytochrome C (Cyt-c)/ caspase-3 (Cas-3) pathways. Thirty-two rats were randomly divided into 4 groups as control, LPS (0.1mg/kg, intraperitoneally(i.p.), 2-7 days) and LPS + Selenium (LPS-0.1mg/kg, i.p., 2-7 days, selenium - 100µg/kg, i.p., 1-7 days) and selenium (100µg/kg, i.p., 1-7 days) group. On the 8th day of the experiment, rats were sacrificed. Blood samples and half of the left ventricles were collected for biochemical and genetic analysis. The remaining left ventricles and aorta were taken for histological and immunohistochemical analysis. In the LPS group myocardial hemorrhages, hyperemia, and endothelial cell loss were observed. Also, Cas-3 and vascular endothelial growth factor (VEGF) expressions; creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), ischemia modified albumin (IMA), total oxidant status (TOS), oxidative stress index (OSI) levels; p53, Cyt-c, Cas-3 mRNA expressions increased while total antioxidant status (TAS) levels, glutathione peroxidase (GPx) activity, SIRT1 mRNA expression decreased. Selenium treatment reversed all these changes. Selenium showed protective effects on cardiovascular injury via regulating SIRT1/p53 and Cyt-c/Cas-3 pathways. This study enlightened the possible usage of selenium on cardiotoxicity.

Evaluation of erythrocyte arginase activity, plasma nitric oxide concentration and oxidative stress status in cattle with anaplasmosis

Bovine anaplasmosis is an arthropod-borne disease characterized by high fever, anaemia and sometimes jaundice. The role of oxidative stress in anaplasmosis has been investigated, but erythrocyte arginase (ARG) activity has not been studied. In this study, we aimed to investigate the changes in haematological parameters, erythrocyte ARG activity, plasma nitric oxide (NO) levels and oxidative stress parameters and explain the relationship between each other in cattle with anaplasmosis. The material of this study consisted of 14 cattle, aged 10–12 months with anaplasmosis (infected group) and 14 healthy cattle aged 10–12 months (control group). Our data revealed that leukocyte parameters and plasma NO levels and serum malondialdehyde (MDA), total oxidant status (TOS) and oxidative stress index (OSI) levels were higher while erythrocyte parameters, erythrocyte ARG activity and serum total antioxidant status (TAS) and glutathione (GSH) levels were lower in the infected group compared to the control group. There was a strong correlation between erythrocyte ARG activity and NO, MDA, TOS, OSI, TAS and GSH. ROC analysis and correlation results suggest that erythrocyte ARG activity is an effective oxidative stress marker. We concluded that severe oxidative stress occurs in anaplasmosis. As the severity of anaemia increases, erythrocyte ARG activity plummets while plasma NO level elevates. These two parameters may also be used as prognostic and oxidative stress markers. Although decreased erythrocyte ARG activity is a disadvantage in haemolytic diseases, this situation can be compensated by increased NO. Thus, homeostasis of these two parameters may contribute to the elimination of the infection.

Ramelteon and mechanism of its restorative effect in an experimental lung disease model

Methotrexate (MTX) is an anticancer agent widely used in clinical practice for various oncological, rheumatological, autoimmune, and inflammatory diseases. However, the side effects of MTX limit its usage for treatment. In addition, diffuse alveolar damage, interstitial pneumonia, fibrosis, and pleural reactions may be encountered in MTX-induced pulmonary toxicity. Ramelteon (RML), a melatonin receptor agonist, has antioxidant, anti-inflammatory, and protective effects are shown by several studies. This study aimed to show the antioxidant, anti-inflammatory, and antiapoptotic effects of RML and its effect on the airway surface liquid volume homeostasis via aquaporins (AQP) in MTX-induced lung injury. Thirty-two female Wistar Albino rats were grouped into four groups as control, MTX (20 mg/kg, intraperitoneally, a single dose), MTX + RML, and RML (10 mg/kg, via oral gavage, for seven days) groups. Once the experiment ended, the rats’ lung tissues were taken for biochemical, genetic, histopathological, and immunohistochemical examinations. MTX significantly increased oxidative stress index and total oxidative status, and decreased total antioxidant status levels by 202.0%, 141.4%, 20.2%, respectively, relative to the control (p ˂ 0.001 for all). AQP-1/5, which is an indicator of lung damage, was also found to decrease significantly (p ˂ 0.001). In addition, a significant increase was observed in interleukin-1β, interferon-beta, and caspase-8 expressions and histopathological changes as a result of immunohistochemical and histochemical examinations (p ˂ 0.001). RML treatment ameliorated all these changes and significantly regressed lung damage. Our results suggest that RML might be used as a lung-protective agent in various models of lung and tissue injury.

Expression of ER stress markers (GRP78 and PERK) in experimental nephrotoxicity induced by cisplatin and gentamicin: roles of inflammatory response and oxidative stress.

This study aimed to establish the relationship between two endoplasmic reticulum (ER) stress proteins, glucose-regulated protein 78 (GRP78/BiP) and PKR-like endoplasmic reticulum kinase (PERK), and oxidative stress markers in cisplatin (CIS)-induced and gentamicin (GEN)-induced nephrotoxicity.The study consisted of five groups: control (saline solution only), CIS D2 (2.5mg/kg for 2days), CIS D7 (2.5mg/kg for 7days), GEN D2 (160mg/kg for 2days), and GEN D7 (160mg/kg for 7days). All rats were sacrificed 24h after the last injection for standard clinical chemistry, and ultrastructural and histological evaluation of the kidney.CIS and GEN increased blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as total oxidant status (TOS), while decreasing total antioxidant status (TAS) level in CIS D7 and GEN D7 groups. Histopathological and ultrastructural findings were also consistent with renal tubular damage. In addition, expression of markers of renal inflammation (tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β)) and ER stress markers (GRP78 and PERK) was significantly increased in the kidney tissue of rats treated with CIS and GEN for 7days.These findings suggest that CIS and GEN administration for 7days aggravates nephrotoxicity through the enhancement of oxidative stress, inflammation, and ER stress-related markers. As a result, the recommended course of action is to utilize CIS and GEN as an immediate but brief induction therapy, stopping after 3days and switching to other drugs instead.

Investigation of the relationship between serum adropin levels, oxidative stress biomarkers, and blood pressure in DOCA-salt hypertensive rats

Background/Aim: Adropin is involved in the pathophysiology and development of cardiovascular diseases, such as hypertension. The aim of this study was to investigate the effects of adropin in serum, potential use as a biochemical biomarker of oxidative stress, and effects on blood pressure in deoxycorticosterone acetate (DOCA) salt hypertensive rats.
 Methods: Eighteen male Sprague-Dawley rats were divided into two groups: (1) Control (C) and (2) Hypertensive (H). Systolic and diastolic blood pressures (SBP and DBP, respectively), and mean blood pressure (MBP) were measured using the tail-cuff method. At the end of the study, serum endothelin-1 (ET-1), adropin, nitric oxide (NO), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were also analyzed.
 Results: Significant increases in SBP, DBP, MBP, cardiac hypertrophy index (CHI), and left ventricular hypertrophy index (LVCI) in the H group compared with the C group were found. Serum levels of ET-1, TOS, and OSI were significantly higher in the H group and serum levels of NO, adropin, and TAS were lower than in the C group. A negative correlation between serum adropin levels and the variables SBP, DBP, MBP, TOS, OSI, CHI, and LVHI was found. Adropin levels were positively correlated positively with serum NO levels in both groups.
 Conclusion: Serum adropin levels decreased in hypertensive DOCA-salt rats. Lower serum adropin levels were found to be significantly associated with hypertension and may play a role in this disease. However, further comprehensive and diverse studies are needed.

The Role of Reduced Glutathione on the Activity of Adenosine Deaminase, Antioxidative System, and Aluminum and Zinc Levels in Experimental Aluminum Toxicity.

Aluminum (Al) is one of the most abundant element in the world. But aluminum exposure and accumulation causes serious diseases, related with free radicals. Reduced glutathione (GSH) is a tripeptide with intracellular antioxidant effects. This study aimed to investigate the role of GSH on adenosine deaminase (ADA), antioxidant system, and aluminum and zinc (Zn) levels in acute aluminum toxicity. In this study, Sprague-Dawley rats (n = 32) were used. The rats were divided into four equal groups (n = 8). Group I received 0.5mL intraperitoneal injection of 0.9% saline solution (NaCI), Group II received single-dose AlCI3, Group III was given GSH for seven days, and Group IV was given AlCI3 single dose, and at the same time, 100mg/kg GSH was given for seven days. At the end of the trial, blood samples were collected by cardiac puncture. Serum total antioxidant status (TAS) and Zn levels were lower in the aluminum-administered group than the control group. In contrast, plasma total oxidant status (TOS) and aluminum concentrations and ADA activity were found higher in the aluminum-administered group than in the control group. Unlike the other groups, group GSH administrated with aluminum was similar to the control group. As a result, GSH administration has a regulatory effect on ADA activity, antioxidant system, and Zn levels in experimental aluminum toxicity. In addition, GSH may reduce the oxidant capacity increased by Al administration and may have a tolerant role on the accumulated serum Al levels. But long-term experimental Al toxicity studies are needed to reach a firm conclusion.

The effect of carvacrol on tramadol-induced oxidative renal injury in rats: biochemical and histopathological evaluation

Long-term treatment with tramadol is reported to be toxic to the kidneys. Research shows that tramadol reduces antioxidants and increases oxidants produced in renal tissue. This study aims to investigate the carvacrol effect on tramadol-induced renal injury in rats. The animals were divided into four groups: healthy (HG), individual tramadol (TR), individual carvacrol (CR), and tramadol + carvacrol (TC). Malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPO), superoxide dismutase (SOD), total oxidant status (TOS), total antioxidant status (TAS), blood urea nitrogen (BUN), and creatinine (Cr) were measured. Renal tissue was examined histopathologically. MDA, TOS, BUN, and Cr were significantly elevated in group TR and identified as low in group TC compared to group TR but higher than in the HG group. The tGSH, SOD, GPO, and TAS levels were low in group TR and higher in group TC than in group TR but lower than in the HG group. Histological examination of the TR group revealed diffuse necrosis and focal polymorphonuclear leukocytes (PMNLs) in the tubules. In the TC group, tubular atrophy and necrosis were minimal, and PMNL was rare. We observed that tramadol increases oxidants, decreases antioxidants, increases BUN and Cr, and examined whether the toxic effect on renal tissue regressed with carvacrol.

Evaluation of Malondialdehyde Level, Total Oxidant/Antioxidant Status and Oxidative Stress Index in Colorectal Cancer Patients.

Oxidative stress may play an important role in colorectal cancer (CRC). The present study included 94 adult patients with CRC (52 men and 42 women) and 26 hospitalized patients (12 men and 14 women) in whom CRC was excluded (control group). During hospitalization, blood serum samples were collected from both groups. Apart from that, anthropometric measurements were taken and other clinical data were analyzed. Serum malondialdehyde (MDA) level, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) were assayed. Subsequently, the relationship between the analyzed oxidative stress markers and selected clinical characteristics was investigated in both groups. The evaluation of oxidative stress marker values demonstrated that MDA and TAS levels were significantly higher in the control group than the CRC group (p < 0.001 and p = 0.019, respectively), while TOS levels were significantly higher in the CRC group than the control group (p = 0.005). Significantly lower OSI levels were found in the control group than in the CRC group (p < 0.001). Similar results can be observed when performing ROC analysis (receiver operating characteristic curve). Preliminary statistical analysis demonstrated that MDA levels in the study group depend on the location of the primary tumour (p = 0.035). Based on the post hoc Tukey test, a relationship was demonstrated between the MDA level and the left and right side of the colon (p = 0.040). The results may be evidence for a higher level of oxidative stress, including a compromised antioxidative defence system, in patients with CRC.

Oxidant/Antioxidant Status and Certain Trace Elements Relationship in Hair Goats Naturally Infected by Neospora caninum

This study was performed to determine the prevalence of Neospora caninum in female hair goats raised in different locations of the Siirt province of Turkey, and to investigate the total antioxidant status (TAS), total oxidant status (TOS), Zinc (Zn), and Copper (Cu) levels of the infected goats. The animal material of the study consists of a total of 184 female hair goats that are between 1 to 6 years old with the random sampling method. Investigation of the N.caninum antibodies was then performed using a commercial ELISA kit. The results of the ELISA tests reveal that the prevalence of N. caninum in the province of Siirt was 10.33% (19/184) positive, 7.61% (14/184) suspected, and 82.07% (151/184) negative. According to the ELISA test results, 10 seropositive and 10 seronegative sera samples were used in the TAS, TOS, Zn, and Cu analysis. The TAS (p&lt;0.01) and Zn (p&lt;0.001) levels of goats positive with N. caninum were found to be lower compared to those of the seronegative goats, while their TOS and Cu levels were higher (p&lt;0.05). This study was the first to determine the N.caninum prevalence in the goats raised in the province of Siirt. It was concluded that it would be beneficial to take precautionary measures, as well as further studies with larger scopes to be performed which should also involve dogs as the final hosts. Furthermore, the oxidative stress parameters (TAS, TOS) and certain trace elements (Zn, Cu) were found to be affected by the Neosporosis, which should be useful in the diagnosis and treatment of the disease.

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

Placental and Umbilical Cord Blood Oxidative Stress Level and Telomere Homeostasis in Early Onset Severe Preeclampsia.

Although the etiopathogenesis of preeclampsia (PE) is unknown, evidence suggests that it may be associated with increased oxidative stress. Studies have shown that oxidative stress can affect DNA fragments called telomeres. However, the interactions of PE, oxidative stress, and telomere length are not clearly known. This study aims to evaluate the oxidative/anti-oxidative stress balance in the placenta and umbilical cord and examine the effect of oxidative stress on telomeres. Cord blood and placental samples were collected from 27 pregnant women with severe PE (280/7-336/7 gestational weeks) and 53 healthy pregnant women. Telomere length (TL) was measured by real-time PCR in the cord blood and placenta tissue. Total antioxidant status (TAS) and total oxidant status (TOS) levels were measured in the cord blood and placenta tissue using a colorimetric method. No significant differences were found between groups regarding age, BMI, gravida, parity, and newborn gender (p>0.05). Cord blood and placental TL of PE patients were significantly shorter than the control group, while cord blood and placental TAS and TOS levels were higher (p<0.05). The results of a multivariate logistic regression analysis showed that the level of placental TOS in PE patients (OR=1.212, 95% CI=1.068-1.375) was an independent risk factor affecting PE. This study found that oxidative stress is an independent risk factor in the development of PE and shortens TL in both placental and umbilical cord blood. Future research on telomere homeostasis may offer a new perspective for the treatment of PE.

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.

Molecular docking to investigate the inhibitory activity and the role of nitric oxide in anticonvulsant effects of vitamin D on pentylenetetrazole‑induced epileptic seizures in rats

Despite the great breakthroughs in the field of epilepsy studies, the present drugs are ineffective in one-third of the patients, as well as without providing a definite treatment. There is accumulating evidence suggesting the role of vitamin D in epilepsy. The aim of this study was to investigate the effect of vitamin D on seizure formation, post-seizure cognitive functions, and the possible role of nitric oxide and oxidative stress in this effect, in the PTZ-induced seizure rat model. Sixty male Wistar albino rats were used in this study. The rats were randomly divided into 11 groups each containing 6 animals: Group 1: Control; Group 2: Saline+PTZ (45 mg/kg); Group 3: Vitamin D (1.5 mg/kg)+PTZ; Group 4: L-Arginine (500 mg/kg)+PTZ; Group 5: L-NAME (60 mg/kg)+PTZ; Group 6: 7-Nitroindazole (40 mg/kg); Group 7: Aminoguanidine (100 mg/kg)+PTZ; Group 8: Vitamin D+L- Arginine+PTZ; Group 9: Vitamin D+L-NAME+PTZ; Group 10: Vitamin D+7-Nitroindazole+PTZ; Group 11: Vitamin D+Aminoguanidine+PTZ. Animal behavior was evaluated with open field and passive avoidance tests. Nitric oxide (NO), total oxidative status (TOS), and total antioxidant status (TAS) levels in the cortex and hippocampus brain regions were determined by ELISA method. The treatment of vitamin D in combination with NO inhibitors has a positive effect on the PTZ-induced seizures and ameliorate post-seizure learning deficits. Moreover, the combination of vitamin D with NO inhibitors reduced oxidative stress and NO levels after seizures in the cortex and hippocampus. Also, we employed molecular docking and density functional theory analysis to investigate the inhibitory activity, reactivity, and stability of Vitamin D with other NO inhibitors. Vitamin D supplementation could be effective as a supportive treatment drug in epileptic patients, according to the findings.

Suppression of cisplatin-induced ovarian injury in rats by chrysin: an experimental study

The aim of this study was to investigate the potential therapeutic efficacy of chrysin (CHS) against ovotoxicity caused by intraperitoneal administration of cisplatin (CDDP) in rats. In this experimental study, 24 female rats were randomly divided into four groups: control, CHS (2 mg/kg), CDDP (5 mg/kg) and CDDP (5 mg/kg) + CHS (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), interleukin-6 (IL-6) and myeloperoxidase (MPO) were determined in the ovarian tissues using spectrophotometric methods. In addition, the ovarian samples were evaluated histopathologically by hematoxylin&eosin staining. The results revealed that the levels of MDA, TOS, IL-6 and MPO significantly increased by CDDP administration compared with control group (p < 0.05). Also, it was found that CDDP significantly decreased TAS and SOD levels (p < 0.05). CHS ameliorated CDDP-induced the increased levels of MDA, TOS, IL-6, MPO and increased the levels of TAS and SOD significantly (p < 0.05). Histological findings also supported the therapeutic effect of CHS against CDDP-induced ovarian damage parameters. In conclusion, our results showed that CHS exhibits a therapeutic effect against CDDP-induced ovotoxicity and therefore the use of CHS after chemotherapy may improve the side effets of CDDP. IMPACT STATEMENT What is already known about this subject? Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited due to dose-related tissue toxicity. Chrysin (CHS), a natural flavone, exhibits various beneficial activities, including antioxidant, anti-inflammatory and anticancer. There are increasing evidences in the literature that CHS reduces the toxicity of various chemotherapeutic agents, such as CDDP, doxorubicin and cyclophosphamide, in colon, kidney and liver tissues through its antioxidant and anti-inflammatory potential. What do the results of this study add? This study demonstrated that CHS can abolish CDDP-induced in vivo ovarian injury by decreasing MDA, TOS, IL-6 and MPO levels and increasing SOD and TAS levels through its antioxidant and anti-inflammatory potential. What are the implications of these findings for clinical practice and/or further research? This study revealed the therapeutic potential of CHS against CDDP-induced acute ovotoxicity, for the first time. Further pre-clinical studies are necessary to prove the beneficial effect of CHS on the prevention of CDDP-induced ovarian toxicity.

Ameliorating effects of ramelteon on oxidative stress, inflammation, apoptosis, and autophagy markers in methotrexate-induced cerebral toxicity.

Objective(s):Methotrexate (MTX) is a widely used chemotherapeutic agent that, however, is known to have serious side effects such as neurotoxicity. In the present study, we aimed to evaluate the possible favorable effects of ramelteon (RMLT) on MTX-induced cerebral toxicity. Materials and Methods:Thirty-two male Wistar albino rats were divided into four groups: Control group, MTX group (20 mg/kg MTX, IP, single dose), MTX+RMLT group (20 mg/kg MTX, IP, single dose + 10 mg/kg RMLT, by gavage, 7 days), and RMLT group (10 mg/kg RMLT, by gavage, 7 days). Results: In the MTX group, increased levels of total oxidant status (TOS) and oxidative stress index (OSI) levels and decreased levels of total antioxidant status (TAS) level were observed. RMLT significantly reversed oxidative stress parameters. Real-time PCR analysis revealed that MTX increased the expressions of Beclin-1 and autophagy-related gene 12 (ATG12). These expressions were significantly decreased by RMLT. Vacuolar changes, apoptotic cells, and inflammatory cell infiltration induced by MTX were ameliorated by RMLT treatment. Increased tumor necrosis factor-α (TNF- α) and Caspase-3 activities induced by MTX were returned to their normal levels by RMLT. Conclusion:All our results demonstrate that RMLT alleviates the harmful effects of MTX on the cerebral cortex tissue. Therefore, RMLT may be considered for supportive therapy for preventing side effects of MTX in patients needing MTX therapy.

SERUM TOTAL OXIDANT AND ANTIOXIDANT STATUS IN CHILDREN WITH CANCER

Oxidative stress has a potential role in carcinogenesis. Antioxidant enzymes have neutralizing effect both on cancer initiation, and progression. We aimed to assess the oxidant and antioxidant levels of pediatric cancer patients and to compare the levels in healthy controls. The study involved 105 pediatric cancer patients (40 undergoing chemotherapy, 65 survivors) and 40 healthy children. The serum total oxidant status (TOS) and total antioxidant status (TAS) were measured. The TOS and oxidative stress index were lower in pediatric cancer patients compared to the levels in the controls (3.73±1.35 vs. 4.21±1.72 µmol/L; p=0.08; 0.20±0.07 vs. 0.26±0.10; p=0.001, respectively). The mean serum TAS level was higher in patient groups compared to the level in the control (1.87±0.48 vs. 1.63±0.32 mmol/L, p=0.001). The TAS level of children with cancer in survivors was still found to be significantly higher compared to the levels in the control group (1.85±0.45 vs. 1.63±0.32 mmol/L, p=0.005). Radiotherapy, surgery, relapsed disease, presence of metastases and receiving enteral nutritional support caused no change in the TAS/TOS level. It has been revealed for the first time that the serum total antioxidant level increased during cancer treatment and didn't normalize after cessation of therapy for a long time.

The Anti-Inflammatory and Antioxidant Effects of Propofol and Sevoflurane in Children With Cyanotic Congenital Heart Disease

The authors aimed to compare the anti-inflammatory and antioxidant effects of propofol and sevoflurane in children with cyanotic congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass. Prospective, randomized, double-blind study. Single center, university hospital. Children ages 1-10 years with CCHD undergoing elective cardiac surgery with cardiopulmonary bypass. Children were randomized to receive general anesthesia with either sevoflurane (group S) or propofol (group P). Systemic inflammatory response syndrome (SIRS) occurrence was assessed at the end of the surgery and at the sixth, 12th, and 24th postoperative hours. Blood samples were obtained at 4 times: after anesthesia induction (T0), after release of the aortic cross-clamp (T1), at the end of the surgery (T2), and at the postoperative 24th hour (T3). The serum levels of interleukin 6 and tumor necrosis factor alpha, and the total antioxidant status (TAS) and total oxidant status, were analyzed. SIRS was more common in group S than in group P at all times (p=0.020, p=0.036, p=0.004, p=0.008). There were no significant differences between the groups in the mean tumor necrosis factor alpha and interleukin 6 levels at any time. The TAS level at T2 was higher in group P than group S (p=0.036). The serum TAS level increased at T2 compared with T0 in group P, but it decreased in group S (p=0.041). The results showed that propofol provided a greater antioxidant effect and reduced SIRS postoperatively more than sevoflurane in children with CCHD undergoing cardiac surgery.

Relationship between Selected Micronutrient Concentrations, Total Antioxidant Status, Pain Severity, and the Image of 1H MR Spectroscopy in Degenerative Spine Disease: A Case-Control Study.

Osteoarthritis of the spine is a common disease and constitutes a significant problem in highly developed countries. Due to the aging of the population, the number of patients with advanced degenerative changes continues to grow. Trace elements and antioxidant status may play an active role in the pathogenesis of osteoarthritis of the spine. The aim of this study was to assess the relationship between total antioxidant status (TAS), the concentration of selected elements (Zn, Cu, Se, Mn) in the serum, nutritional and environmental factors, the severity of pain, and images of degenerative changes in the spine demonstrated in proton magnetic resonance spectroscopy (1H MRS). The study included 90 patients with degenerative spine disease and 40 healthy people. Serum Zn, Cu, Se, and Mn concentrations were determined by atomic absorption spectrometry. The Cu/Zn molar ratio was calculated. TAS was determined spectrophotometrically using a ready-made Randox kit. The severity of spine pain was assessed using the visual analogue scale VAS. In the 1H MRS study, the fat/water ratio was determined in L1 and L5 vertebral bodies and in the L4/5 intervertebral disc. In patients with osteoarthritis of the spine, there was a reduced concentration of Zn and Cu in the serum (0.77 ± 0.22 mg/L, 1.1 ± 0.35 mg/L) compared to the control group (0.83 ± 0.13 mg/L, 1.25 ± 0.41 mg/L, respectively). In the study group, we also observed a significantly lower Cu concentration in smokers (1.07 ± 0.35 mg/L) compared to non-smokers (1.17 ± 0.34 mg/L). A relationship between the female sex and a decreased concentration of TAS in the serum, both in people with degenerative spine disease and in healthy people, has been demonstrated. In patients with serum TAS levels below the reference values, the fat/water ratio was higher in the L5 spine shaft, while in those with elevated Mn levels, the value was higher in the L4/L5 intervertebral disc, which indicates a greater degree of degeneration in both cases. Patients with normal serum Cu concentration experienced lower pain intensity assessed in the VAS scale. The study showed some abnormalities in serum trace element levels and TAS in patients with osteoarthritis of the spine.

The protective effect of carvacrol on bevacizumab-related skin injury in rats: a biochemical and histopathological evaluation

Purpose Bevacizumab is a recombinant humanized monoclonal antibody that specifically binds to vascular endothelial growth factor (VEGF). Cutaneous side effects of bevacizumab are seen with substantial frequency and may require the interruption of the treatment. The aim of the study was to conduct a biochemical and histopathological investigation of the effects of carvacrol against the possible oxidative skin damage caused by bevacizumab in rats. Materials and methods A total of 18 adult male Wistar albino rats were randomly assigned to three groups as healthy (H group; n = 6), bevacizumab alone (B group; n = 6), and carvacrol + bevacizumab (CB group; n = 6). Carvacrol was injected intraperitoneally (IP) at a dose of 50 mg/kg in the CB group. Sterile salt solution (0.9% NaCl) was used as a solvent for the H and B groups. One hour after the administration of carvacrol and solvent, bevacizumab at a dose of 10 mg/kg IP was administered to the CB and B groups. Bevacizumab was given once daily for a total of two doses, 15 days apart. Carvacrol was administered once daily for one month. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPO), catalase (CAT), superoxide dismutase (SOD), total oxidant status (TOS), and total antioxidant status (TAS) levels in rats’ skin tissues were biochemically evaluated. The parameters were measured with spectrophotometric method by using a microplate reader (BioTek, Winooski, VT, USA). The skin tissues were also examined histopathologically by the pathologist (blind) for the study groups. Results The MDA and TOS levels of the H and CB groups were significantly lower than the B group (p < 0.05). The mean scores of the other biochemical levels (GSH, GPO, CAT, SOD, TAS) in the H group were significantly higher than in the B and CB groups. Pathological examination of H group was normal. In B group epidermal atrophy, abnormal keratin accumulation, degenerated hair follicles, edoema and inflammatory cells accumulation in the dermis were observed. In the CB group, these findings were significantly improved. Conclusion The positive effect of carvacrol against possible local oxidative skin damage due to bevacizumab in rats was demonstrated. In addition, more detailed studies are required to clarify the mechanism of the protective effect of carvacrol against bevacizumab-induced skin toxicity. The effect should be evaluated through further human studies, as well as studies using different doses of carvacrol.

Sex-Specific Association between Antioxidant Defense System and Therapeutic Response to Risperidone in Schizophrenia: A Prospective Longitudinal Study.

There are various differences in response to different antipsychotics and antioxidant defense systems (ADS) by sex. Previous studies have shown that several ADS enzymes are closely related to the treatment response of patients with antipsychotics-naïve first-episode (ANFE) schizophrenia. Therefore, the main goal of this study was to assess the sex difference in the relationship between changes in ADS enzyme activities and risperidone response. The plasma activities of glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and total antioxidant status (TAS) were measured in 218 patients and 125 healthy controls. Patients were treated with risperidone for 3 months, and we measured PANSS for psychopathological symptoms and ADS biomarkers at baseline and at the end of 3 months of treatment. We compared sex-specific group differences between 50 non-responders and 168 responders at baseline and at the end of the three months of treatment. We found that female patients responded better to risperidone treatment than male patients. At baseline and 3-month follow-up, there were no significant sex differences in TAS levels and three ADS enzyme activities. Interestingly, only in female patients, after 12 weeks of risperidone treatment, the GPx activity of responders was higher than that of non-responders. These results indicate that after treatment with risperidone, changes in GPx activity were associated with treatment response, suggesting that changes in GPx may be a predictor of response to risperidone treatment in female patients with ANFE schizophrenia.