Dative Stress Research Articles

The protective effect of Curcuma longa on male infertility induced by thioacetamide

Objective: This study aimed to investigate the impact of thioacetamide (TAA) on the structure and function of the testes and assess the therapeutic effects of Curcuma longa (Cl) against TAA-induced toxicity in rats. Materials and Methods: Thirty-two male albino rats weighing 180–200 gm and aged 11–12 weeks were randomly separated into four groups. The control group was given normal saline, the Cl group was orally administered Cl (500 mg/kg/day), the TAA group received intraperitoneal TAA (200 mg/kg body weight, three times/week), and the Cl with TAA group received Cl orally two hours before TAA administration. After 8 weeks, all rats were anesthetized, and body and testis weights were recorded. Morphological and histological assessments as well as biochemical analyses were conducted. Results: The study revealed a significant decrease in both body and testis weights in the TAA group, accompanied by a substantial increase in luteinizing hormone (LH), follicle-stimulating hor¬mone (FSH), and malondialdehyde (MDA) levels. Testosterone (T) and glutathione (GSH) were significantly decreased in the TAA-treated group compared to the control. Conversely, the Cl-treated group exhibited a substantial decrease in LH, FSH, and MDA levels while showing a significant increase in T and GSH. Conclusion: Cl has been found to have a potential therapeutic role in mitigating TAA-induced testicular damage by acting as an antioxidant. This is supported by a significant decrease in oxi¬dative stress markers and supporting hormonal levels. Further research is needed to understand the underlying mechanisms and explore the clinical applicability of Cl in preventing and treating testicular toxicity.

Post-transcriptional regulation of redox homeostasis by the small RNA SHOxi in haloarchaea

ABSTRACT While haloarchaea are highly resistant to oxidative stress, a comprehensive understanding of the processes regulating this remarkable response is lacking. Oxidative stress-responsive small non-coding RNAs (sRNAs) have been reported in the model archaeon, Haloferax volcanii, but targets and mechanisms have not been elucidated. Using a combination of high throughput and reverse molecular genetic approaches, we elucidated the functional role of the most up-regulated intergenic sRNA during oxidative stress in H. volcanii, named S mall RNA in H aloferax Oxi dative Stress (SHOxi). SHOxi was predicted to form a stable secondary structure with a conserved stem-loop region as the potential binding site for trans-targets. NAD-dependent malic enzyme mRNA, identified as a putative target of SHOxi, interacted directly with a putative ‘seed’ region within the predicted stem loop of SHOxi. Malic enzyme catalyzes the oxidative decarboxylation of malate into pyruvate using NAD+ as a cofactor. The destabilization of malic enzyme mRNA, and the decrease in the NAD+/NADH ratio, resulting from the direct RNA–RNA interaction between SHOxi and its trans-target was essential for the survival of H. volcanii to oxidative stress. These findings indicate that SHOxi likely regulates redox homoeostasis during oxidative stress by the post-transcriptional destabilization of malic enzyme mRNA. SHOxi-mediated regulation provides evidence that the fine-tuning of metabolic cofactors could be a core strategy to mitigate damage from oxidative stress and confer resistance. This study is the first to establish the regulatory effects of sRNAs on mRNAs during the oxidative stress response in Archaea.

Analysis of Level of Antioxidants and Oxidative Stress in Diabetic Patients

Background and objectives: Diabetes mellitus is a metabolic disorder whose prevalence is rising rapidly in an alarming rate. The main objective of the study is to analyse the level of antioxidants and oxidative stress in diabetic patients among local population of Pakistan. Material and methods: This cross sectional study was conducted in Department of Pathology, Islamic International Medical College Rawalpindi during March 2019 to November 2019. For this purpose we selected the patients who were suffering from diabetes. The data was collected from 100 patients who visited the OPD of the hospital. This study is based on the local population of Pakistan, which shows the stress level in diabetic patients. Results: The data was collected from 100 patients. According to analysis of data level of antioxidant and oxidative stress is increasing in diabetic patients because cell becomes destroyed. GSH is important non-enzymatic antioxidant which helps in scavenging of free radical mechanism. According to data the levels of GSH become decreases in diabetic patients. The data pertaining in the table shows that levels of sialic acid become increases in patients. Conclusion: It is concluded that level of antioxidants in our body plays an important role. It is obvious from the presented data that a relation exists between hyperglycaemia, oxidative stress, cellular and endothelial dysfunction.

Pilot Study of Biomarkers of Oxidative Stress and Chlamydia trachomatis in Female Patients with Spontaneous Abortions

The aims of the present study were i. asses the biomarkers of oxi- dative stress including superoxide anion radical, Nitrite measurement and reduced glutathione in female patients with spontaneous abortions Asses the prevalence of C. trachomatis antibodies IgA and IgG in those patients, iii. Correlate the levels of the oxidative biomarkers to the presence of C. trachomatis antibodies. The study included one hundred female patients with 2 or more spon- taneous abortions in addition to one hundred healthy control females with normal gravidity and parity history. Blood samples were obtained from each subject and subjected to laboratory determination of super- oxide anion radical, Nitrite measurement and reduced glutathione by biochemical methods. Determination of specific immunoglobulin A and G (IgA, IgG) was determined by enzyme linked immunosorbent assay (ELISA). The prevalence of IgA and IgG for C. trachomatis in patients was 4% and 8% respectively and, in the control, subjects the prevalence of IgA and IgG were 1% and 2% respectively. The concentration of oxidative stress products was significantly higher in the patients group compared to the control group (P=0.0001). The concentrations of nitrite and reduced glutathione were 27.9± 4.7, 31.4± 1.9 nmol/ml respectively in patients and the concentrations of nitrite and reduced glutathione were 18.9± 2.1 and 27.9± 3.9 respectively in the control group. The concentration of SOD was significantly reduced in the patients group compared to the control group (P=0.0001). The concentration of SOD was 55.1 6.9 in the patients and in the control the concentration was 64.5± 7.7 nmol/ml In the study of oxidative stress markers in the patients with positive serology for C. trachomatis, there was significant increase in nitrite concentrations compared to patients negative for C. trachomatis sero- logical markers (P=0.005). While reduced glutathione concentration had insignificant increase in patients positive for C. trachomatis with reduced SOD compared to patients with negative serology to C. tra- chomatis, P=0.6, P=0.07, respectively. The present study highlights that there was significant increase in oxi- dant stress biomarkers nitrite and reduced glutathione with significant reduction in superoxide dismutase in patients with repeated abortions. The prevalence of IgG to C. trachomatis was significantly prevalent in patients with recurrent abortion compared to control subjects. The nitrite was significantly correlated with positive serology to C. tracho- matis.

Effects of alpha-ketoglutarate on lifespan and functional aging of Drosophila melanogaster flies

The effects of an alpha-ketoglutarate-supplemented diet on lifespan and functional senescence were evaluated in the Canton S strain of Drosophila melanogaster. The results suggest that effects of dietary alpha-ketoglutarate (AKG) are dose-and gender-dependent. In males, diets containing 1-10 mM AKG did not affect mean and maximum lifespans, except that an increased maximum lifespan observed at 10 mM AKG. Diet with 20 mM AKG shortened median lifespan and had no effect on maximum lifespan of males. In females, diets with low concentrations of AKG (1 and 5 mM) did not affect lifespan, whereas diets supplemented with 10 and 20 mM AKG increased both median and maximum lifespans. At a lifespan-prolonging concentration (10 mM), AKG decreased fecundity, increased cold resistance and had no effect on climbing activity or resistance to oxi dative stress in flies of either gender at middle (24 days) and old (40 days) ages. Moreover, middle-aged AKG-fed females but not males were more resistant to heat stress that was accompanied by higher levels of HSP90 protein as compared with controls. Middle-aged flies on AKG-supplemented diets showed elevated oxidative stress and had higher total protein and triacylglycerol levels as compared with controls. Hence, anti-aging effects of AKG do not seem to be related to preventing oxidative stress development but involve metabolic rearrangement and synthesis of specific protective proteins, which aid to resist destructive processes with age.

Extrathoracic negative pressure ameliorates lung injury during mechanical ventilation in experimental pigs.

Mechanical ventilation (MV) is a supportive and life-saving therapy, however, it can cause ventilator-induced lung injury as a common complication. Thus, recruitment manoeuvres (RM) are applied to open the collapsed alveoli to ensure sufficient alveolar surface area for gas exchange. In the light of the fact that positive pressure ventilation is currently the standard treat- ment for improving pulmonary function, extrathoracic negative pressure is considered as an alter- native form of respiratory support. The aim of this study was to estimate the proinflammatory and oxidative response during MV and lung injury as well as the response after RM. All studied parameters were assessed at the following time points: T1-spontaneous breathing, T2- MV, T3- lung injury, T4 -RM. During MV (T2) elastase, MPO, ALP release, nitrite and superoxide generation significantly increased, whereas in later measurements a decrease in these values was noted. The MDA plasma concentration significantly (p⟨0.05) increased at T2, reaching a level of 13.30±0.87 nmol/ml; at other time points the values obtained were similar to the baseline value of 9.94±0.94 nmol/ml, whereas a gradual decrease in SOD activity at time T2-T4 points in comparison with the baseline value was found. During the study both neutrophil activity and oxi- dative stress indicate exacerbated response after MV and lung injury by bronchoalveolar lavage; however, extrathoracic negative pressure system as the MR ameliorates damaging changes which could further lead to serious lung injury.

Chemical and Biological Activities of Some Scorzonera Species: An In Vitro Study

The present study was carried out on the phy- tochemical composition (total flavonoids and total poly- phenols), antioxidant activity and antimicrobial effect of the Scorzonera suberosa (C. Koch), Scorzonera latifolia (Fisch. and Mey.) and Scorzonera laciniata (L.). Total flavonoid and polyphenol contents of the species were determined using spectrophotometric methods. Effect of scavenging ABTS and DPPH free radical of species was compared with that of butylated hydroxytoluene. The antimicrobial effect of plant extracts was determined by the method of agar well diffusion. Additionally, after the oxi- dative stress induced by hydrogen peroxide, the effect of plant extracts on lipid peroxidation, protein and glutathione levels was determined in the yeast culture. As the result, plant extracts showed high antioxidant and antiradical effects. All plant samples had more pronounced antimi- crobial effect on Escherichia coli and Bacillus megaterium. In addition, these samples showed antitoxic property and protective effect of cell viability in the probiotic yeast culture.

Possible Modulating Effects of Celecoxib (COX II Inhibitor) on Antide-pressant Action of Duloxetine (SNRI) in Stressed Mice

Rationale: In recent years, a potential link between inflammation and depression has been shown and the role of proinflammatory cytokines in the pathophysiology of major depressive disorders has been observed. Celecoxib (selective COX-II inhibitor) has been reported to inhibit the production of PGE-II and proinflammatory cytokines and also increase tryptophan levels and serotonin availability in depressed patients. On the other hand, duloxetine (potent SNRI) has been shown to be efficacious in inflammatory and acute pain models in rodents and synergistic interaction with NSAIDs. How- ever, the interactions of duloxetine with celecoxib are currently unknown. Objective: We evaluated the antidepressant effect of celecoxib (15, 30 mg/kg/day for 15 days, ip) alone and in combina- tion with duloxetine (5, 10 mg/kg/day for 15 days, ip) and also the biochemical parameters in stressed mice. Results: Pretreatment of celecoxib (15, 30 mg/kg) for 15 days to forced swim-induced stressed mice produced significant antidepressant effect which has been evidenced by decreased in immobility time in tail suspension test (TST). Celecoxib (30 mg/kg) also showed significant increase in locomotor activity and protective effect on biochemical parameters of oxi- dative stress by reversing stress-induced increase in TBARS and reduction in GSH levels. Pretreatment with combination of celecoxib with duloxetine (5, 10 mg/kg) showed significant antidepressant and neuroprotective effects against stress in- duced depression and oxidative damage in mice at both dose levels. Conclusions: This study demonstrated dose-dependent antidepressant action of celecoxib in stressed mice. The combina- tion of celecoxib with duloxetine further enhanced its antidepressant effect on TST in stressed mice. The treatment re- versed forced swim-induced elevation in TBARS levels and depleted glutathione activity, suggesting their antioxidant and protective role in brain.

Pathophysiological roles and the molecular mechanism of mitochondria in neuronal calcium regulation

Calcium is an important signaling molecule involved in the regulation of many physiological as well as pathological cellular responses. Especially, the spatiotemporal pattern of local calcium signaling is critical for the specificity of cellular responses. We reviewed here pathophysiol0gical roles and the molecular mechanism of mitochondria as well as endoplasmic reticulum (ER) in neuronal calcium regulation. The Iiving cells evoke calcium influx outside the cells and also induce calcium release from ER in response to many stimuli. However, severe and sustained calcium release from ER induces calcium uptake into mitochondria. Pathologically elevated mitochondrial calcium responses are accompanied by mitochondria depolarization. mitochondria permeability transition pore (mtPTP) opining and subsequent mitochondria-dependent apoptosis. Ratiometric realtime measurements of intramitochondrial local Ca suggest that high mitochondrial Ca2+ is the crucial factor determinating whether cells : undergo apoptosis. On the other hand, calcium depletion in ER also induces ER stress which evokes protein folding defects and ER stress-dependent apoptosis. The recent growing body of evidence on pathophysiological roles and the molecular mechanism of mitochondria as well as ER could provide an insight for the development of new drug to treat neurodegenerative diseases in which pathogenesis either calcium overload or oxidative dative stress is involved.

Sleep Duration and Oxidative Stress: The Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) Study

Our objective was to investigate the cross-sectional association between sleep duration and biomarkers of oxi- dative stress (glutathione (GSH), glutathione peroxidase (GSH-Px), vitamin C, thiobarbituric acid reactive substances (TBARS), and trolox equivalent antioxidant capacity (TEAC)) among police officers. Standardized techniques were used to analyze biomarkers in fasting blood specimens. Mean levels of biomarkers were compared across levels of sleep dura- tion (0-4.9, 5.0-6.9, � 7.0 hours) using ANOVA. Officers' (women=44; men=69) mean age was 39.6 years. Positive trends were observed across sleep categories with mean levels of GSH and vitamin C only among women (p trend=0.156 and 0.022 respectively), with attenuation after risk-factor adjustment. Positive trends were observed for vitamin C among older officers (p trend=0.018) but not younger. No associations were observed between sleep duration and biomarkers among men. Longer sleep duration is associated with higher levels of vitamin C among policewomen and older officers. Additional studies are warranted.

Evidence for Oxidative Stress Damage Following High Intensity Anaerobic Performance

The purpose of this study was to compare power outputs, and blood concentrations of lipid hydroperoxides (LH), malondialdehyde (MDA) and lactate ((La - ) B ) following 30s of maximal cycle ergometry when resistive forces were derived from total-body mass (TBM) or fat-free mass (FFM). Differences (P < 0.05) in peak power output (PPO), pedal velocity (PV) and resistive forces (RF) were observed when the TBM and FFM protocols were compared (953 ± 114 W vs 1020 ± 134 W ; 134 ± 8 rpm vs 141 ± 7 rpm ; 6 ± 1 kg vs 5 ± 1 kg respectively). LH and MDA concentrations increased immediately post exercise during the TBM protocol only (P < 0.05) and decreased 24 h post exercise. Alpha- tocopherol and uric acid concentrations decreased immediately post exercise for both protocols (P < 0.05) and increased 24 h later (P < 0.05). The results of the study suggest that greater power outputs are obtainable with significantly less oxi- dative stress when resistive forces reflect FFM as opposed to TBM.

Contribution of Glutathione Peroxidase and Nitric Oxide to Potassium Bromate-Induced Oxidative Stress and Kidney Damage in Mice.

dative stress and kidney damage. However, no effect of L-NMMA was observed on the KBrO3-induced reduction of cytoplasmic GPx activity. These results suggest that reduction of cytoplasmic GPx activity resulted from the KBrO3 administration initiates oxidative stress and that NO also participates in the promotion of KBrO3-induced oxidative stress and kidney damage.

Partial Liquid Ventilation (PLV) Reduces Pulmonary Leukostasis in a Model of Acute Lung Injury (ALI). ♦ 212

PLV appears to attenuate the inflammatory response in various models of ALI as evidenced by histology. We have previously shown that PLV decreases free radical release by alveolar macrophages and attenuates oxidative damage to the lung. In view of the neutrophil's central role in the evolution of ALI, we hypothesized that PLV would reduce neutrophil influx to the lung and attenuate systemic inflammation in a model of ALI. 26 NZW rabbits were anesthetized and instrumented with a tra- cheostomy and vascular catheters. Animals were randomly assigned to either PLV with perflubron (LiquiVent®, Alliance Pharmaceutical) or control groups and were ventilated with FiO2= 1.0, and Ve required to obtain normal pCO2. Thirty minutes after onset of ventilation, animals were given 0.9mg/kg of E.coli endotoxin (F583, Sigma) IV. PLV or conventional ventilation was continued for another 5 h before sacrifice. Lungs were removed and frozen at -70°. Representative samples were stained for histology. Neutrophil count per high power field(hpf) was performed in 5 fields per sam- ple. Lung samples were homogenized in triplicate in PBS, ultrasonified, freeze-thawed and clarified. Supernatants were analyzed for MPO activity by spectrophotometry. As a measure of systemic oxi- dative stress, plasma samples from baseline (BL) and 5 h were assayed for oxidative buffer capacity (OBC) by chemiluminescence. Statistical analysis was performed using the Mann-Whitney U Test. Table