Thiol Levels Research Articles

Darbepoetin alpha has an anxiolytic and anti-neuroinflammatory effect in male rats

AimsWe aimed to investigate the anxiolytic effect of darbepoetin alpha (DEPO), an erythropoietin derivative, in a neuroinflammation model regarding different behaviors and biological pathways.MethodsForty adult male Wistar albino rats were divided into four groups (control, LPS, DEPO, and DEPO + LPS). The rats were treated with 5 µg /kg DEPO once a week for four weeks, after which neuroinflammation was induced with 2 mg/kg lipopolysaccharide (LPS). The elevated plus maze, open-field, and light‒dark box tests were conducted to assess anxiety levels. Harderian gland secretions were scored via observation. Tumor necrosis factor alpha (TNF-α), Interleukin-1-beta (IL-1β), brain-derived growth factor (BDNF), serotonin, cortisol, total antioxidant/oxidant (TAS/TOS), and total/free thiol levels were measured in the prefrontal cortex, striatum, and serum.ResultsDEPO had a potent anxiolytic effect on both DEPO and DEPO + LPS groups. Compared to the control group, DEPO administration caused an increase in serotonin and BDNF levels and decreased basal cortisol and TNF-α levels in naive rats. IL-1β did not alter after DEPO administration in naive rats. Prophylactic DEPO treatment remarkably downregulated cortisol, IL-1β, and TNF-α in the DEPO + LPS group. In addition, prophylactic DEPO administration significantly attenuated the decrease in serotonin and BDNF levels in the DEPO + LPS group. Furthermore, DEPO ameliorated excessive harderian gland secretion in the DEPO + LPS group. Compared with those in the control group, the free thiol content in the serum increased after DEPO administration. No similar effect was seen in the DEPO + LPS group receiving prophylactic DEPO. TAS showed no difference among all experimental groups. DEPO administration increased TOS and OSI in the serum and prefrontal cortex but not in the striatum. This effect was not seen in the DEPO + LPS group.ConclusionDarbepoetin alpha had an anxiolytic effect on many physiological mechanisms in a neuroinflammation model and naive rats.

The effects of dexmedetomidine on thiol/disulphide homeostasis in coronary artery bypass surgery: a randomized controlled trial

BackgroundThiol-disulfide homeostasis (TDH) plays a pivotal role in various physiological mechanisms, including antioxidant defence, detoxification, apoptosis, regulation of enzyme activities and cellular signal transduction. TDH can be used as a biomarker to detect oxidative stress (OS) levels and ischemia status in the tissues. Coronary artery bypass grafting (CABG) surgery is a procedure associated with high oxidative stress. Dexmedetomidine, an alpha-2 agonist anaesthetic agent, has antioxidant effects. In this study, the effects of dexmedetomidine on oxidative stress in CABG surgery were investigated.MethodsPatients who underwent on-pump CABG surgery were divided into two groups: those receiving dexmedetomidine (Group D) and those not receiving dexmedetomidine (Group C). From anesthesia induction to the end of surgery, patients in Group D received intravenous infusions of 0.05–0.2 mcg/kg/min remifentanil and 0.2–0.7 mcg/kg/h dexmedetomidine. Patients in Group C received intravenous infusion of 0.05–0.2 mcg/kg/min remifentanil. Blood samples were collected from the patients 30 min before induction of anesthesia (T1), 30 min after removal of the aortic cross-clamp (T2), and at the end of the surgery (T3). Thiol-disulfide homeostasis (TDH) was assessed using a novel method. A novel automated method enables the determination of native thiols, total thiols and disulfides levels in plasma, allowing the calculation of their respective ratios.ResultsIn patients receiving dexmedetomidine, lower postoperative levels of disulfide, disulfide/native thiol, and disulfide/total thiol, along with higher native thiol/total thiol, were observed compared to the control group. (p < 0.05) Postoperative native thiol and total thiol levels were similar for both groups. (p > 0.05)ConclusionsIn our study, through dynamic thiol-disulfide measurements, we found that levels of oxidative stress (OS) were lower in patients who received dexmedetomidine. We believe that the positive effects of dexmedetomidine on OS could be beneficial in CABG surgery. Furthermore, we anticipate that with further studies conducted in larger patient cohorts, the clinical utilization of dexmedetomidine will become more widespread.Trial registration numberNCT05895331 / 06.07.2023.

Relação entre estresse oxidativo e COVID-19: uma breve revisão sistemática

OBJECTIVE: Analyse the possible relationship between Oxidative Stress (OS) and the pathogenesis of COVID-19. METHODS: This brief systematic literature review was conducted based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The search resulted in the selection of 10 papers that met the research theme and were published between January 2020 and March 2021. RESULTS: The results revealed that in the course of the disease, there is a decrease in thiol levels and an increase in disulfide and EO, with a probable depletion of antioxidant elements. They found that the accumulation of Reactive Oxygen Species (ROS), added to the damage to albumin, were related to a worse prognosis and that neutrophils may be responsible for the increased level of oxidative stress associated with the worsening of the clinical condition. In addition, cells transfected with the SARS-CoV-2 spike protein showed around three times the concentration of ROS compared to non-transfected control cells. As for serum O2- levels, they were significantly elevated in critically ill patients, constituting a probable predictor of disease severity. CONCLUSIONS: Thus, from the findings of this study, it is possible to infer that both patients with severe and moderate forms of COVID-19 have high EO index values. However, further studies need to be carried out to confirm these preliminary results.

Evaluation of thiol/disulphide and oxidant-antioxidant status of dairy cows in periparturient and post-partum period.

Thiol/disulphide homeostasis (TDH) has a critical role in many cellular activities such as antioxidant protection. Alterations of oxidative stress in the transition period play an important role in development of some diseases and disorders in dairy cows. The purpose of this study is to assess the total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), total thiol, native thiol, disulphide and lipid profile in Simmental and Montofon dairy cows (aged 2-3) before and after calving. Blood samples were collected 233-280 days of pregnancy and the 30 days of post-partum. Serum total thiol, native thiol and disulphide levels were determined as well as TAS, TOS and paraoxonase-1 (PON-1) levels were measured using colorimetric assays. Triglycerides (TG), total cholesterol, HDL cholesterol and LDL cholesterol levels were measured with an automatic analyser. Total thiol (p=0.038) and disulphide (p=0.015) levels were higher after calving compare to pregnancy in Montofon. TAS was found lower (p<0.001), and OSI was higher in both breeds (Montofon p=0.012, Simmental p=0.028) after calving than in pregnancy. When compared between pregnancy and after calving levels in the same breed, HDL was found to be higher after calving (p<0.001) and TG was lower after calving (p=0.020) in Montofon. PON (p=0.090), HDL (p<0.001) and cholesterol levels were found higher (p<0.001) and TG level was lower (p<0.001) after calving in Simmental. According to our results, we observed different responses between two breeds before and after calving. There are few studies about TDH in animal research, and this is the first study in the literature that evaluates the TDH along with oxidative stress and lipid profiles in dairy cows in the periparturient and post-partum period.

Assessing antioxidant responses in C6 and U-87 MG cell lines exposed to high copper levels

Copper excess has been tested as an anticancer therapy, due to its properties to generate oxidative stress resulting in tumoral cell death. Thus, this study aimed to evaluate the impact of copper excess on oxidative stress and antioxidant responses in glioma cells, establishing the antioxidant system as a target of copper toxicity in tumoral cells. C6 and U-87 MG cells were exposed to CuSO4 (0–600 μM) for 24-48 h. SOD, CAT, GPx, GR, and CK activities, protein and non-protein thiol levels (PSH and NPSH), and O2− production were assessed, alongside SOD1, GPx1, and GR gene expression. Results revealed a decrease in GPx, GR, and CAT activity after CuSO4 exposure in both cell lines over 24-48 h, while SOD activity initially increased, then declined after 48 h. CK activity was also decreased in C6 cells. NPSH and PSH levels dropped after 24 h, and O2− production was observed in all CuSO4 concentrations. GR mRNA was reduced in both cell lines, contrasting with increased GPx1 mRNA in C6. U-87 MG cells exhibited higher levels of SOD1 mRNA, while C6 cells displayed lower expression. Our findings suggest that copper excess limits antioxidant enzyme activity and thiol levels, particularly in the C6 cells, likely attributable to oxidative stress or direct copper-enzyme interactions. Moreover, our results imply differences in copper toxicity regarding the cell lineage used, highlighting the importance of analyzing high copper levels effects in different models. Moreover, it could be proposed that the antioxidant system is a target of copper toxicity, contributing to glioma cell death.

Copper sulfate-induced stress in Spinach: Metabolic pathway disruption and plant response

Copper sulfate (CuSO4) stress profoundly affects plant growth by interfering with key metabolic pathways. This disruption leads to significant alterations in various physiological parameters, ultimately impacting the overall health and productivity of the plant. This study assessed the impact of CuSO4 stress on spinach (Spinacia oleracea L.) through a pot experiment using CuSO4 concentrations of 0, 75, 125, and 175 ppm. We noticed that at 75 ppm, CuSO4 improved plant height and the concentration of soluble sugar and ascorbic acid compared to the control. Additionally, amino acid, phenol, proline, fresh weight, and moisture content peaked at 175 ppm. Conversely, at 125 and 175 ppm, plant height, dry weight, leaf area, and concentrations of ascorbic acid and sugar significantly decreased. Moreover, at 175 ppm, there were substantial decreases in chlorophyll a (14.8%), chlorophyll b (73.6%), carotenoids (15%), and photosynthetic rates compared to the control. However, the chlorophyll a to chlorophyll b ratio increased by 29.53% at 175 ppm. In addition, protein and phenol contents diminished at 75 and 125 ppm. Elevated CuSO4 levels increased non-protein thiol levels while reducing the activities of superoxide dismutase, catalase, ascorbate peroxidase, and glutathione peroxidase. Stress hormones such as abscisic acid, jasmonic acid, and ethylene increased with CuSO4 stress, whereas growth hormones indol-acetic acid and gibberellic acid declined. This study demonstrates that spinach shows improved growth and metabolic function at 75 ppm CuSO4, indicating tolerance to mild stress. However, higher CuSO4 concentrations (125 and 175 ppm) significantly reduce growth parameters, chlorophyll content, and enzyme activities, highlighting the need for careful CuSO4 management in agriculture to avoid adverse effects on plant health and productivity.

Evaluation of Thiol Disulfide, Ischemia Modified Albumin, and Prolidase Parameters in Patients With Localized Scleroderma

Introduction: Localized scleroderma is a rare inflammatory skin disease that causes sclerosis in the dermis and subcutaneous tissue. Oxidative stress may play a role in the etiology or be responsible for the chronicity or progression of the disease. Objectives: We aimed to investigate the presence of oxidative stress in patients with localized scleroderma by examining thiol disulfide balance, ischemia-modified albumin (IMA), and prolidase parameters. Methods: Twenty patients over the age of 18, who were diagnosed with localized scleroderma both clinically and histopathologically and 20 control subjects were included in the study. Age, gender, age of disease onset, duration of the disease, and presence of accompanying systemic diseases were questioned and recorded. Lesion type and modified Rodnan and Lossi scores were calculated through dermatological examination. CRP, sedimentation rate, total thiol, native thiol, and disulfide levels indicated by the Erel profile, IMA level, and prolidase levels were measured and compared in both the patient and control groups. Results: Levels of native thiol (p=0.958), total thiol (p=0.979), disulfide (p=0.449), (disulfide/native thiol%) (p=0.368), (disulfide/total thiol%) (p=0.361), (native thiol/total thiol%) (p=0.368), and prolidase (p=0.121) were similar in both patient and control groups. Only IMA was significantly different. No significant relationship was found between the levels of native thiol, total thiol, disulfide, (disulfide/native thiol), (disulfide/total thiol), IMA, prolidase, and Rodnan and Lossi scores. Conclusion: According to the data obtained from this study, we can say that the thiol-disulfide balance is not disrupted and prolidase levels are not affected in localized scleroderma; however, IMA is negatively affected.

Development of a Novel Label-Free Subunit HILIC-MS Method for Domain-Specific Free Thiol Identification and Quantitation in Therapeutic Monoclonal Antibodies.

Cysteine residues are crucial for the formation of conserved disulfide bonds in therapeutic monoclonal antibodies (mAbs), which are essential for their folding and structural stability. The presence of free thiols in mAbs can indicate incomplete disulfide bond formation, potentially impacting the molecule's conformational stability. Free thiol quantitation has been achieved using labeling-based strategies such as maleimide and haloalkyl derivatives at both intact and peptide levels. However, intact-level measurement only provides total free thiol levels, while peptide-level measurement is time-consuming and more prone to assay-induced artifacts. In this study, we present a novel label-free HILIC-MS method that separates free thiol species at the subunit level, followed by free thiol localization by the MS2 fragmentation pattern. This allows for facile identification and quantitation of intrachain free thiols at domain-specific resolution. Compared to bottom-up approaches, this subunit HILIC-MS method excels in simpler sample preparation and higher throughput and enables chain-specific free thiol analysis for bispecific mAbs. This method can be readily applied for screening mAb candidates with elevated levels of free thiols in early-stage developability assessment and facilitating an effective comparability evaluation of mAb samples during process development.

PTZ KINDLING MODEL: EVALUATION OF EEG FACTOR AND BIOCHEMISTRY PARAMETERS UNDER THE INFLUENCE OF RAMELTEON

Many selective synthetic melatonin receptor agonists have anticonvulsant/anti-epileptogenic properties. These agonists bind to melatonin receptor 1 (MT1) and receptor 2 (MT2), causing their activation. Therefore, we evaluated the anticonvulsant effect of Ramelteon (RMLT) as a melatonin agonist in the PTZ (Pentylenetetrazol)-kindling model. In the study, 36 male Wistar Albino rats were assessed in 6 groups (Sham, PTZ, dimethylsulphoxide (DMSO), Valproic acid (VPA) (150 mg/kg) + PTZ, RMLT (30 mg/kg)+PTZ, VPA+RMLT+PTZ). Cortical electroencephalography (EEG) data were recorded for all groups. Seizures were scored according to the Racine scale. Seizure scores and onset times of the first myoclonic movements were compared in EEG traces. Total antioxidant status (TAS), total oxidant status (TOS), catalase, myeloperoxidase (MPO), and Thiol levels were measured in serum samples. Also, Calcineurin (CaN), Neuropeptide-Y (NPY), Neuron Specific Enolase (NSE), and S100B levels were measured in brain tissue samples. There was a significant difference between the PTZ and PTZ+Valproic acid+RMLT groups for the onset of the first myoclonic movements and the rate of spikes in the EEG traces in Racine's convulsion stages (P 0.05). RMLT has anticonvulsant properties. Additionally, the receptor preference of RMLT can be investigated.

Anti-inflammatory and antioxidative effects of essential oil of Hyptis crenata on the intestinal injuries induced by methotrexate

Methotrexate (MTX) is an important drug for the treatment of cancer and other diseases. However, it induces many gastrointestinal inflammation-related side effects. The essential oil of Hyptis crenata (EOHc) has gastrointestinal protective and anti-inflammatory properties. Therefore, we aimed to investigate the effect of EOHc on MTX-induced intestinal inflammation in rats. Male Wistar rats were administered MTX or Saline for 3 days and EOHc (300 mg/kg) or vehicle for an additional 3 or 7 days. Half of the animal was euthanized 3 days after the end of MTX treatment (inflammation phase) and the remaining half euthanized 4 days later (post-inflammation phase). The MPO levels in the mucositis inflammation-related phase of the MTX-treated group were 284 % of the control in the duodenum (cont: 50,9 ± 9,97 U/mg of protein) and 231 % of the control in the ileum (cont: 30,4 ± 6,60 U/mg of protein). In the EOHc group, the levels were 50 % of control in the duodenum and 113 % in the ileum. During this phase, EOHc prevented the increase in TBARs levels and the decrease in thiol levels in the duodenum and jejunum. In the post-inflammation phase of mucositis, EOHc prevented the gastrointestinal transit alteration and, in general, increased food and water consumption. In conclusion, the observed effects, particularly the anti-inflammatory and antioxidant effects of EOHc, as well as its previously reported low toxicity, position EOHc as a promising candidate for reducing gastrointestinal side effects associated with the use of MTX.

D-galactose Induces Senescence in Adult Mouse Neural Stem Cells by Imbalanced Oxidant and Antioxidant Activity and Differential Expression of Specific Hub Genes.

Cellular senescence is a permanent state of cell cycle arrest that occurs in proliferating cells under various stresses causing age-related disorders. This study investigated the role of D-galactose in inducing premature senescence of neural stem cells (NSCs) and the genes involved in this process. After NSC isolation and proliferation, senescence was induced with 10, 20, or 30µM concentrations of D-galactose for 24h. Cell viability was tested using the MTT assay, and senescent cells were identified based on increased lysosomal β-galactosidase activity. In addition, levels of NO and malondialdehyde (MDA) oxidative biomarkers but also total thiols (T-SH) and total antioxidant FRAP, as well as inflammatory cytokines, were investigated. Besides, RNA-Seq was performed on the various groups, the gene network was mapped, and genes with the most significant changes were examined. Treatment of NSCs with 20 or 30µM concentrations of D-galactose caused a significant decrease in cell survival, a number of neurospheres, and a number of neurosphere-derived cells, compared to the control group. In addition, the number of BrdU + cells significantly decreased after induction of NSC senescence with 10 or 20μM D-galactose, whereas aging-related β-galactosidase (SA-β-gal) increased significantly. Moreover, treatment with 10 or 20μM D-galactose showed a significant increase in NO production, but not malondialdehyde (MDA). However, the levels of total thiol (T-SH) and antioxidant FRAP levels decreased significantly. Furthermore, TNF-α and IL-6 cytokines significantly increased in NSCs treated with 20μM, but not 10μM, D-galactose. Finally, a gene network consisting of 860 gene orthologs was mapped using RNA-Seq. Protein interactions were obtained in 11 hub genes which were classified using gene ontology based on molecular function, biological processes, or cellular processes. Genes with the most significant changes in aging included Fn1, Itga2, Itga3, Itga6, Itga8, Ptk2b, Grin2b, Cacna2d3, Pde4d, Shisa6, and Stac3. This study showed that D-galactose reduces NSC proliferation and antioxidant activity while increasing oxidative stress and inflammatory cytokines. A survey of the genes involved in premature aging may be used as therapeutic candidates for aging-related disorders.

Protective effect of essential oil of Foeniculum vulgare Mill. against bleomycin-induced pulmonary fibrosis and oxidative stress in rat

BackgroundWild fennel (Foeniculum vulgare Mill.) is a very common plant used in traditional medicine to treat several diseases. In recent years, scientific research proved its biological properties. However, the protective effect of fennel against bleomycin-induced pulmonary fibrosis (BLM-IPF) is not yet study. PurposeFennel essential oil (FEO) composition was characterized and its protective effect was assessed. MethodsGC–MS was employed to determine the chemical composition of fennel essential oil. The antioxidant activity was evaluated using TAC, DPPH, RAP and ABTS assays. After inducing fibrosis by bleomycin, several biological assays were used to evaluate the protective effect [proteins content, malondialdehyde MD, thiol group, superoxide dismutase (SOD) and catalase (CAT)]. ResultsFEO was rich in estragole (77.55 %), fenchone (9.23 %), and limonene (9.23 %), and phenolic compounds and showed a significant antioxidant potential. The effects on BLM-IPF were revealed by disruption and alteration of oxidative stress biomarkers in lung, liver and kidney. Treatment of rats with FEO improved abnormal fluctuations in protein and thiol levels, decreased oxidative stress in terms of MDA and also restored the response of the antioxidant system, measured in terms of SOD and CAT, in lung, liver and kidney. The biological activity was recorded in a dose response manner. The potential of FEO in limiting the progress of the histopathologic effects of BLM-IPF was confirmed by microscopic histological observations, with a reduction of the fibrosis score and the inflammatory index in the FEO treated lung tissue. ConclusionThese results, proved that FEO could attenuate BLM-induced PF, thus suggesting that the latter could serve as a potential therapeutic approach for PF.

Camel milk inhibits pulmonary oxidative stress and inflammation in a rat model of COPD induced by cigarette smoke exposure

BackgroundOne of the main causes of death in the world is chronic obstructive pulmonary disease (COPD) with partially reversible airflow limitation, which is defined as a preventable and treatable pathological condition. Anti-inflammatory and antioxidant properties of camel milk (CM) were indicated previously. The effect of CM in cigarette smoke induced-COPD in rats was evaluated in this study. MethodsFive groups of rats including a) control, b) chronic obstructive pulmonary diseases (COPD, cigarette smoke exposed), c) COPD group treated with dexamethasone, d) COPD group treated with low dose of camel milk (CM) and e) COPD group treated with high dose of CM by gavage during the cigarette smoke exposure period (n = 7) were studied. ResultsIn the COPD group, total and differential white blood cells (WBC) count in the bronchoalveolar fluid (BALF), tumor necrosis factor-alpha (TNF-α) level in the lung tissue and malondialdehyde (MDA) level in the BALF and lung tissue, lung pathological changes and tracheal responsiveness to methacholine were significantly increased, but catalase (CAT) and superoxide dismutase (SOD) activities and the level of thiol in the BALF and lung tissue were significantly decreased compared to the control group (all, p < 0.001). However, in the COPD groups treated with both doses of CM and dexamethasone, most variable did not achieved to the control levels and were significantly different with the control group (p < 0.05 to p < 0.001). In the COPD group treated with both doses of CM (dose dependently) and dexamethasone, almost all measured variables were significantly improved (p < 0.05 to p < 0.001). ConclusionThe potential effect of CM on lung inflammation and oxidative stress in a rat model of COPD comparable to dexamethasone was demonstrated.

Sodium transport and redox regulation in Saccharomyces cerevisiae under osmotic stress depending on oxygen availability

This study explores the molecular mechanisms behind the differential responses of Saccharomyces cerevisiae industrial strains (ATCC 9804 and ATCC 13007) to osmotic stress. We observed that, in contrast to ATCC 9804 strain, sodium flux in ATCC 13,007 is not N, N’-dicyclohexylcarbodiimide (DCCD)-sensitive under osmotic stress, suggesting a distinct ion homeostasis mechanism. Under aerobic conditions, osmotic stress increased reduced SH groups by 45% in ATCC 9804 and 34% in ATCC 13,007. In contrast, under microaerophilic conditions, both strains experienced a 50% reduction in thiol groups. Notably, ATCC 13,007 exhibited a 1.5-fold increase in catalase (CAT) activity under aerobic stress compared to standard conditions, while ATCC 9804 showed enhanced CAT activity due to SH group binding. Additionally, superoxide dismutase (SOD) activity was doubled during aerobic growth in both strains, with ATCC 13,007 showing a 1.5-fold higher SOD activity under osmotic stress. The results demonstrate that S. cerevisiae adapts to osmotic stress differently under aerobic and microaerophilic conditions, with aerobic conditions promoting Pma-Ena-Trk interplay, reduced thiol levels and increased catalase activity, while microaerophilic conditions demonstrate Pma-Nha-Trk interplay and shifts redox balance towards oxidized thiol groups and enhance superoxide dismutase activity. Understanding these mechanisms can aid in developing stress-resistant yeast strains for industrial applications.

Investigating the Hepatic Response to Orlistat and White Tea in Rats on a High-Fat Diet.

High-fat diets have detrimental health impacts that increase the likelihood of developing obesity and metabolic syndrome. This study aimed to examine the potential antioxidant and anti-inflammatory effects of orlistat and white tea in rats fed a high-fat diet. Thirty-two rats were randomized into four groups: control (standard diet), HFD (high-fat diet), HFD+Orlistat (high-fat diet+orlistat), and HFD+WT (high-fat diet+white tea extract). A significant increase in malondialdehyde (MDA) levels and a decrease in total thiol (TT) levels were detected in the HFD group (p < 0.001). On the other hand, a decrease in the MDA level (p < 0.001) and an increase in the TT level were observed in the orlistat and white tea groups compared with those in the HFD group (p < 0.001). Histopathological examinations revealed that, compared with the HFD alone, orlistat and white tea reduced fat accumulation, prevented degenerative changes in hepatocytes, and decreased the histopathological damage score (p = 0.001). Immunohistochemical examinations of nuclear factor-kappa B (NF-kB/p65) revealed that compared with the HFD, orlistat and white tea reduced immunopositivity (p = 0.001). White tea decreases lipid peroxidation and oxidative stress. Both white tea and orlistat decreased fat formation and inflammation in the liver and regulated inflammation by reducing Nf-kB positivity. Nevertheless, further research is needed to assess their impact on human subjects.

Protective Effects of Trimetazidine and Dexmedetomidine on Liver Injury in a Mesenteric Artery Ischemia-Reperfusion Rat Model via Endoplasmic Reticulum Stress.

Acute mesenteric ischemia can lead to severe liver damage due to ischemia-reperfusion (I/R) injury. This study investigated the protective effects of trimetazidine (TMZ) and dexmedetomidine (DEX) against liver damage induced by mesenteric artery I/R via endoplasmic reticulum stress (ERS) mechanisms. Twenty-four rats were divided into four groups: control, I/R, I/R+TMZ, and I/R+DEX. TMZ (20 mg/kg) was administered orally for seven days, and DEX (100 µg/kg) was given intraper-itoneally 30 min before I/R induction. Liver tissues were analyzed for creatinine, alanine ami-notransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBARS), and total thiol (TT) levels. Compared with the control group, the I/R group presented significantly increased AST, ALT, TBARS, and TT levels. TMZ notably reduced creatinine levels. I/R caused significant liver necrosis, inflammation, and congestion. TMZ and DEX treatments reduced this histopathological damage, with DEX resulting in a more significant reduction in infiltrative areas and vascular congestion. The increase in the expression of caspase-3, Bax, 8-OHdG, C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) decreased with the TMZ and DEX treatments. In addition, Bcl-2 positivity decreased both in the TMZ and DEX treatments. Both TMZ and DEX have protective effects against liver damage. These effects are likely mediated through the reduction in ERS and apoptosis, with DEX showing slightly superior protective effects compared with TMZ.

Chemical analysis of Alliin-Rich Allium sativum (Garlic) extract and its safety evaluation in Drosophila melanogaster

Garlic (Allium sativum) has been traditionally valued for its medicinal properties attributed to the presence of organosulfur compounds. Despite its benefits, concerns about herbal extract toxicity have arisen, necessitating safety assessment. This study was designed to evaluate the chemical analysis and safety profile of Alliin-Rich Garlic Extract (ARGE) using Drosophila melanogaster as a model organism. The ARGE was extracted from garlic cloves (Allium sativum Linn: UIH-23262) using a microwave-assisted method and characterized using UPLC-ESI-MS, 1H NMR, HPLC and IR. Its safety evaluation was determined using D. melanogaster (Harwich strain), and various assays were conducted on 1–3-day-old flies. Toxicological markers and oxidative stress were assessed to understand the impact of ARGE on the flies. Chemical profiling of ARGE using UPLC-ESI-MS, confirmed the presence of alliin (S-ally-L-cysteine-S-oxide), L-arginine, γ-glutamylmethionine, S-(2-carboxypropyl) glutathione, N-γ-glutamyl-S-(1-propenyl) cysteine, N-γ-glutamyl-S-(2-propenyl) cysteine, N-γ-glutamylphenylalanine, S-(allylthio) cysteine, γ-glutamyl-S-allylthiocysteine and eruboside B. HPLC confirmed an alliin content of 0.073 mg/g. Toxicological assessment in D. melanogaster revealed that ARGE enhanced antioxidant defenses by increasing total thiol levels and GST activity, while reducing acetylcholinesterase activity. No significant alteration was observed in catalase activity and cellular metabolic rate. Histological examination revealed no alterations in the histoarchitecture of the brain, fat body or gut of D. melanogaster. The study demonstrated the safety of ARGE in D. melanogaster, supporting its potential as a safe herbal remedy.

Determination of thiol-disulphide homeostasis in premenstrual syndrome during adolescence.

Premenstrual syndrome (PMS) characterized by cyclic symptoms during the luteal phase of the menstrual cycle, presents an uncertain etiology in adolescents involving hormonal fluctuations and serotonin-related neurotransmitters with a limited existing literature on the impact of oxidative stress. This study aimed to explore the potential association between PMS and oxidative stress in adolescents. In a cross-sectional study conducted at a university hospital, involving 45 adolescent girls aged 12 to 18, participants were categorized based on the presence or absence of PMS using the cut-off point of 110 on the PMS Scale developed by Gençdoğan. Oxidative stress was assessed through dynamic thiol-disulfide homeostasis. The shift from the balance towards disulfide form is associated with oxidative stress, whereas towards thiol it shows a greater antioxidant capacity. Thirty out of the forty-five participants were found to have PMS with a mean age of 15.5 years. The PMS group demonstrated a significant increase in antioxidant markers, specifically elevated native (631.6±57.55 vs 598.2±41.08, p=0.048) and total thiol levels (675.15±3.4 vs 639.3±44.9, p=0.031). Despite a significant increase in thiol, thiol to disulfide ratio was not found to be significant (p=0.849). Contradictory to other studies in adults, we have demonstrated an increase in the antioxidant markers in adolescents with PMS. Elevated antioxidant status in adolescents with PMS may be an adaptive response to acute cyclic inflammation in the adolescent period, which might decrease with the progression of age. Further research is needed to investigate the complex interaction between oxidative stress and PMS across different age groups.

Optimizing Oxalic Acid Application Regime to Maximize Sunflower Remediation Efficacy in Cd-Contaminated Soils

The exogenous application of oxalic acid is a potential approach to amplifying phytoremediation performance on Cd-contaminated soils. However, few studies explore the optimal oxalic acid application regime from a perspective of coupling different concentrations and timings to maximize Cd removal rate. Given this, a pot experiment was conducted using oil sunflower (Helianthus annuus L.) as the test plant. Oxalic acid was added to the pots at concentrations of 1, 2, 3, 4, 5, and 6 mmol/kg at 20, 30, 40, and 50 days after emergence. A control (CK) without exogenous oxalic acid was also included. We examined the discrepancies in various soil Cd forms, sunflower height, plant non-protein thiol (NPT) levels, and soil Cd remediation efficiency under different oxalic acid application regimes. The results showed that applying oxalic acid at a concentration of 4 mmol/kg reduced the proportion of Fe-Mn oxide Cd and organic Cd compared to the control (CK), while increased the proportion of available Cd. The optimal application time is 30 or 40 days after emergence. The addition of exogenous oxalic acid promoted the growth of sunflowers, with the greatest increase in plant height observed when 4 mmol/kg oxalic acid was applied at 30 days after emergence. Exogenous oxalic acid enhanced the absorption of Cd by sunflower roots, with the total Cd accumulation in roots, stems, and leaves being higher than in the control (CK). When 4 mmol/kg oxalic acid was applied at 30 days after emergence, the total Cd accumulation in roots, stems, and leaves was highest. Under different application times and concentration levels of oxalic acid, Cd accumulation was highest in roots, followed by leaves, with stems showing the lowest accumulation. The NPT content in each part is as follows: root &gt; stem &gt; leaf. Applying 5 mmol/kg oxalic acid after 30 days of sunflower emergence resulted in relatively higher total NPT content in roots, stems, and leaves compared to the control (CK). The TOPSIS model was used for comprehensive evaluation, which showed that 4 mmol/kg oxalic acid application at 30 days after emergence could be used as the optimal oxalic acid application regime for phytoremediation. These findings indicate that the addition of oxalic acid effectively promoted the absorption of Cd by sunflower and increased the efficiency of Cd removal from the rhizosphere soil, with the optimal removal of soil Cd achieved by applying oxalic acid at a concentration of 4 mmol/kg 30 days after the emergence of oilseed sunflower seedlings.

Isorhamnetin Alleviates Renal Fibrosis by Inducing Endogenous Hydrogen Sulfide and Regulating Thiol-Based Redox State in Obstructed Kidneys.

Isorhamnetin (ISO) is an active flavonoid compound mainly isolated from the fruits of Hippophae rhamnoides L. and the leaves of Ginkgo biloba L. Previous studies have revealed the antifibrotic action of ISO in the liver and lungs, although its potential protective effects against renal fibrosis and the underlying mechanisms are still poorly understood. Given that many actions of ISO could be similarly attained by hydrogen sulfide (H2S), we speculated that ISO may work through the induction of endogenous H2S. To test the hypothesis, we established the unilateral ureteral obstruction (UUO) renal fibrosis rat model and transforming growth factor-β1(TGF-β1)-induced fibrosis in cultured renal tubular cells. ISO treatment inhibited epithelial-mesenchymal transition (EMT) formation, decreased extracellular matrix (ECM) deposition, and relieved renal fibrosis. Further analysis revealed that ISO stimulated the expression of the H2S-synthesizing enzyme cystathionine lyase (CSE) and cystathionine beta-synthase (CBS), and promoted H2S production in vivo and in vitro. The elevated H2S attenuated oxidative stress and elevated the thiol level. It induced Keap1 sulfhydration, disrupted Keap1-Nrf2 interaction, and promoted the entry of Nrf2 into the nucleus. Finally, we found that circulating H2S mainly derived from the liver, and not the kidney. Collectively, our study revealed that ISO alleviated renal fibrosis by inducing endogenous H2S and regulating Keap1-Nrf2 interaction through sulfhydration of Keap1. Endogenous H2S could be an important mediator underlying the pharmacological actions of ISO. Due to the multifunctional properties of H2S, the H2S-inducing nature of ISO could be exploited to treat various diseases.