Thiol Levels Research Articles

Physical frailty is related to oxidative stress through thiol/disulfide homeostasis parameters.

To evaluate relationship between frailty and oxidative stress through thiol/disulfide homeostasis parameters [Native thiol (NT), total thiol (TT), and disulfide levels (D), disulfide-native thiol (D/NT), disulfide-total thiol (D/TT), native thiol-total thiol (NT/TT) ratios, and ischemia-modified albumin levels (IMA)]. In total, 139 community-dwelling older adults were included. The frailty status, defined by the FRIED frailty index (FFI) and Clinical Frailty Scale (CFS), and comprehensive geriatric assessment results compared with thiol/disulfide homeostasis parameters and ischemia-modified albumin levels. NT and TT levels were significantly lower in the frail group (respectively; p = 0.014, p = 0.020). The FFI scores were correlated with the levels of NT, TT, D/NT, D/TT, and NT/TT (respectively; r = - 0.25, r = - 0.24, r = 0.17, r = 0.17, r = - 0.17). The significant correlation could not be retained with the CFS scores. In ROC analysis, the AUC for NT was calculated as 0.639 in diagnosing frailty according to the FFI (95% CI 0.542-0.737), AUC was 0.638 for TT (95% CI 0.540-0.735), and AUC was 0.610 for NT/TT (95% CI 0.511-0.780). The AUC was calculated as 0.610 for both D/NT and D/TT in diagnosing physical frailty (95% CI 0.511-0.708). Thiol/disulfide homeostasis parameters can be a potential biomarker in diagnosing physical frailty. However, further studies are needed for diagnosing frailty defined with cumulative deficit models.

Assessing physiological responses and oxidative stress effects in Rhamdia voulezi exposed to high temperatures.

Exposure to high temperatures induces changes in fish respiration, resulting in an increased production of reactive oxygen species. This, in turn, affects the enzymatic and non-enzymatic components of antioxidant defenses, which are essential for mitigating cellular stress. Rhamdia voulezi, an economically important fish species endemic to Brazil's Iguaçu River, served as the subject of our study. Our goal was to assess enzymatic antioxidant biomarkers (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, glucose-6-phosphate dehydrogenase), non-protein thiol levels (reduced glutathione), and markers of oxidative damage (lipoperoxidation and carbonylation) in the liver, gills, and kidneys of R. voulezi after acute exposure to high temperatures (31°C) for 2, 6, 12, 24, and 96 h. Control groups were maintained at 21°C. Our findings revealed that the liver exhibited increased superoxide dismutase levels up to 12 h and elevated glutathione S-transferase levels at 12 and 96 h at 31°C. In the gills, superoxide dismutase levels increased up to 24 h, along with increased lipoperoxidation at 2, 6, 12, and 96 h of exposure to high temperatures. The kidneys responded to heat stress at 12 h, with an increase in superoxide dismutase and catalase activity, and lipid peroxidation was observed at 2 and 6 h at 31°C. The three tissues evaluated responded differently to heat stress, with the liver demonstrating greater physiological adjustment to high temperatures. The intricate interplay of various antioxidant defense biomarkers and oxidative damage suggests the presence of oxidative stress in R. voulezi when exposed to high temperatures.

Systemic and Lung Inflammation and Oxidative Stress Associated With Behavioral Changes Induced by Inhaled Paraquat Are Ameliorated by Carvacrol.

Paraquat (PQ) is an herbicide toxin that induces injury in different organs. The anti-inflammatory and antioxidant effects of carvacrol were reported previously. The effects of carvacrol and pioglitazone (Pio) alone and their combination on inhaled PQ-induced systemic and lung oxidative stress and inflammation as well as behavioral changes were examined in rats. In this study, animals were exposed to saline (control [Ctrl]) or PQ (PQ groups) aerosols. PQ-exposed animals were treated with 0.03 mg/kg/day dexamethasone (Dexa), 20 and 80 mg/kg/day carvacrol (C-L and C-H), 5 mg/kg/day Pio, and Pio+C-L for 16 days. Inhaled PQ markedly enhanced total and differential white blood cell (WBC) counts, nitric oxide (NO), and malondialdehyde (MDA) levels but decreased catalase (CAT) and superoxide dismutase (SOD) activities and thiol levels both in the bronchoalveolar lavage fluid (BALF) and blood and increased interferon-gamma (INF-γ) and interleukin-10 (IL-10) levels in the BALF (p < 0.001 for all cases) except lymphocyte count in blood which was not significantly changed. The escape latency and traveled distance were increased in the PQ group. However, the time spent in the target quadrant in the Morris water maze (MWM) test and the duration of time latency in the dark room in the shuttle box test were reduced after receiving an electrical shock (p < 0.05-p < 0.001). Inhaled PQ-induced changes were significantly improved in carvacrol, Pio, Dexa, and especially in the combination of the Pio+C-L treated groups (p < 0.05-p < 0.001). Carvacrol and Pio improved PQ-induced changes similar to Dexa, but ameliorative effects produced by combination treatments of Pio+C-L were more prominent than Pio and C-L alone, suggesting a potentiating effect for the combination of the two agents.

Evaluation of the protective effect of coenzyme Q10 on hepatotoxicity caused by acute phosphine poisoning.

Background: Aluminum phosphide (AlP) poisoning is prevalent in numerous countries, resulting in high mortality rates. Phosphine gas, the primary agent responsible for AlP poisoning, exerts detrimental effects on various organs, notably the heart, liver and kidneys. Numerous studies have documented the advantageous impact of Coenzyme Q10 (CoQ10) in mitigating hepatic injuries. The objective of this investigation is to explore the potential protective efficacy of CoQ10 against hepatic toxicity arising from AlP poisoning. Method: The study encompassed distinct groups receiving almond oil, normal saline, exclusive CoQ10 (at a dosage of 100mg/kg), AlP at 12mg/kg; LD50 (lethal dose for 50%), and four groups subjected to AlP along with CoQ10 administration (post-AlP gavage). CoQ10 was administered at 10, 50, and 100mg/kg doses via Intraparietal (ip) injections. After 24h, liver tissue specimens were scrutinized for mitochondrial complex activities, oxidative stress parameters, and apoptosis as well as biomarkers such as aspartate transaminase (AST) and alanine transaminase (ALT). Results: AlP induced a significant decrease in the activity of mitochondrial complexes I and IV, as well as a reduction in catalase activity, Ferric Reducing Antioxidant Power (FRAP), and Thiol levels. Additionally, AlP significantly elevated oxidative stress levels, indicated by elevated reactive oxygen species (ROS) production, and resulted in the increment of hepatic biomarkers such as AST and ALT. Administration of CoQ10 led to a substantial improvement in the aforementioned biochemical markers. Furthermore, phosphine exposure resulted in a significant reduction in viable hepatocytes and an increase in apoptosis. Co-treatment with CoQ10 exhibited a dose-dependent reversal of these observed alterations. Conclusion: CoQ10 preserved mitochondrial function, consequently mitigating oxidative damage. This preventive action impeded the progression of heart cells toward apoptosis.

Biotin-functionalized nanoparticles: an overview of recent trends in cancer detection.

Electrochemical bio-sensing is a potent and efficient method for converting various biological recognition events into voltage, current, and impedance electrical signals. Biochemical sensors are now a common part of medical applications, such as detecting blood glucose levels, detecting food pathogens, and detecting specific cancers. As an exciting feature, bio-affinity couples, such as proteins with aptamers, ligands, paired nucleotides, and antibodies with antigens, are commonly used as bio-sensitive elements in electrochemical biosensors. Biotin-avidin interactions have been utilized for various purposes in recent years, such as targeting drugs, diagnosing clinically, labeling immunologically, biotechnology, biomedical engineering, and separating or purifying biomolecular compounds. The interaction between biotin and avidin is widely regarded as one of the most robust and reliable noncovalent interactions due to its high bi-affinity and ability to remain selective and accurate under various reaction conditions and bio-molecular attachments. More recently, there have been numerous attempts to develop electrochemical sensors to sense circulating cancer cells and the measurement of intracellular levels of protein thiols, formaldehyde, vitamin-targeted polymers, huwentoxin-I, anti-human antibodies, and a variety of tumor markers (including alpha-fetoprotein, epidermal growth factor receptor, prostate-specific Ag, carcinoembryonic Ag, cancer antigen 125, cancer antigen 15-3, etc.). Still, the non-specific binding of biotin to endogenous biotin-binding proteins present in biological samples can result in false-positive signals and hinder the accurate detection of cancer biomarkers. This review summarizes various categories of biotin-functional nanoparticles designed to detect such biomarkers and highlights some challenges in using them as diagnostic tools.

Avaliação do potencial gastroreparador da bebida funcional fermentada de laranja contra úlcera gástrica induzida por etanol em ratos

ABSTRACT: Previous investigations have revealed that a functional fermented orange beverage presented in its composition different phenolic compounds, which through in silico investigation demonstrated to have biological effects of therapeutic importance as antioxidant, gastrorepair, and anti-ulcerative properties. Thus, this study confirmed in vivo, through a model of EtOH-induced gastric ulcers in rats, the beneficial properties indicated by the in silico tests. Gastric ulcer was induced by EtOH (intragastric) and was treated after 1 h with fermented orange beverage with and without Menthapiperita extract (0.5 mL/100 g w.b). Omeprazole was used as positive control. Histopathological evaluation revealed that EtOH administration resulted in the formation of gastric ulcers due to the reduction of the mucus layer, presence of hemorrhage, and infiltration of neutrophils in the stomach tissue of rats, and only treatment with omeprazole was able to reverse these changes. Additionally, EtOH administration altered the gastric juice volume and induced oxidative stress in the gastric tissue observed through the increase in lipid peroxidation (TBARS), reduction in the levels of non-protein thiols (NPSH), and alteration in the superoxide dismutase (SOD) activity. The ingestion of the fermented orange beverage increased NPSH levels and reduced changes in TBARS levels induced by ethanol. These findings suggested that the fermented orange beverage has antioxidant effects, as pointed out by in silico studies, but not gastrorepair and anti-ulcerative effects.

Ora-pro-nobis (Pereskia aculeata) supplementation promotes increased longevity associated with improved antioxidant status in Drosophila melanogaster.

This study evaluated the effects of ora-pro-nobis (Pereskia aculeate) flour supplementation on the in vivo basal antioxidant system of Drosophila melanogaster, and its action on the neural modulation observed by the enzyme acetylcholinesterase (AChE). The flies will receive a standard diet with flour incorporated at 5, 10 and 20% for 7 days. There was no change in food consumption, body weight, protein thiol levels and negative geotaxis behavior. The flies showed a reduction in the basal production of reactive species at concentrations of 10 and 20%, while there was a reduction in lipid peroxidation and catalase activity at all concentrations, accompanied by an increase in the levels of non-protein thiols. Superoxide dismutase activity was reduced in the 5 and 20% groups, while the reduction of superoxide anion in the 10% group may have contributed to the increase in longevity also in the 10% group. Longevity increased in groups 5 and 10%. The open field test may be related to the reduction in AChE activity in the 5, 10 and 20% groups. In general, the data show that supplementation with ora-pro-nobis flour at the concentrations tested did not cause toxicity and modulated the cholinergic system, demonstrating a therapeutic potential.

Use of Lactoferrin Supplement as an Efficient Antioxidant to Ameliorate the Effects of Mercury-induced Oxidative Stress in Male Wistar Rats

Background: The present study was carried out to test the antioxidant activity of lactoferrin as a dietary supplement to alleviate the effects of oxidative stress induced by mercury toxicity. Hematological and biochemical assays were employed to evaluate the ameliorating effects of lactoferrin. Methods: Sixty male Wistar rats were allotted randomly and equally into three groups; animals in Group 1 served as untreated control, animals in Group 2 were administered orally with mercuric chloride (HgCl2) at the dose of 6 mg/kg bw/day, and animals in Group 3 were administered with HgCl2 at the same dose and orally dosed with lactoferrin (400 mg/kg bw/day). Hematological indices (erythrocytic and total leukocytic counts, hemoglobin concentration%, and packed cell volume, (PCV%), and biochemical parameters (serum and homogenates of liver and kidney tissues) were assessed in all animals. Serum and tissue homogenate levels of total thiols, glutathione (GSH), catalase, and total antioxidant capacity (TAC) represented the antioxidant markers. The oxidation markers were represented by H2O2 and malondialdehyde (MDA). Results: Compared to the untreated control group, animals in Group 2 (administered with HgCl2) exhibited significantly increased levels of serum enzymes (alanine transferase (ALT), aspertate transferase (AST), and alkaline phosphatase), urea, blood urea nitrogen, creatinine, H2O2, and MDA. These animals showed significantly decreased levels of erythrocytic and total leukocytic counts, hemoglobin concentration, PCV%, total proteins, total thiols, GSH, catalase, and TAC. The hematological and biochemical changes were comparatively reversed toward the control levels in animals of Group 3 (administered with HgCl2 and orally dosed with lactoferrin). The reversed levels of hematological and biochemical parameters were significantly different compared to Group 2. Conclusions: Based on the encountered amelioration of the assayed hematological and biochemical parameters in animals treated with HgCl2 and given lactoferrin, it could be concluded that lactoferrin as a dietary supplement might function as an efficient antioxidant to alleviate the oxidative stress induced by mercury toxicity.

Comparison of preoperative and postoperative serum thiol/disulfide levels in patients undergoing laparoscopic sleeve gastrectomy for morbid obesity.

Obesity, a prevalent chronic disease, results from an imbalance between energy intake and expenditure. The oxidative stress associated with obesity stems from an imbalance between reactive oxygen species and the cell's antioxidant defense system. Oxidative stress can cause many diseases. The assessment of thiol/disulfide balance, a biochemical test, can be used to detect oxidative stress. The aim of this study is to determine the changes in oxidative stress associated with obesity after obesity surgery by assessing the thiol/disulfide levels. The study was conducted with 40 volunteer patients with a body mass index (BMI) above 40 who underwent obesity surgery at Harran University Hospital General Surgery. Thiol and disulfide levels and other blood parameters were measured from the preoperative and postoperative 2nd and 6th-month blood samples of the patients. BMI was calculated by recording the weights and heights of the cases. Patients with diseases that could affect oxidative stress measurements and those using medication were excluded from the study, and the analyses were performed accordingly. The results showed a statistically significant decrease in native thiol, disulfide, reduced thiol, oxidized thiol, glucose, ALT (alanine aminotransferase), ALP (alkaline phosphatase), total cholesterol, HDL (high-density lipoprotein), triglyceride, and BMI values between the preoperative, 2-month postoperative, and 6-month postoperative measurements (p<0.05). Restrictive methods such as sleeve gastrectomy in individuals with morbid obesity led to weight control and a decrease in adipose tissue, reducing oxidative stress and increasing antioxidant response.

Evaluations of Oxidative Stress, Thiol/Disulphide Homeostasis, and Nitric Oxide in Patients with Aneurysmal Subarachnoid Hemorrhage.

To investigate changes in nitric oxide (NO) levels, oxidative stress, and dynamic thiol/disulphide homeostasis in the serum and cerebrospinal fluid (CSF) of patients with aneurysmal subarachnoid hemorrhages (aSAH). This prospective study included a total of 40 consecutive patients suffering from aSAH, who were operated on within the first 48 hours from onset of symptoms; CSF and blood samples were collected from these patients during their operations. To create a control group, blood samples and cerebrospinal fluid were taken from patients (n=40) without neurologic disorders who had undergone lumbar puncture for spinal anesthesia. We observed that the serum total antioxidant status had decreased markedly (p=0.0143) but that no change was evident in the oxidative stress index and total oxidant status in aSAH patients when compared to the controls. While total thiol (p=0.0014) and native thiol (p < 0.0001) levels had decreased in the aSAH patients, disulphide levels (p < 0.0001) had increased significantly. Although the native thiol/total thiol ratio declined (p < 0.0001), the dynamic disulphide/total thiol ratio (p < 0.0001) and dynamic disulphide/native thiol ratio (p < 0.0001) increased markedly in serum samples from the patient group. Patient serum NO levels were also significantly elevated (p < 0.0001). There were no marked changes in CSF for all measured parameters (p > 0.05). This study demonstrated that serum NO levels and oxidative stress parameters increased markedly in the patients. These results may help to understand the underlying mechanisms behind early tissue damage due to aSAH and to monitor disease progression and improve the early detection of disease severity.

Did diet compliance and remission reduce oxidative stress in celiac patients?

We aimed to examine the effect of remission status on thiol-disulfide homeostasis in celiac patients and thus to indirectly determine the effect of oxidative stress and inflammation caused by non-compliance with the diet. Between February 2019 and December 2021, 117 patients diagnosed with celiac disease were included in this prospective randomized and controlled study. In addition to routine tests of celiac patients, thiol and disulfide measurements were made from the blood both at the beginning of the study and at the end of the first year. While 52 of the patients (44.4%) were in remission, 65 patients (55.6%) were not. There was an evident increase in native thiol levels of the patients who were initially not in remission but went into at the end of the first year (347.4±46.7 μmol/L vs. 365.3±44.0 μmol/L; p=0.001). Mean plasma disulfide levels of patients with celiac going into remission became reduced in the first year from the level of 14.5±5.1 μmol/L down to 8.9±4.2 μmol/L (p<0.001). In celiac patients who entered remission, disulfide and anti-tissue transglutaminase immunoglobulin A levels decreased in a correlation (r=0.526; p<0.001). Not being in remission in celiac disease leads to increased oxidative stress, and thiol-disulfide homeostasis is an indirect indicator of this. Additionally, providing remission in celiac patients reduces oxidative stress.

Dynamic thiol/disulfide homeostasis and myeloperoxidase levels in Gilbert's syndrome with mild hyperbilirubinemia.

This study aimed to compare dynamic thiol/disulfide homeostasis and myeloperoxidase (MPO) levels in patients with Gilbert's syndrome (GS) and healthy controls. Thiol/disulfide homeostasis and MPO levels are both associated with increased progression of atherosclerosis. The study included a total of 130 voluntary participants comprising 65 patients with GS and 65 healthy controls. These patients were selected randomly and dynamic thiol/disulfide homeostasis, MPO, complete blood count results, and biochemistry and lipid parameters were evaluated. Patients with known chronic diseases, medication usage, and acute infections were excluded from the study. Serum total thiol and native thiol levels were measured using the fully automated colorimetric method, while serum MPO levels were measured using the sandwich ELISA method. We found that patients with GS had significantly higher total thiol (352.3±38.6 vs. 317.9±47.9, p<0.001) and native thiol (386.6±42.6 vs. 348.0±51.1, p<0.001) and significantly lower disulfide (15.7±4.0 vs. 17.3±4.0, p=0.022) and MPO (130.7 vs. 166.3, p=0.006). In patients with bilirubin of <1 mg/dL, total thiol and native thiol levels were lower and disulfide, disulfide/native thiol (DNT) and disulfide/total thiol (DTT) ratios, and MPO levels were higher. Patients with bilirubin of <1 mg/dL also had higher total cholesterol. In these patients with GS, the thiol/disulfide balance shifted towards thiols and proinflammatory MPO levels were lower. When bilirubin was <1 mg/dL, disulfide, DNT and DTT ratios, and MPO were higher. Bilirubin levels affected all parameters of thiol/disulfide homeostasis and MPO levels independently of other risk factors. In light of our results, we suggest that mild hyperbilirubinemia in cases of GS has an anti-inflammatory and antioxidant effect and may be protective against atherosclerosis.

Effects of Supplementation of Murici (Byrsonima crassifolia) and Taperebá (Spondias mombin) Pulp Extracts on Food Intake, Body Parameters, and Oxidative Stress Markers in Healthy Rats.

This study evaluates the effects of supplementation of murici (Byrsonima crassifolia) and taperebá (Spondias mombin) pulp extracts on dietary intake, body composition, biochemical parameters, and markers of oxidative stress. Two experiments were conducted with a total of 80 healthy male Wistar rats and a 30-day supplementation. In the first experiment, animals were divided into control (C) group, murici group 50 mg/(kg⸱day) (50Mu), murici group 100 mg/(kg⸱day) (100Mu), and murici group 200 mg/(kg⸱day) (200Mu). In the second experiment, animals were divided into C group, taperebá group 50 mg/(kg⸱day) (50Tap), taperebá group 100 mg/(kg⸱day) (100Tap), and taperebá group 200 mg/(kg⸱day) (200Tap). Results showed lower feed intake in 50Mu, 100Mu, and 100Tap groups (13%, 12%, and 10%, respectively, P < .05) and lower body fat in 200Mu, 100Tap, and 200Tap groups (16.0%, 29.1%, and 27.1%, respectively, P < .05). Only the 100Tap group showed reduced adipose tissue content (30.4%; P < .05). Increased plasma antioxidant capacity was observed at all doses for both fruits. Taperebá supplementation reduced ferrous oxidation-xylenol orange levels (50Tap: 8.4%, 100Tap: 16.1%, 200Tap: 24.3%; P < .05) and increased thiol levels (50Tap: 39%, 100Tap: 31%; P < .05). Serum thiobarbituric acid reactive substances levels were reduced in all groups receiving taperebá (50Tap: 77.7%, 100Tap: 73.1%, 200Tap: 73.8%; P < .05) and murici (50Mu: 44.5%, 100Mu: 34%, 200Mu: 43%; P < .05). Therefore, it is suggested that the inclusion of these fruits in the diet can contribute to health maintenance and disease prevention, through their effects on controlling food intake, improving body composition, and in combating oxidative stress.

Increased production of inflammatory cytokines by circulating monocytes in mesial temporal lobe epilepsy: A possible role in drug resistance

We analyzed peripheral blood mononuclear cells (PBMCs) and serum inflammatory biomarkers in patients with mesial temporal lobe epilepsy (drug-resistant – DR, vs. drug-sensitive – DS). Patients with epilepsy showed higher levels of serum CCL2, CCL3, IL-8 and AOPP, and lower levels of FRAP and thiols compared to healthy controls (HC). Although none of the serum biomarkers distinguished DR from DS patients, when analysing intracellular cytokines after in vitro stimulation, DR patients presented higher percentages of IL-1β and IL-6 positive monocytes compared to DS patients and HC. Circulating innate immune cells might be implicated in DR epilepsy and constitute potential new targets for treatments.

Perampanel increases seizure threshold in pentylenetetrazole-kindled mice and improves behavioral dysfunctions by modifying mRNA expression levels of BDNF/TrkB and inflammatory markers

Perampanel (PER), a novel 3rd-generation antiseizure drug that modulates altered post-synaptic glutamatergic storming by selectively inhibiting AMPA receptors, is recently approved to treat intractable forms of seizures. However, to date, presumably consequences of long-term PER therapy on the comorbid deleterious psychiatric disturbances and its correlation with neuroinflammatory parameters are not fully investigated in chronic models of epilepsy. Therefore, we investigated the real-time effect of PER on brain electroencephalographic (EEG) activity, behavioral alterations, redox balance, and relative mRNA expression in pentylenetetrazole (PTZ) induced kindling. Male BALB/c mice were pretreated with PER (0.125, 0.25, and 0.5 mg/kg) for 3 weeks and challenged with 11 injections of PTZ at the sub-threshold dose of 40 mg/kg every other day. vEEG from implanted cortical electrodes was monitored to elucidate seizure propagation and behavioral manifestations. Recorded EEG signals exhibited that PER 0.5 mg/kg pretreatment exceptionally impeded the onset of sharp epileptic spike-wave discharges and associated motor symptoms. Additionally, qEEG analysis showed that PER prevented alterations in absolute mean spectral power and reduced RMS amplitude of epileptogenic spikes vs PTZ control. Furthermore, our outcomes illustrated that PER dose-dependently attenuated PTZ-evoked anxiety-like behavior, memory deficits, and depressive-like behavior that was validated by a series of behavioral experiments. Moreover PER, significantly reduced lipid peroxidation, AChE, and increased levels of SOD and total thiol in the mice brain via AMPAR antagonism. Post-PTZ kindling provoked overstimulation of BDNF/TrkB signaling and increased release of pro-inflammatory cytokines that were reversed by PER with suppression of iNOS in brain immune cells. In conclusion, our findings highlight that PER might play an auspicious preventive role in the proepileptic transformation of brain circuits via suppression of BDNF/TrkB signaling and reduced transcriptional levels of neuroinflammatory markers leading to improvised epilepsy-induced neurobehavioral and neurochemical effects.

The protective effects of betanin on titanium dioxide (TiO2) nanoparticle exposure in rats

The aim of this study was to investigate the protective properties of betanin in rats exposed to Titanium dioxide (TiO2) nanoparticles. An experimental animal study was conducted on 40 Spraque Dawley rats. The rats were studied in 4 groups (n = 10). Group I: Control group, Group II: TiO2 group (250 mg/kg/bw), Group III: TiO2 + Betanin group (250 mg/kg/bw TiO2 + Betanin; 100 µg/ml), Group IV: Betanin group (100 µg/ml). After 28 days of application, blood and liver tissue samples of the rats were collected. Total Antioxidant Status (TAS, mmol Trolox Eq/L), Total Oxidant Status (TOS, µmol H2O2 Eq/L), Paraoxonase (PON, U/L), Total thiol (μmol/L), Nitric oxide (NO, µmol/L), Malondialdehyde (MDA, nM/ml) and Catalase (CAT, U/mg protein) activity levels in the blood and liver tissue measured. Liver tissue samples were evaluated by immunohistochemical methods (Caspase-3 and 8-Hydroxy-2'-deoxyguanosine) and hematoxylin-eosin staining. As a result, a significant (p < 0.001) increase in the mean oxidant parameters and a significant (p < 0.001) decrease in the antioxidant parameters were determined in the TiO2 group when compared to the control group. Caspaze-3 and 8-OHdG histopathological results findings indicated a similar situation. However, it was determined that TiO2 damage was significantly reduced (p < 0.001) in rats to which TiO2 and betanin were administered together. In addition, the highest antioxidant levels and low histopathological damage were determined among all groups in the betanin-only group. Betanin (C24H26N2O13) shows protective activity in oxidative tissue damage caused by TiO2 nanoparticles.

Assessing the disparity: comparative toxicity of Copper in zebrafish larvae exposes alarming consequences of permissible concentrations in Brazil

ABSTRACT Copper (Cu) is a naturally occurring metal with essential micronutrient properties. However, this metal might also pose increased adverse environmental and health risks due to industrial and agricultural activities. In Brazil, the maximum allowable concentration of Cu in drinking water is 2 mg/L. Despite this standard, the impact of such concentrations on aquatic organisms remains unexplored. This study aimed to evaluate the toxicity of CuSO4 using larval zebrafish at environmentally relevant concentrations. Zebrafish (Danio rerio) larvae at 72 hr post-fertilization (hpf) were exposed to nominal CuSO4 concentrations ranging from 0.16 to 48 mg/L to determine the median lethal concentration (LC50), established at 8.4 mg/L. Subsequently, non-lethal concentrations of 0.16, 0.32, or 1.6 mg/L were selected for assessing CuSO4 -induced toxicity. Morphological parameters, including body length, yolk sac area, and swim bladder area, were adversely affected by CuSO4 exposure, particularly at 1.6 mg/L (3.31 mm ±0.1, 0.192 mm2 ±0.01, and 0.01 mm2 ±0.05, respectively). In contrast, the control group exhibited values of 3.62 mm ±0.09, 0.136 mm2 ±0.013, and 0.3 mm2 ±0.06, respectively. Behavioral assays demonstrated impairments in escape response and swimming capacity, accompanied by increased levels of reactive oxygen species (ROS) and lipid peroxidation. In addition, decreased levels of non-protein thiols and reduced cellular viability were noted. Data demonstrated that exposure to CuSO4 at similar concentrations as those permitted in Brazil for Cu adversely altered morphological, biochemical, and behavioral endpoints in zebrafish larvae. This study suggests that the permissible Cu concentrations in Brazil need to be reevaluated, given the potential enhanced adverse health risks of exposure to environmental metal contamination.

Acquired Radiation Resistance Induces Thiol-dependent Cisplatin Cross-resistance.

Resistance to radiation remains a significant clinical challenge in non-small cell lung carcinoma (NSCLC). It is therefore important to identify the underlying molecular and cellular features that drive acquired resistance. We generated genetically matched NSCLC cell lines to investigate characteristics of acquired resistance. Murine Lewis lung carcinoma (LLC) and human A549 cells acquired an approximate 1.5-2.5-fold increase in radiation resistance as compared to their parental match, which each had unique intrinsic radio-sensitivities. The radiation resistance (RR) was reflected in higher levels of DNA damage and repair marker γH2AX and reduced apoptosis induction after radiation. Morphologically, we found that radiation resistance A549 (A549-RR) cells exhibited a greater nucleus-to-cytosol (N/C) ratio as compared to its parental counterpart. Since the N/C ratio is linked to the differentiation state, we next investigated the epithelial-to-mesenchymal transition (EMT) phenotype and cellular plasticity. We found that A549 cells had a greater radiation-induced plasticity, as measured by E-cadherin, vimentin and double-positive (DP) modulation, as compared to LLC. Additionally, migration was suppressed in A549-RR cells, as compared to A549 cells. Subsequently, we confirmed invivo that the LLC-RR and A549-RR cells are also more resistance to radiation than their isogenic-matched counterpart. Moreover, we found that the acquired radiation resistance also induced resistance to cisplatin, but not carboplatin or oxaliplatin. This cross-resistance was attributed to induced elevation of thiol levels. Gamma-glutamylcysteine synthetase inhibitor buthionine sulfoximine (BSO) sensitized the resistant cells to cisplatin by decreasing the amount of thiols to levels prior to obtaining acquired radiation resistance. By generating radiation-resistance genetically matched NSCLC we were able to identify and overcome cisplatin cross-resistance. This is an important finding arguing for combinatorial treatment regimens including glutathione pathway disruptors in patients with the potential of improving clinical outcomes in the future.

Ameliorative and protective effect of Bergenia ciliata (Haw.) Sternb. extract against acetaminophen-induced hepato-renal damage in rats: B. ciliata and hepato-renal damage

Background: Bergenia ciliata (Haw.) Sternb. is a medicinal plant bestowed with antioxidative phytochemicals and has been traditionally associated with several medicinal and health-promoting properties and used in the management of diseases.Method: The study was undertaken to determine the potential of the extract of the rhizome of Bergenia ciliata (Haw.) Sternb. at 150 and 300 mg/kg body weight (BW) to attenuate the drug-induced oxidative damage in hepatic and renal tissues of Wistar rats. The toxicity was induced by a single oral administration of acetaminophen (APAP).Results: The oral administration of APAP significantly altered the levels of hepatic and renal damage indicators in Wistar rats. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-s-transferase (GST) and total thiols (TTH) decreased significantly in erythrocytes, hepatic and renal tissues. Administration of B. ciliata (150 mg/kg BW) significantly decreased the elevated hepato-renal biomarkers and malondialdehyde (MDA) levels in the tissues whereas significantly increased the levels of SOD, GST and TTH in erythrocytes and liver. The higher dose of B. ciliata (300 mg/kg BW) restored the levels of plasma hepatic and renal biomarkers as well as antioxidant parameters (SOD, GST, GPx, TTH and MDA). It also reversed the histopathological alterations in hepato-renal tissues indicating the protective potential of the extract.Conclusions: Overall, the results indicated that the B. ciliata rhizome extract attenuated the drug-induced hepato-renal toxicity in a dose-dependent manner in Wistar rats and therefore, has the potential for future therapeutic uses.

WITHDRAWN: Curcuma longa alone and in combination with pioglitazone attenuates paraquat-induced lung injury in rats through improving inflammation, oxidative stress and fibrosis

Background and aimThe therapeutic effects of pioglitazone (Pio), dexamethasone (Dexa) and Curcuma longa (Cl) on inhaled paraquat (PQ)-induced lung oxidative stress, inflammation, pathology changes and tracheal responsiveness were evaluated. Experimental procedureOne group of rats was exposed to saline (group C) and six groups to PQ aerosols. One group of PQ-exposed rats was given drinking water alone (group PQ), while other groups were received drinking water containing; two doses of Cl. (150 and 600 mg/kg, Cl-L and Cl–H), Pio (5 mg/kg), Pio + Cl-L and Daxa (0.03 mg/kg), (7 rat in each group). Results and conclusionIn PQ group, total and differential WBC counts, malondialdehyde (MDA) in the BALF, cytokine levels (INF-γ and IL-10), lung pathological changes and TR were remarkably increased but the BALF thiol, catalase (CAT) and superoxide dismutase (SOD) levels were reduced (for interstitial necrosis, p < 0.05 and for other cases, p < 0.001). Treatment of rats with Cl–H and Pio + Cl-L, significantly improved all measured variables, treatment with Pio and Cl-L improved most variables and treatment with Pio only few variables (p < 0.05 to p < 0.01). The improvements in almost all variables (except some pathological changes) in the Pio + Cl-L group were significantly higher than the Pio and Cl-L groups alone (p < 0.05 to p < 0.001).Curcuma longa ameliorated lung damage induced by inhaled PQ similar to dexamethasone and Pio and a synergic effect between Cl and Pio was observed, suggesting, amplified the activation effects of Pio on PPARs by Cl.