Tissue Glutathione Research Articles

High-casein diet restores the redox balance in the liver and pancreatic health of mice when exposed to radiation during call mode from mobile phones

Introduction: The current lives of human beings cannot be imagined without cellular phones and electronic gadgets. Still, the probabilityof being exposed to their harmful radiation is unabated which demands an immediate intervention to shield humankind from beingaffected by using such devices. In our current investigation, we aimed to check the role of a high-casein diet as a protective measureagainst the biological effects of electromagnetic radiation (EMR) emerging from mobile phones on hepatic and pancreatic systemsMethods: Swiss albino mice (n=24) were fed on a standard laboratory diet (ND; n=12) and an isocaloric high-casein diet (HCD; n=12).Six mice from each dietary group were exposed to mobile phone radiation for 3 hours/day within a 3 months span. Histopathologicalalterations were studied in hepatic and pancreatic tissues by using Periodic acid-Schiff (PAS)-hematoxylin and routine H&E stainingmethods. Biochemical evaluation of total serum protein, lipid profile and glucose, total glutathione, oxidized glutathione, and antioxidantenzymatic activities of hepatic tissues were performed. Results: Hyperglycemia was noticeable along with a reduced number and areaof islets of Langerhans in radiation-exposed mice when compared to other groups. This was supported by the observation of depletedglycogen reserves in their liver. Additionally, distorted hepatic morphology with nuclear degeneration was suggestive of apoptoticprogression. The total glutathione pool was reduced on radiation exposure, hint at redox imbalance. HCD was competent in preservingthe normal pancreas and liver functioning in radiation-exposed mice.

Engineering Multifunctional Thylakoid as an Oxygen Self-Supplying Photosensitizer for Esophageal Squamous Cell Carcinoma-Targeted Photodynamic Therapy

Open AccessCCS ChemistryRESEARCH ARTICLES19 Dec 2022Engineering multifunctional thylakoid as an oxygen self-suppling photosensitizer for esophageal squamous cell carcinoma-targeted photodynamic therapy Yingqiu Qi, Hui Wang, Anni Du, Chen Liu, Xiaofan Sun, Xiaocao Meng, Jinxiu Shen, Sai-Yang Zhang, Li-Rong Zhang, Bing Jiang, Guangjun Nie and Huan Min Yingqiu Qi Google Scholar More articles by this author , Hui Wang Google Scholar More articles by this author , Anni Du Google Scholar More articles by this author , Chen Liu Google Scholar More articles by this author , Xiaofan Sun Google Scholar More articles by this author , Xiaocao Meng Google Scholar More articles by this author , Jinxiu Shen Google Scholar More articles by this author , Sai-Yang Zhang Google Scholar More articles by this author , Li-Rong Zhang Google Scholar More articles by this author , Bing Jiang Google Scholar More articles by this author , Guangjun Nie Google Scholar More articles by this author and Huan Min Google Scholar More articles by this author https://doi.org/10.31635/ccschem.022.202202404 SectionsSupplemental MaterialAboutPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Photodynamic therapy (PDT) has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma (ESCC). However, the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery, insufficient oxygen supply and neutralization by excessive glutathione (GSH) in tumor tissue. Herein, an engineered multifunctional thylakoid nanostructure, [email protected]@GA (abbreviated as TEPG), composed of a thylakoid membrane (TM) and ESCC cell membrane (EM)-fused biomembrane shell (TM-EM) and gambogic acid (GA)-loaded poly (lactic-co-glycolic acid) nanocore, was designed for enhanced PDT for ESCC. When fused with EM, TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage. The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue. Moreover, when TEPG was selectively internalized by ESCC cells, GA was released to consume the excessive intracellular GSH. Under infrared irradiation, the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG. An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation. This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC. Download figure Download PowerPoint Previous articleNext article FiguresReferencesRelatedDetails Issue AssignmentNot Yet AssignedSupporting Information Copyright & Permissions© 2022 Chinese Chemical Society Downloaded 50 times PDF downloadLoading ...

Hepatoprotective Effect of Vitamin B12 in Acetaminophen Induce Hepatotoxicity in Male Rats.

Acetaminophen is a pharmaceutical synthesized non-opioid analgesic that belongs to the "aniline analgesics" class of medicine. Because it lacks a significant anti-inflammatory effect, it is not classified as a non-steroidal anti-inflammatory therapeutic medication (NSAID). As an over-the-counter pain reliever and antipyretic, Acetaminophen is the active metabolite of phenacetin and acetanilide, but it is less toxic than either precursor. According to some medical studies, Acetaminophen toxicity can be treated with vitamin B12. Acetaminophen-poisoned Male Wister rats were the subject model of the current study, which examines the effects of vitamin B12 on their hepatic health. There were three groups of animals: Acetaminophen treated animals (750 ml/kg), vitamin B12-treated animals (0.63 g/kg), and a control group that received distilled water (750 ml/kg). All animals were given oral medication for seven days. On the seventh day, the animal was sacrificed. Plasma levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Glutathione (GSH), total antioxidant capacity (TAC), Caspase3, Malondialdehyde (MDA), Interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-) were measured in the cardiac blood samples. Vitamin B12 lowers liver enzyme levels in the blood, increases overall antioxidant levels, and compensates for tissue glutathione deficiency while lowering serum elevations. TNF-α and interleukin-6 levels are also reduced by caspase3. Acetaminophen-induced hepatic necrosis and inflammatory cell infiltration were both considerably reduced by vitamin B12 supplementation. According to this study, vitamin B12 was found to have a protective effect against acetaminophen-induced hepatotoxicity.

Protective effects of melatonin against physical injuries to testicular tissue: A systematic review and meta-analysis of animal models.

Modern societies face infertility as a global challenge. There are certain environmental conditions and disorders that damage testicular tissue and may cause male infertility. Melatonin, as a potential antioxidant, may protect testicular tissue. Therefore, we conducted this systematic review and meta-analysis to evaluate the effects of melatonin in animal models against physical, heat, and ischemic damage to the testicular tissue. PubMed, Scopus, and Web of Science were systematically searched to identify animal trials evaluating the protective effect of melatonin therapy on rodent testicular tissue when it is exposed to physical, thermal, ischemic, or hypobaric oxygen stress. Random-effect modeling was used to estimate the standardized mean difference and 95% confidence intervals based on the pooled data. Additionally, the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool was used to assess the risk of bias. The study protocol was prospectively registered in PROSPERO (CRD42022354599). A total of 41 studies were eligible for review out of 10039 records. Studies employed direct heat, cryptorchidism, varicocele, torsion-detorsion, testicular vascular occlusion, hypobaric hypoxia, ischemia-reperfusion, stress by excessive or restraint activity, spinal cord injury, and trauma to induce stress in the subjects. The histopathological characteristics of testicular tissue were generally improved in rodents by melatonin therapy. Based on the pooled data, sperm count, morphology, forward motility, viability, Johnsen's biopsy score, testicular tissue glutathione peroxidase, and superoxide dismutase levels were higher in the melatonin treatment rodent arms. In contrast, the malondialdehyde level in testicular tissue was lower in the treatment rodent arms. The included studies suffered from a high risk of bias in most of the SYRCLE domains. This study concludes that melatonin therapy was associated with improved testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress in male rodents with physical, ischemic, and thermal testicular injuries. In this regard, melatonin deserves scientific investigations as a potential protective drug against rodent male infertility. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354599.

Protective effects of melatonin against the toxic effects of environmental pollutants and heavy metals on testicular tissue: A systematic review and meta-analysis of animal studies.

Environmental pollution and infertility are two modern global challenges that agonize personal and public health. The causal relationship between these two deserves scientific efforts to intervene. It is believed that melatonin maintains antioxidant properties and may be utilized to protect the testicular tissue from oxidant effects caused by toxic materials. A systematic literature search was conducted in PubMed, Scopus, and Web of Science to identify the animal trial studies that evaluated melatonin therapy's effects on rodents' testicular tissue against oxidative stress caused by heavy metal and non-heavy metal environmental pollutants. Data were pooled, and standardized mean difference and 95% confidence intervals were estimated using the random-effect model. Also, the risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool. (PROSPERO: CRD42022369872). Out of 10039 records, 38 studies were eligible for the review, of which 31 were included in the meta-analysis. Most of them showed beneficial effects of melatonin therapy on testicular tissue histopathology. [20 toxic materials were evaluated in this review, including arsenic, lead, hexavalent chromium, cadmium, potassium dichromate, sodium fluoride, cigarette smoke, formaldehyde, carbon tetrachloride (CCl4), 2-Bromopropane, bisphenol A, thioacetamide, bisphenol S, ochratoxin A, nicotine, diazinon, Bis(2-ethylhexyl) phthalate (DEHP), Chlorpyrifos (CPF), nonylphenol, and acetamiprid.] The pooled results showed that melatonin therapy increased sperm count, motility, viability and body and testicular weights, germinal epithelial height, Johnsen's biopsy score, epididymis weight, seminiferous tubular diameter, serum testosterone, and luteinizing hormone levels, testicular tissue Malondialdehyde, glutathione peroxidase, superoxide dismutase, and glutathione levels. On the other hand, abnormal sperm morphology, apoptotic index, and testicular tissue nitric oxide were lower in the melatonin therapy arms. The included studies presented a high risk of bias in most SYRCLE domains. In conclusion, our study demonstrated amelioration of testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress. Melatonin deserves scientific attention as a potential therapeutic agent for male infertility. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022369872.

Fullerene C60 Attenuates Heart Tissue Inflammation by Modulating COX-2 and TNF-Alpha Signaling Pathways in DMBA Induced Breast Cancer in Rats.

The present study aimed to investigate the therapeutic effect of fullerene C60 nanoparticle against heart tissue damage caused by 7,12-dimethylbenz [a] anthracene (DMBA) in female rats. Female Wistar albino rats, 8weeks old (n = 60) weighing around (150 ± 10g) were used for the study. These rats were divided into 4 groups and each group included 15 rats. Groups: (i) Control Group: Fed with standard diet; (ii) C60 Group: C60 (1.7mg/kg bw, oral gavage); (iii) DMBA Group: DMBA (45mg/kg bw, oral gavage); (iv) C60 and DMBA Group: C60 (1.7mg/kg bw, oral gavage) and DMBA (45mg/kg bw, oral gavage) group. Malondialdehyde (MDA) analysis, catalase activity (CAT), and glutathione (GSH) in heart tissue were determined by spectrophotometer. In addition, heart tissue DNA damage was investigated. Caspase-3, p53, HO-1, COX-2, and TNF-α protein expression levels in heart tissue were determined by western blotting. As a result, Caspase-3, p53, HO-1 protein expression, GSHlevels and CAT activity increased, COX-2, TNF-α protein expression, and MDA levels were significantly decreased in the C60 + DMBAgroup compared to the DMBAgroup. Therefore, the fullerene C60 nanoparticle may be a promising and effective therapy for the treatment of heart diseases associated with inflammation.

Technical note: simultaneous determination of amino thiols in pig tissue by ultra-high performance liquid chromatography with fluorescence detection.

Sulfur amino acid nutrition and metabolism are linked to animal disease. While validated methods for the determination of amino thiol levels in plasma or serum are available, there is a dearth of validated methods for their measurement in tissue. A robust and reproducible ultra-high performance liquid chromatography method has been validated for the simultaneous determination of concentrations of cysteine (Cys), cysteinylglycine (CysGly), homocysteine (Hcys), γ-glutamylcysteine (γ-GluCys), and glutathione (GSH) in pig tissue. Tissue was homogenized and deproteinized with trichloroacetic acid. Amino thiols in the acid-soluble fraction of the tissue homogenate were reduced with tris-(2-carboxyethyl)-phosphine hydrochloride and derivatized with 4-(aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (ABD-F). Amino thiols were resolved under reversed-phase gradient conditions on a Waters Acquity BEH C18 column (1.7 µm, 2.1 mm × 100 mm) within 4.5 min and detected with fluorescence. The peak area ratio of analyte to 2-mercaptopropionylglycine internal standard, added to external calibration standards and samples, was used to develop linear calibration curves. Linear calibrations were performed over the range of 15-1,500 nmol/g for Cys, CysGly, Hcys, and γ-GluCys and 150-15,000 nmol/g for GSH. Linearity, lower limit of detection, lower limit of quantitation, accuracy, precision, sample stability, and carryover were evaluated. We demonstrate excellent linearity for all analytes within their respective concentration range (r2 > 0.99) and excellent recovery of amino thiols from spiked samples (mean ± SD across tissues; Cys, 100.0 ± 2.2%; CysGly, 95.4 ± 5.1%; Hcys, 96.6 ± 2.0%; γ-GluCys, 102.2 ± 2.7%; and GSH, 100.6 ± 3.3%). The intra-day and inter-day precisions did not exceed 5% and 10%, respectively. Repeated freezing and thawing of tissue homogenate did not affect measured amino thiol concentrations, ABD-labeled amino thiols were stable for 1 wk after derivatization, and there was no sample carryover across consecutive injections. We confirm the identity of each ABD-labeled amino thiol with Orbitrap mass spectrometry. Finally, we apply the method to the determination of amino thiol concentrations in liver and jejunum tissues in newly weaned pigs and show that despite elevated Cys and maintained GSH concentrations in liver, both γ-GluCys and GSH decline in jejunum of weaned pigs.

Hispidulin protective impact on sepsis induced acute kidney injury is mediated by regulation of AKT and NF-κB pathway

Sepsis-induced acute kidney injury is associated with inflammatory dysregulations within the kidney. This study aimed to explore the renal protective effect of hispidulin on suppressing the apoptosis rate, and inhibiting reactive oxygen species production and inflammatory response after cecal puncture (CLP) operation. In order to gain a deeper understanding of the relationship between sepsis and acute kidney injury, the CLP induced kidney injury animal model was established. The automated biochemical analyzer was used to measure the kidney function related biomarkers including serum cystatin C (ScysC), blood urea nitrogen (BUN), and serum creatinine (Scr). The pathological changes of damaged kidney tissues were detected by hematoxylin and eosin (H&E) staining. The expression of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6) were detected by their corresponding test kits and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). The level of reactive oxygen species production-related protein including myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in kidney tissue from each group were quantized using Enzyme-linked immunosorbent assay (ELISA). The protein expression was measured using western blot and the apoptotic rate of kidney tissue was measured by terminal deoxynucleotidyl transferase Deoxyuridine Triphosphate (dUTP) nick end labeling (TUNEL) assay. Our results revealed that hispidulin has the protective ability in sepsis-induced acute kidney injury. The potential mechanism of hispidulin on sepsis-induced cell apoptosis, oxidative stress and inflammatory response was also investigated. Finally, our results highlighted that hispidulin exerted a protective effects on CLP-induced acute kidney injury by suppressing the protein kinase B (AKT) and Nuclear factor kappa B (NF-κB) signaling pathways. In summary, the current study provided a piece of novel evidence, that hispidulin can be explored as a potential drug in CLP-induced acute kidney injury by examining its effects on suppressed the oxidative stress, inflammatory responses, and apoptosis in kidney tissue.

Extraction of echinacoside from Cistanche tubulosa (Schenk) R. Wight and investigation of its protective effect on liver injury in sepsis rats

In this study, echinacoside was extracted from Cistanche tubulosa (Schenk) R. Wight, and its protective effect on liver injury in sepsis rats was investigated. Forty-five rats were randomly divided into control, sepsis and echinacoside groups, 15 rats in each group. The sepsis model was established in sepsis and echinacoside groups. In echinacoside group, the rats were treated with echinacoside at 1 h before modeling. At 24 h after modeling, compared with sepsis group, in echinacoside group the serum aspartate aminotransferase and alanine aminotransferase levels were decreased, the liver injury score and hepatocyte apoptosis rate were decreased, the serum monocyte chemoattractant protein-1, tumor necrosis factor α, interleukin 6 and interleukin 1β levels were decreased, the liver tissue catalase, superoxide dismutase and glutathione peroxidase levels were increased, the liver tissue malondialdehyde level was decreased, and the liver tissue nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein expression levels were increased. The difference of all above comparisons was significant (P < 0.05). In conclusion, echinacoside can inhibit the inflammatory response, activate the Nrf2/HO-1 signal pathway, and reduce the oxidative stress, thus alleviating the liver injury in sepsis rats.

Effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/PPARγ pathway in arrhythmic rats

This paper aimed to investigate the effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/peroxisome proliferator-activated receptor γ(PPARγ) pathway in arrhythmic rats. SD rats were randomly divided into a control group, a model group, a low-dose(20 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a medium-dose(40 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a high-dose(80 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a propranolol hydrochloride(2 mg·kg~(-1)) group, with 12 rats in each group. Except the control group, rats in other groups were prepared as models of arrhythmia by sublingual injection of 1 mL·kg~(-1) of 0.002% aconitine. After grouping and intervention with drugs, the arrhythmia, myocardial cells apoptosis, myocardial tissue glutathione peroxidase(GSH-Px), catalase(CAT), malondialdehyde(MDA), serum interleukin-6(IL-6), prostaglandin E2(PGE2) levels, myocardial tissue apoptosis, and Wnt/β-catenin/PPARγ pathway-related protein expression of rats in each group were measured. As compared with the control group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA levels in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels increased significantly in the model group, whereas the GSH-Px and CAT levels, and Bcl-2 and PPARγ protein expression levels in myocardial tissues reduced significantly. As compared with the model group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA leve in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels reduced in the drug intervention groups, whereas the GSH-Px and CAT levels and Bcl-2 and PPARγ protein expression levels in myocardial tissues increased. The groups of total flavonoids of buckwheat flower and leaf were in a dose-dependent manner. There was no significant difference in the levels of each index in rats between the propranolol hydrochloride group and the high-dose group of total flavonoids of buckwheat flower and leaf. The total flavonoids of buckwheat flower and leaf inhibit the activation of Wnt/β-catenin pathway, up-regulate the expression of PPARγ, reduce oxidative stress and inflammatory damage in myocardial tissues of arrhythmic rats, reduce myocardial cell apoptosis, and improve the symptoms of arrhythmia in rats.

Ammonia toxicity in Nile tilapia: Potential role of dietary baicalin on biochemical profile, antioxidant status and inflammatory gene expression

The privileges of dietary baicalin intervention as a prophylaxis were assessed in Nile tilapia (Oreochromis niloticus) pre and post-acute ammonia challenge. The experimental trial lasted for 4 weeks, the first group served as a control (fed a basal diet), while, the second group received diet supplemented with baicalin (0.8 g/kg diet). The third group was fed a basal diet and exposed to acute ammonia toxicity in the last week. Meanwhile, the fourth group fed diet supplemented with baicalin (0.8 g/kg diet), then exposed to unionized ammonia challenge (5 mg/L) in the last week. Dietary baicalin notably augmented immune indicators (lysozyme, respiratory burst activity, phagocytic activity assay, and immunoglobulin (Ig) and tissue antioxidant biomarkers (total antioxidant capacity (TAC), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)). Meanwhile, it decreased malondialdehyde (MDA), hepato-renal indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, uric acid, creatinine), and stress indicators including glucose, cholesterol, triglycerides, and cortisol. Ammonia exposure significantly elevated stress parameters and MDA, but lessened SOD, GSH, CAT, and TAC levels in liver, gills, and kidneys tissue. Dietary baicalin and ammonia exposure induced interaction impacts on urea, creatinine, cortisol, glucose, lysozyme, alanine aminotransferase (ALT), aspartate aminotransferase (AST). Prior to ammonia exposure, baicalin administration clearly decreased urea. Fish fed enriched diet with - baicalin showed no changes in stress biomarkers before ammonia exposure, meanwhile reduced it after the ammonia challenge. Dietary baicalin alleviated fluctuations induced by ammonia in all above-mentioned parameters. And alleviated the altered gene expression for Hsp70, Nf-κB, Myd88, traf6, Nrf2, Ho-1, Il-1β, Il-8, TNF-α, and TLR-4 induced by ammonia toxicity. Taken together, it has been recommended to use baicalin for 3 weeks to mitigate ammonia-induced-oxidative damage, immune impairment, stress condition, hepato-renal failure, antioxidant and inflammatory gene expression in O. niloticus.

Investigating the protective effects of cinnamon bark hydroalcoholic extract on the inhibition of liver damage induced by rifampin in male Wistar rats

Introduction: Rifampin is one of the common drugs used to treat tuberculosis and is considered a strong toxic agent for the liver. The aim of this study is to investigate the effects of cinnamon extract administration on rifampin-induced hepatotoxicity in rats. Materials and methods: In this experimental study, 60 male Wistar rats were randomly divided into 6 groups. Liver damage and induction of oxidative stress were caused by administration of 80 mg/kg/day rifampin. Different doses of cinnamon extract (50, 100 and 200 mg/kg) were administered to sick mice by daily gavage in three experimental groups. Liver damage caused by rifampin was evaluated by examining serum biochemical factors as well as the amount of reactive oxygen species, glutathione, antioxidant capacity, lipid peroxidation and histopathological changes in liver tissue. Data analysis was done using Prism version 6 software and one-way analysis of variance and Tukey's post hoc test. Results: The administration of rifampin at the rate of 80 mg/kg for 21 consecutive days caused liver damage (P&lt;0.05). On the other hand, administration of different doses of cinnamon extract could significantly improve the liver damage caused by rifampin consumption (P&lt;0.05) Discussion and conclusion: According to the results of this study, cinnamon extract with antioxidant properties protects the liver against oxidative damage caused by rifampin. These healing effects were shown in the form of reduction of liver damage markers in serum, reduction of oxidative stress markers and improvement of liver tissue damage.

Ulva fasciata, a green alga, attenuates the kidney and liver dysfunctions in rats induced by acetaminophen

Acetaminophen (AAP) is an analgesic–antipyretic drug which is considered safe at recommended dose, but its overuse may induce renal and hepatic injuries. Marine macro algae have great potential against drug-induced renal and hepatic dysfunctions. The present study described the reno-protective and hepato-protective effects of the ethanol extract of an edible green alga Ulva fasciata and its fractions (n-hexane, chloroform and methanol) against AAP toxicity. In the 1st set of experiment, rats were divided into five groups. Of which two were treatment groups beside three controls, the first treatment group was given ethanol extract of U. fasciata alone and the second group was given the same extract with AAP. In the 2nd set of experiment, rats were divided into nine groups, of which three treatment groups administered n-hexane, chloroform and methanol fractions of ethanol extract of U. fasciata respectively while other three treatment groups received the same fractions individually with AAP. On the 11th day, rats were decapitated after 12 h of fasting from both sets, blood samples were collected for assessment of biochemical parameters and kidney tissues were used for determination of oxidants and antioxidants. Histopathological assessment was also done in kidney tissues. A single dose of AAP (600 mg/kg) affected kidney markers including creatinine, urea and blood urea nitrogen (BUN) and hepatic enzymes. Ethanolic extract of U. fasciata normalized kidney and liver markers in AAP intoxicated rats. AAP also reduced glutathione (GSH) in kidney tissues and altered kidney architecture, which were improved by ethanolic extract and chloroform soluble fraction of U. fasciata. A total of 14 polyunsaturated fatty acids were identified from chloroform soluble fraction of U. fasciata by GC-MS and assumed these may be involved in protective activities of U. fasciata.

Fingolimod attenuates ovalbumin-induced airway inflammation via inhibiting MAPK/ERK signaling in mice.

The current study was designed to investigate the potential anti-inflammatory and antioxidant effects of fingolimod against Ovalbumin (Ova)-induced allergic airway inflammation compared to dexamethasone. Fingolimod was given (0.5 mg/kg/day, p.o.) for sensitized mice 1 hbefore Ova challenge from Days 19 to 24. Fingolimod significantly inhibited Ova-induced elevation of inflammatory cells and eosinophils numbers in bronchoalveolar lavage fluid(BALF) and reduced concentrations of immunoglobulin E in serum and of sphingosine-1-phosphate, interleukin(IL)-4, and IL-13 in BALF. Fingolimod inhibited microvascular leakage and edema as reflected by the decreased lung/body weight index. These findings were supported by histopathological examination results showing that fingolimod substantially decreased perivascular edema and inflammatory cell infiltration. Fingolimod also attenuated Ova-induced oxidative stress as evidenced by decreased malondialdehyde concentration along with increasing concentrations of reduced glutathione and superoxide dismutase in lung tissues. Fingolimod also significantly decreased monocyte chemoattractant protein-1(MCP-1), p-ERK,and p-P38 in lung tissues of Ova-challenged mice. In conclusion, the current study demonstrated the anti-inflammatory and antioxidant effects of fingolimod in allergic airway inflammation that might be associated with the downregulation of mitogen activated kinases signaling to decrease T helper 2 cytokine secretion (IL-4 and IL-13) and MCP-1 expression, along with the inhibition of oxidative stress.

LCZ696 protects against doxorubicin-induced cardiotoxicity by inhibiting ferroptosis via AKT/SIRT3/SOD2 signaling pathway activation.

Doxorubicin (DOX) is an effective and widely used anticancer drug but has limited clinical applicability because of its cardiotoxicity. Ferroptosis plays a key role in DOX-induced cardiac damage and cardiomyocyte cell death. The inhibition of ferroptosis reverses DOX-induced cardiotoxicity (DIC). LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, protects against DIC. However, the mechanism of action of LCZ696, especially its effect on ferroptosis, is incompletely understood. This study investigates the cardioprotective effects of LCZ696 on DIC in vivo and in vitro.Cardiotoxicity was induced in Wistar rats by tail intravenous injection of 2.5mg/kg DOX once a week for six weeks. Rats and H9c2 cells were treated with or without LCZ696 to determine the cardioprotective role and underlying mechanisms of LCZ696 against DIC. To assess the role of SIRT3 and correlated pathways in ferroptosis, SIRT3 knockout was performed using lentiviral vectors, and AKT was inhibited with LY294002. LCZ696 significantly attenuated DIC by decreasing the concentrations of lipid reactive oxygen species and malondialdehyde and increasing the levels of glutathione peroxidase-4 and reduced glutathione in cells and heart tissues. Moreover, LCZ696 remodeled myocardial structures and improved heart ventricular function in DOX-treated rats. LCZ696 treatment increased SIRT3 expression and deacetylated its target gene SOD2, and these changes were mediated by AKT activation. SIRT3 knockdown and AKT inhibition induced lipid peroxidation and reduced the protective effect of LCZ696 in H9c2 cells. Collectively,LCZ696 prevents DIC by inhibiting ferroptosis via AKT/SIRT3/SOD2 signaling pathway activation. Thus, LZC696 is a potential therapeutic strategy for DIC.

Effects of BPZ, BPC, BPF, and BPS Exposure on Adult Zebrafish (Danio rerio): Accumulation, Oxidative Stress, and Gene Expression

As substitutes for bisphenol A (BPA), bisphenol analogs (BPs) have been found to cause endocrine disorders and induce toxic effects. The objective of this study was to evaluate the bioaccumulation and subacute toxicity of bisphenol Z (BPZ), bisphenol C (BPC), bisphenol F (BPF), and bisphenol S (BPS) to zebrafish. Five-month-old zebrafish were exposed to 1/100 LC50, 1/50 LC50, and 1/10 LC50 of BPZ, BPC, BPF, and BPS for 13 days, respectively. Bioaccumulation, oxidative stress, and related mRNA expression in zebrafish tissues were measured on days 1, 7, and 13. After exposure, the four kinds of BPs all resulted in the accumulation of concentration and lipid peroxidation in zebrafish tissues to varying degrees. BPZ and BPC had the highest bioaccumulation level and had the greatest influence on malonic dialdehyde (MDA). In addition, the enzyme activities of superoxide dismutase (SOD), peroxidase (POD), glutathione peroxidase (GSH-PX), and the content of glutathione (GSH) in zebrafish tissues were also affected at different levels. However, the enzyme activities of SOD and POD were inactivated in zebrafish exposed to a high concentration of BPC. Further studies showed that BPs exposure down-regulated the transcription level of sod but up-regulated the relative expression levels of cat and gpx. The mRNA relative expression level of erα was not significantly changed, while the mRNA relative expression level of erβ1 was significantly down-regulated except under BPS exposure. These results indicate that BPZ, BPC, and BPF significantly affect the expression level of the estrogen receptor (ER) in zebrafish tissues. Overall, the results suggest that exposure to waterborne BPs can cause severe oxidative stress and tissue damage in adult zebrafish that is not sufficient to kill them after 13 days of waterborne exposure. The toxicity of BPs to organisms, therefore, should be further analyzed and evaluated.

Therapeutic effect of Jingfang Granules on CCl_4-induced liver fibrosis in mice and its mechanism

To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg·kg~(-1))+CCl_4, a Jingfang high-dose(16 g·kg~(-1)) group, a Jingfang high-dose(16 g·kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g·kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g·kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL·kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL·kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1β(IL-1β) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-β(TGF-β), α-smooth muscle actin(α-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-α, IL-6, and IL-1β in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-β, α-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-β/Smad4 signaling pathway.

Preventive effect of salmon sperm DNA on acute carbon tetrachloride-induced liver injury in mice through Nrf2/ARE and mitochondrial apoptosis pathway.

Liver injury refers to the damage of liver function, which will seriously harm the body's health if it is not prevented and treated in time. Sporadic researches have reported that ingestion of DNA has a hepatoprotective effect, but its effect and mechanism were not clarified. The purpose of this study was to explore the preventive effect and mechanism of salmon sperm DNA on acute liver injury in mice induced by carbon tetrachloride (CCl4). Six-week-old ICR (Institute of Cancer Research) male mice were used to establish a liver injury model by injecting with 4% CCl4, silymarin, and three different concentrations of DNA solutions were given to mice by gavage for 14 days. The histological and pathological changes in the liver were observed. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and the levels of oxidative and antioxidant markers such as malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) in liver tissue were determined. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA), and hepatic oxidative stress and apoptosis-related markers were determined by western blotting. The results showed that compared with the model group, the DNA test group significantly improved the liver pathological changes and the level of liver function, regulated liver oxidative stress, reduced hepatocyte apoptosis, and decreased the levels of inflammatory factors such as TNF-α and IL-6. Compared with the silymarin group, the high dose of DNA was even more effective in preventing liver injury. In conclusion, salmon sperm DNA has a potential protective effect against acute liver injury induced by CCl4, which is achieved by regulating the Nrf2/ARE (nuclear factor erythroid 2 (NF-E2)-related factor 2/antioxidant responsive element) oxidative stress pathway and mitochondrial apoptosis pathway.

Comparative Analysis of Antioxidant Accumulation under Cold Acclimation, Deacclimation and Reacclimation in Winter Wheat.

Low temperature during cold acclimation (CA) leads to the accumulation of detrimental reactive oxygen species (ROS) in plant tissues, which are scavenged by antioxidants, such as ascorbate and glutathione. However, there is a lack of studies examining the dynamics of antioxidants throughout CA, deacclimation (DEA), and reacclimation (REA) in winter wheat. Six winter wheat genotypes were selected to assess the effect of CA, DEA, and REA on the concentrations of ascorbate and glutathione in leaf and crown tissues under two CA temperature treatments. Higher levels of total, reduced, and oxidised ascorbate were determined in leaves, whereas crowns accumulated higher concentrations of nicotinamide adenine dinucleotide (NAD+) after CA, DEA, and REA. Constant low temperature (CLT) during CA led to higher contents of ascorbate and glutathione in both tissues at all stages of acclimation, in comparison with prolonged higher low temperature (PHLT). The concentrations of antioxidants increased after CA, tended to decrease after DEA, and returned to CA levels after REA. Significant positive correlations between freezing tolerance (FT) and antioxidants were only determined under the CA at CLT treatment, thus, affirming the negative effect of PHLT during CA on the FT of winter wheat.

Early Monitoring of Redox Status Based on Reduced Molecules Using In Vivo DNP-MRI for Cancer Treatment

<h3>Purpose/Objective(s)</h3> Radiation treatment effectiveness is assessed through the observation of morphological changes with CT or MRI images after treatment. The treatment efficacy of radiotherapy depends on redox modulation in tumor tissue, such as hydroxyl radicals and of reactive oxygen species generated by irradiation. Therefore, redox status may be a prognostic factor response to radiotherapy. However, spatiotemporal response of the redox metabolism in tumor tissue post-irradiation remains unknown. The purpose of this study was to detect early changes in the redox status in tumor tissue after irradiation using <i>in vivo</i> dynamic nuclear polarization (DNP)-MRI, to clarify the key molecules that cause these changes, and to compare these changes with early changes in lactate metabolism using hyperpolarized ¹³C magnetic resonance spectroscopy (MRS). <h3>Materials/Methods</h3> To monitor the response of tumor redox status after irradiation, redox imaging using in vivo DNP MRI/ Carbamoyl PROXYL (CmP) as redox sensitive DNP probe was performed after 5 Gy irradiation. To clarify the relationship between redox status alteration and treatment efficacy, in vivo DNP MRI was performed before and after irradiation by 2 and 5 Gy. In addition, tissue GSH and AsA levels on day 1 post irradiation were determined by HPLC. To observe the Warburg effect after radiation treatment, dissolution DNP study using hyperpolarized ¹³C pyruvate was performed before and after irradiation. <h3>Results</h3> The DNP image intensity in the tumor demonstrated a maximum value approximately four minutes after CmP administration, thereafter the image intensity was decreased by the redox reaction. The tumor GSH and AsA level on day 1 post irradiation were decreased compared to the control group. Production of hyperpolarized ¹³C lactate in tumor tissue did not change before and after irradiation. <h3>Conclusion</h3> Our study highlights that redox status in tumor tissue is already significantly decreased on day 1 before the detection of any morphological changes, even after irradiation with a dose as low as 2 Gy. Early changes in this redox status may be related decreases in glutathione and ascorbic acid levels in the tumor tissue after irradiation, which may alter earlier than ¹³C pyruvate hyperpolarized MRS, based on lactate metabolism. Therefore, early assessment of change in decay rate using in vivo DNP-MRI/CmP probing may predict the subsequent radiotherapy effect.