N-acetylcysteine Research Articles

Navigating laboratory investigations for an accurate assessment of community-acquired pneumonia: Case report

According to recent findings, demographic characteristics, seasonal fluctuations, and geographic regions are factors for the community-acquired pneumonia. Community acquired pneumonia is a non-hospital acquired lung parenchymal infection caused by gram-negative bacteria “Pseudomonas aeruginosa” which is transmitted through inhaling infected droplets. Here, we are reporting a case of geriatric patient with chief complaints of cough in the past 20 days, shortness of breath, tachycardia, tachypnoea, fever, and chest pain from 10 days. physician was suggested go for further investigations and lab reports like complete blood picture count, ESR test, sputum culture test and radiographic findings like Chest X-ray, chest computed tomography. Standard treatment includes antibiotics like Levofloxacin, Azithromycin and antihypertensive like Telmisartan, and mucolytics like Ambroxol syrup and other medications like N-Acetyl Cysteine, levocetirizine. If early diagnosis and early treatment were initiated, then the progression of diseases would have been stopped and then the Patient was discharged with stable condition, but she must come for the follow-up sessions like OP sessions. If the patient follows the life-style modifications and precautions like practice good hygiene, take enough rest, consume healthy diet, the quality of life will be improved.

Identification of Nicotinic Acetylcholine Receptor for N-Acetylcysteine to Rescue Nicotine-induced Injury Using BeatingCilia in Primary Tissue Derived Airway Organoids.

Smoking is one of the major contributors to airway injuries. N-acetylcysteine (NAC) has been proposed as a treatment or preventive measure for such injuries. However, the exact nature of the smoking-induced injury and the protective mechanism of NAC are not yet fully understood. Here, patient tissue-derived airway organoids for modeling smoking-induced injury, therapeutic investigation, and mechanism studies are developed. Airway organoids consist mainly of ciliated cells, together with basal cells, goblet cells, and myofibroblast-like cells. The organoids display apical-out and basal-in polarity and are enriched in beating cilia, which are sensitive to smoking challenge and NAC treatment. An algorithm is developed to measure ciliary beating activity by analyzing the altered beating pattern of cilia in response to nicotine challenge and NAC treatment. Nicotinic acetylcholine receptors (nAChRs) expressed by airway organoids are involved in the mechanisms of nicotine-induced injury through the nicotine-nAChR pathway. In contrast to the common understanding that NAC has an antioxidative effect that mitigates airway damage, it is elucidated that NAC binding to nicotine can abolish the binding capacity of nicotine to nAChRs and thus prevent nicotine-induced injury. This study focuses on the advances and potential of humanized organoids in understanding biological processes, mechanisms, and identifying therapeutic targets.

High-dose Intravenous N-Acetylcysteine in Mechanically Ventilated Patients with COVID-19 Pneumonia: A Propensity-Score Matched Cohort Study.

Current therapies for severe COVID-19, such as steroids and immunomodulators are associated with various side effects. N-acetylcysteine (NAC) has emerged as a potential adjunctive therapy with minimal side effects for patients with cytokine storm due to COVID-19. However, evidence supporting high-dose intravenous NAC in severe COVID-19 pneumonia requiring mechanical ventilation is limited. We conducted a retrospective analysis of consecutive patients aged ≥ 18 who were admitted for acute respiratory failure (PaO2/FiO2 ratio <300) with SARS-CoV-2 infection to the Intensive Care Unit (ICU) of Queen Elizabeth Hospital from fifth July 2020 to 31st October 2022. Inclusion was limited to patients who required mechanical ventilation. High-dose NAC refers to a dosage of 10 g per day. The primary outcome was all-cause mortality within 28 days. Propensity-score matched analysis using logistic regression was performed. Among the 136 patients analyzed, 42 (40.3%) patients received NAC. The unmatched NAC patients displayed a higher day-28 mortality (12 (28.6%) versus 4 (6.5%), p = 0.005) and fewer ventilator-free days (18.5 (0-23.0) versus 22.0 (18.3-24.0), p = 0.015). No significant differences were observed in ICU and hospital length of stays among survivors. In patients who were not treated with tocilizumab, those receiving NAC exhibited a trend toward a quicker reduction in C-reactive protein compared to those who did not receive NAC.After propensity score matching which included 64 patients with 33 (51.6%) receiving NAC, no significant differences were found in 28-day mortality, ventilator-free days, or ICU and hospital length of stay. After adjusting for potential confounders, logistic regression of the propensity score-matched population did not demonstrate that the use of NAC independently affected 28-day mortality. In patients with COVID-19 pneumonia requiring mechanical ventilation and receiving standard COVID-19 treatment, the addition of high-dose NAC did not lead to improved clinical outcomes.

Simultaneous Quantitation of Multiple Biological Thiols Using Reactive Ionization and Derivatization with Charged Mass Tags.

The biologically important thiols (cysteine, homocysteine, N-acetyl cysteine, and glutathione) are key species in redox homeostasis, and there is a clinical need to measure them rapidly, accurately, and simultaneously at low levels in complex biofluids. The solution to the challenge presented here is based on a new derivatizing reagent that combines a thiol-selective unit to optimize the chemical transformation and a precharged pyridinium unit chosen to maximize sensitivity in mass spectrometry. Derivatization is performed simultaneously with ionization ("reactive ionization"), and mass spectrometry is used to record and characterize the thiol reaction products. The method is applicable over the concentration range from 1 μM to 10 mM and is demonstrated for 25 blood serum, 1 plasma, and 3 types of tissue samples. The experiment is characterized by limited sample preparation (<4 min) and short analysis time (<1 min). High precision and accuracy (both better than 8%) are validated using independent HPLC-MS analysis. Cystine-cysteine redox homeostasis can be monitored by introducing an additional reduction step, and the accuracy and precision of these results are also validated by HPLC-MS.

Catechin promotes endoplasmic reticulum stress-mediated gastric cancer cell apoptosis via NOX4-induced reactive oxygen species.

Catechin, a polyphenolic compound in various foods and beverages, shows strong anti-cancer effects against gastric cancer (GC) cells. This study explored the effect of catechin on GC cell apoptosis and endoplasmic reticulum (ER) stress. GC cells were treated with different catechin concentrations to assess effects on cell viability, LDH release, invasion, migration, apoptosis, intracellular calcium (Ca2⁺), ER stress markers, and reactive oxygen species (ROS). siRNA knockdown targeted GRP78, PERK, CHOP, and NOX4 to examine their roles in catechin-induced ER stress and apoptosis. Catechin treatment significantly reduced GC cell viability, increased LDH release, and induced apoptosis dose-dependently. Catechins elevated intracellular Ca2⁺ and ER stress markers. Co-treatment with thapsigargin (TG) intensified these effects, implicating ER stress in apoptosis. Knocking down GRP78, PERK, and CHOP mitigated catechin-induced apoptosis and restored viability. Additionally, catechins raised ROS levels, while co-treatment with Diphenyleneiodonium (DPI) or N-acetylcysteine (NAC) lowered ROS, cell damage, and ER stress markers. NOX4 knockdown countered catechin-induced viability loss and upregulated CHOP and cleaved caspase-3. Catechin induces apoptosis in GC cells through ER stress and ROS generation. Key mediators include GRP78, PERK, CHOP, and NOX4, suggesting potential therapeutic targets for enhancing catechin efficacy in GC treatment.

Sensitive Detection of Sulfur Mustard Poisoning via N-Salicylaldehyde Naphthyl Thiourea Probe and Investigation into Detoxification Scavengers.

Sulfur mustard (SM), a blister agent and toxic chemical warfare compound, leads to injuries in the skin, eyes, and lungs, with early diagnosis being difficult because of its incubation period. Developing scavengers for sulfur mustard (SM) and its simulant, 2-chloroethylsulfide (CEES), is essential due to the severe and long-lasting toxic effects these compounds have on the human body. Existing scavengers like cysteine, sodium hydrosulfide (NaHS), and sodium thiosulfate cannot cross the blood-brain barrier (BBB), rendering them ineffective for detoxifying SM in the brain and highlighting the need for lipophilic scavengers. In this study, an N-salicylaldehyde naphthyl thiourea probe (NCrHT) was developed for detecting SM simulant CEES and its in vivo and in vitro imaging capabilities were evaluated. Additionally, the detoxification potential of scavengers was tested under similar conditions, and we introduced N-acetyl cysteine, which is lipophilic in nature, as an effective scavenger for detoxifying CEES in the zebrafish brain.

A Comparative Evaluation of the Antimicrobial Properties of 50% Grape Seed Extract, N-acetyl Cysteine and 5.25% Sodium Hypochlorite against Enterococcus faecalis (ATCC 19433) – An In vitro Study

Abstract Introduction: Endodontic infections are complex and polymicrobial, presenting significant challenges in dental treatment. Eliminating bacteria is the main objective of endodontic preparation, ensuring a tight seal to prevent reinfection. A commonly isolated bacterium, Enterococcus faecalis, is Gram positive and facultative anaerobic. It thrives in low-nutrient environments, forming resilient biofilms. Due to its tissue dissolving properties and broad-spectrum antimicrobial, sodium hypochlorite (NaOCl) is the most sought after irrigant, but its cytotoxicity is a concern. Alternatives such as grape seed extract (GSE) and N-acetyl cysteine (NAC) are being explored for their potential antimicrobial effects and biocompatibility. Materials and Methods: Forty single-rooted, non-carious premolars extracted for orthodontic reasons were selected. Teeth were cleaned, sectioned and prepared, ensuring apical patency. Specimens were autoclaved and contaminated with E. faecalis (ATCC 19433) for 30 days. Four groups (n = 10) were formed: Group I – GSE 50%, Group II – NAC 200 mg/ml, Group III – NaOCl 5.25% and Group IV – sodium chloride (0.9%). Manufacturer’s instructions were followed precisely to prep the solutions, and root canals were treated using the Reciproc R25 instrument. Samples were collected before (F1) and after (F2) instrumentation and irrigation. Colony-forming units (CFUs) were quantified and analysis was done using two-way analysis of variance and Tukey’s honestly significant difference post hoc tests, with significance set at P &lt; 0.05. Results: NaOCl significantly reduced CFU counts, demonstrating superior antimicrobial efficacy compared to NAC and GSE (P &lt; 0.01). In comparison to negative control and GSE (P &lt; 0.01), NAC showed significant antimicrobial activity, but not significantly different from GSE (P &gt; 0.05). GSE displayed potential antimicrobial properties but was less effective than NaOCl and NAC. Conclusion: NaOCl remains the most effective irrigant; however, NAC and GSE also demonstrated significant antimicrobial properties and could serve as adjuncts in endodontic therapy. Further research is needed to optimise their formulations and validate clinical applications.

Lipid-Polymer Hybrid Nanoparticles in Microparticle-Based Powder: Evaluating the Potential of Methylprednisolone Delivery for Future Lung Disease Treatment via Inhalation.

Lipid-polymer hybrid nanoparticles (LPHNPs) offer a promising method for delivering methylprednisolone (MePD) to treat lung inflammation, addressing aggregation issues seen with polymer-only formulations. This study aimed to develop LPHNPs for MePD delivery, assessing their physicochemical properties, drug loading, cytocompatibility, and release profiles, ultimately enabling inhalable microparticle-based powder. The nanoparticles were formulated using α,β-poly(N-2-hydroxyethyl)-DL-aspartamide-g-Rhodamine B-g-poly(lactic acid) (PHEA-g-RhB-g-PLA) and phospholipids DPPC, DOTAP, and DSPE-PEG2000 in a 45:30:25 weight ratio. Their size, redispersion after freeze-drying, drug loading (DL%), and controlled release were evaluated. Cytocompatibility was assessed on 16-HBE cell lines, measuring anti-inflammatory effects via IL-6 and IL-8 levels. Spray drying was optimized to produce microparticles using mannitol (MAN), leucine (LEU), and N-acetylcysteine (NAC). The nanoparticles had a size of 186 nm and a DL% of 2.9% for MePD. They showed good cytocompatibility, significantly reducing IL-6 and IL-8 levels. Spray drying yielded microparticles with a fine particle fraction (FPF) of 62.3% and a mass median aerodynamic diameter (MMAD) of 3.9 µm. Inclusion of LPHNPs@MePD (0.25% w/v) resulted in FPF and MMAD values of 56.7% and 4.4 µm. In conclusion, this study described the production of novel inhalable powders as carriers for MePD-loaded nanostructures with favorable physicochemical properties, cytocompatibility, and promising aerosol performance, indicating their potential as an effective inhalable therapy for lung inflammation with corticosteroids, especially for treating chronic diseases.

Inhalation Exposure to Cross-linked Polyacrylic Acid Induces Pulmonary Disorders.

Organic polymers, widely used in food, daily necessities, and medicines, include cross-linked polyacrylic acid (CL-PAA), which has been reported to induce severe lung disease. While previous studies mainly used intratracheal instillation, our research focused on inhalation exposure to corroborate these findings. We conducted 5-day (short-term) and 13-week (subchronic) inhalation exposure studies with CL-PAA. In the short-term study, male F344 rats inhaled CL-PAA at 0.2, 2.0, or 20mg/m³ for 6hours/day over 5 days. Rats were dissected 3 days and 1 month post-exposure. In the subchronic study, rats inhaled CL-PAA at 0.2 or 2.0mg/m³ for 6hours/day, 5 days/week for 13 weeks, with dissections from 3 days to 6 months post-exposure. To investigate the mechanism of pulmonary disorders, an additional short-term study with 20mg/m³ CL-PAA included intraperitoneal injections of the antioxidant N-acetylcysteine (NAC) (200mg/kg) with dissection the day after exposure. Short-term exposure led to concentration-dependent increases in neutrophil influx, cytokine-induced neutrophil chemoattractant (CINC), total protein, lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Histopathology showed concentration-dependent neutrophil infiltration. Subchronic exposure caused persistent increases in BALF total protein and lung HO-1, with ongoing neutrophil infiltration and fibrosis. NAC administration reduced neutrophils, total protein, LDH, and CINC in BALF, and HO-1 in lung tissue, improving histopathological findings. Inhalation of CL-PAA caused concentration-dependent lung inflammation and persistent fibrosis. The no observed adverse effect level (NOAEL) for chronic pulmonary disorders was 0.2mg/m³. Oxidative stress linked to CL-PAA-induced inflammation was mitigated by NAC administration.

N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) includes a range of neurodevelopmental disabilities characterized by social interaction deficits, communication impairments, and repetitive behaviors. Previous studies have shown that pro-inflammatory conditions play a key role in ASD. Despite this, how oxidative stress and inflammation may contribute to ASD-related behaviors is still poorly understood. Here, we reported that increased levels of molecules related to inflammation are present in the cerebellum and peripheral blood (PB) of mice lacking Shank3b, an established model of syndromic ASD. In parallel, immune dysfunction was documented in the bone marrow (BM) and spleens of mutant mice. N-acetylcysteine (NAC) treatment rescued inflammation in the cerebellum and PB and impaired the production of pro-inflammatory molecules in the BM and spleen. In addition, social impairment was counteracted in NAC-treated Shank3b-/- animals. Taken together, our results provide clear evidence of the key role of cerebellar oxidative stress and inflammation in the establishment of ASD-related behaviors. Furthermore, our findings underscore the importance of considering ASD as a systemic disorder.

AMTAC-19, a Spiro-Acridine Compound, Induces In Vitro Antitumor Effect via the ROS-ERK/JNK Signaling Pathway.

Colorectal cancer remains a significant cause of mortality worldwide. A spiro-acridine derivative, (E)-1'-((4-bromobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-19), showed significant cytotoxicity in HCT-116 colorectal carcinoma cells (half maximal inhibitory concentration, IC50 = 10.35 ± 1.66 µM) and antioxidant effects after 48 h of treatment. In this study, Molegro Virtual Docker v.6.0.1 software was used to investigate the interactions between AMTAC-19 and the Extracellular Signal-Regulated Kinase 1 (ERK1), c-Jun N-terminal Kinase 1 (JNK1), and p38 Mitogen-Activated Protein Kinase α (p38α MAPK). In vitro assays were conducted in HCT-116 cells to evaluate the effect of AMTAC-19 on the modulation of these proteins' activities using flow cytometry. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the presence or absence of ERK1/2, JNK, and p38 MAPK inhibitors was used to evaluate the involvement of these enzymes in AMTAC-19 cytotoxicity. ROS production was assessed using the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) assay at various incubation times (30 min, 1 h, 6 h, 12 h, and 24 h), and the MTT assay using N-acetyl-L-cysteine (NAC) was performed. In silico results indicated that AMTAC-19 interacts with ERK1, JNK1, and p38α MAPK. Additionally, AMTAC-19 activated ERK1/2 and JNK1 in HCT-116 cells, and its cytotoxicity was significantly reduced in the presence of ERK1/2 and JNK inhibitors. AMTAC-19 also induced a significant increase in ROS production (30 min and 1 h), while NAC pretreatment reduced its cytotoxicity. These findings support AMTAC-19's in vitro antitumor effect through ROS-dependent activation of ERK and JNK pathways.

The effects of antioxidant administration in the early stages of radiation-induced tumorigenesis.

ApcMin/+ mouse was a model mouse for human familial adenomatous polyposis, and irradiation at an early age increases tumors in the small and large intestine. To study the effects of antioxidant administration on tumor incidence after continuous whole-body exposure to gamma rays, ApcMin/+ mice were exposed to a medium-dose-rate, 200mGy/d, from postnatal Day 0 to 21 of age or a high-dose-rate of 0.65Gy/min (total dose 4.2Gy) on postnatal Day 7. The dams and pups were supplied with the N-acetylcysteine (NAC) in drinking water (7g/L), from gestation Day 15 until weaning (21days-old). A significant increase in the number of intestinal tumors were observed in ApcMin/+ mice irradiated with high dose-rate gamma rays as compared with the non-irradiated controls, but there was no significant difference in tumor counts between the non-irradiated controls and the medium-dose rate irradiation groups. NAC administration did not have any significant effect at least at this dose. These results suggest that the supplementation of anti-oxidant at the early stage of tumorigenesis does not suppress the formation of irradiation-induced small intestinal tumors.

Heat-inactivated Streptococcus pneumoniae augments circadian clock gene expression in zebrafish cells

The circadian clock is a cell-autonomous process that regulates daily internal rhythms by interacting with environmental signals. Reports across species show that infection can alter the expression of circadian genes; however, in teleosts, these effects are influenced by light exposure. Currently, no reports analyze the direct effects of bacterial exposure on the zebrafish clock. Using zebrafish Z3 cells, we demonstrate that exposure to heat-killed Streptococcus pneumoniae (HK-Spn) augments the expression of core repressive factors in a light- and time-dependent manner. In constant darkness, HK-Spn highly upregulated cry1a, per3, and per1b expression. In the presence of light, HK-Spn exposure rapidly and strongly upregulated per2 and cry1a, and this was proportionally increased with light intensity. The combinatorial effect of light and HK-Spn on per2 and cry1a was not duplicated with H2O2, a known byproduct of light exposure. However, the ROS inhibitor N-acetyl cysteine was sufficient to block HK-Spn augmentation of per2, cry1a, and per3. These findings demonstrate that exposure to an inactive bacteria influences the expression of zebrafish clock genes under different light conditions.

Acute Effect of Oral N-Acetylcysteine Supplementation on Fatigue Effect and Isometric Force Production in Physically Active People

The main objective of this study was to assess the ergogenic effect of N-acetylcysteine (NAC) on myotendinous isometric force production in physically active people after being subjected to a fatigue protocol. Twenty-three physically active people were randomly divided into the following two groups: NAC (n = 12; age = 26.8 ± 4.5 years, height = 173.1 ± 7.2 cm, and weight = 75.5 ± 7.5 kg), who received 2400 mg oral NAC, and control (n = 11; age = 23.4 ± 5.8 years, height = 175.9 ± 4.5 cm, and weight = 72.3 ± 9.9 kg), who received a placebo, for eight days. The isometric force production was assessed pre- and post-NAC supplementation during a maximal voluntary contraction test (MVC) and also during a fatigue protocol composed of seven sets of ten maximal isometric contraction repetitions of 5 s, with 5 s of rest between repetitions and 20 s between sets. No differences were observed between the groups in the force production values at any moment, and no side effects were found after NAC supplementation. After supplementation, a significant decrease in force was observed in both groups, but this significant loss of force started one set later in the NAC group compared to the control group (4th set vs. 5th set), which could be an ergogenic effect of the treatment. Therefore, oral daily supplementation with 2400 mg of NAC for eight days, could delay the decrease in force production during an isometric exercise protocol and without adverse side effects.

Antioxidant Therapies in the Treatment of Aminoglycoside-Induced Ototoxicity: A Meta-Analysis.

A feared complication of aminoglycoside treatment is ototoxicity, which is theorized to be attributed to the production of aminoglycoside-induced reactive oxygen species. Previous studies using animal models have suggested that numerous therapies targeting reducing oxidative stress may prevent ototoxicity from aminoglycosides. However, few clinical studies have been conducted on these antioxidants. This systematic review and meta-analysis examines the effectiveness of antioxidant therapies in the treatment of aminoglycoside-induced ototoxicity. PubMed, Embase, Web of Science, and ClinicalTrials.gov. A literature search was conducted in August 2024. This review sought randomized controlled trials to be conducted on humans to examining otologic outcomes in aminoglycoside-induced ototoxicity following administration of medications intended to reduce oxidative stress. A systematic review yielded 2037 results, of which seven studies met inclusion criteria. N-acetylcysteine (NAC) was investigated in four studies, aspirin in two studies, and vitamin E in one study. Six studies examined the benefit of antioxidant treatments for up to 8 weeks after administration while one study tested subjects' hearing after 1 year. In pooled analysis, two studies assessing NAC showed the greatest reduction in ototoxicity (RR 0.112, 95% CI, 0.032-0.395; p = 0.0007; I2 = 18%), followed by two studies examining aspirin (RR 0.229, 95% CI, 0.080-0.650; p = 0.0057; I2 = 0%). One study performed with vitamin E did not find a reduction in ototoxicity compared to the placebo (RR 0.841, 95% CI, 0.153-4.617; p = 0.8416). Multiple studies have shown that NAC and aspirin are effective in reducing ototoxicity from treatment with aminoglycosides. However, there is a lack of high-quality evidence. Additional studies should examine whether aspirin and N-acetylcysteine provide long-term benefit, and which of the other promising antioxidants translate from animal models. N/A Laryngoscope, 2024.

Towards the Development of Novel, Point-of-Care Assays for Monitoring Different Forms of Antioxidant Activity: The RoXstaTM System.

(1) Background: This study set out to develop a series of simple, novel, rapid methods for assessing different forms of antioxidant activity. (2) Methods: An ABTS platform was used to engineer: (i) an electrochemical post-activation assay to assess free radical scavenging activity; (ii) an electrochemical pre-activation strategy to assesses the suppression of free radical formation; (iii) a horseradish peroxidase-mediated oxidation system to monitor hydrogen peroxide scavenging activity and (iv) a cumene peroxide-hematin system to determine the ability of samples to scavenge the mixture of organic peroxides and peroxyl and alkoxyl radicals generated in the presence of these reagents. Each assay was assessed against a panel of candidate antioxidant compounds to determine their relative activities and specificities. In addition, human semen samples were analyzed to determine how the results of these antioxidant assays correlated with semen quality. (3) Results: All 4 assays revealed dose-dependent antioxidant activity on the part of vitamin C, N-acetyl cysteine, hypotaurine, BSA, melatonin, glutathione, resveratrol and epigallocatechin gallate. The other compounds tested either completely lacked antioxidant activity or were only active in one of the assays. Using unfractionated human semen as an exemplar of biological fluids rich in antioxidants, the outputs from the individual assays were found to reflect different aspects of semen quality. When the data from all 4 assays were combined, accurate predictions were generated reflecting the importance of oxidative stress in defining semen quality as reflected by sperm count, seminal lipid aldehyde content, sperm DNA damage and free radical generation by the sperm mitochondria. (4) Conclusions: The methodologies described in this paper constitute the basis for rapid, point-of-care assessments of oxidative stress.

Renoprotective Effects of Brown-Strain Flammulina velutipes Singer in Chronic Kidney Disease-Induced Mice Through Modulation of Oxidative Stress and Inflammation and Regulation of Renal Transporters.

Cisplatin, widely used in chemotherapy, acts through mechanisms such as oxidative stress to damage the DNA and cause the apoptosis of cancer cells. Although effective, cisplatin treatment is associated with considerable side effects including chronic kidney disease (CKD). Studies on brown-strain Flammulina velutipes Singer (FVB) have shown its significant antioxidant and immunomodulatory effects. High-performance liquid chromatography (HPLC) confirmed that the FVB extract contained gallic acid and quercetin. This study investigated whether FVB extract can improve and protect against cisplatin-induced CKD in mice. C57BL/6 mice were used as an animal model, and CKD was induced through intraperitoneal cisplatin injection. FVB was orally administered to the mice for 14 consecutive days. N-acetylcysteine (NAC) was administered in the positive control group. Organ pathology and serum biochemical analyses were conducted after the mice were sacrificed. Significant dose-dependent differences were discovered in body mass, kidney mass, histopathology, renal function, inflammatory factors, and antioxidant functions among the different groups. FVB extract reduced the severity of cisplatin-induced CKD in pathways related to inflammation, autophagy, apoptosis, fibrosis, oxidative stress, and organic ion transport proteins; FVB extract, thus, displays protective physiological activity in kidney cells. Additionally, orally administered high doses of the FVB extract resulted in significantly superior renal function, inflammatory factors, antioxidative activity, and fibrotic pathways. This study establishes a strategy for future clinical adjunctive therapy using edible-mushroom-derived FVB extract to protect kidney function.

The Protective Effects of Mito-TEMPO on Acetaminophen-induced Hepatotoxicity: A Systematic Review

Background: Acetaminophen overdose is a leading cause of acute liver failure glob-ally. Current treatment options, primarily N-acetylcysteine (NAC), have limitations. Mito-TEMPO (Mito-T), a mitochondria-targeted antioxidant, has shown potential in preclinical stud-ies. This systematic review evaluated the evidence for Mito-T's hepatoprotective effects against acetaminophen-induced liver injury. Methods: We conducted a comprehensive search of databases and grey literature following PRISMA guidelines. Studies published between 2000 and 2023 on Mito-T and acetaminophen-induced hepatotoxicity in animal models were included. Data on study characteristics, inter-ventions, outcomes, and risk of bias were extracted. Results: Six high-quality studies were included. Mito-T administration significantly reduced serum alanine transaminase (ALT) levels, a marker of liver injury, compared to controls. Mito-T also protects against hepatocellular necrosis, apoptosis, and mitochondrial dysfunction. These effects were likely mediated by Mito-T's ability to scavenge reactive oxygen and nitrogen spe-cies within mitochondria. Conclusion: This review provides strong evidence that Mito-T effectively protects against ac-etaminophen-induced liver injury in animal models. Mito-T’s mechanisms of action address a critical pathophysiological pathway in acetaminophen toxicity. While limitations, including the use of animal models and potential for publication bias, exist, the findings suggest Mito-T holds promise as a novel therapeutic option. Further studies are needed to assess Mito-T's safety, pharmacokinetics, and optimal dosing in humans. Clinical trials comparing Mito-T against NAC are warranted if toxicity profiles are favorable. Additionally, investigating Mito-T's po-tential in other diseases involving oxidative stress is crucial.

Changes in Resting-State Functional Connectivity and Cognitive-Affective Symptoms in Patients With Post-Concussion Syndrome Treated With N-Acetyl Cysteine.

Concussion accounts for more than 80% of people experiencing traumatic brain injury. Acute concussion is associated with characteristic cognitive and functional deficits that may persist for weeks to months. A subgroup of these patients (from 10% to 50%) have persistent symptoms referred to as chronic post-concussion syndrome (PCS). There are limited treatment options for these patients and the pathophysiology is poorly understood, though oxidative stress is thought to be a contributing factor. The purpose of this study was to evaluate whether an antioxidant, N-acetylcysteine (NAC), might be beneficial in patients with PCS. Outpatient medicine center. Fifty patients with chronic PCS for at least 3 months post injury. The patients with PCS were enrolled in this randomized unblinded clinical trial to receive the antioxidant NAC as a combination of daily oral and weekly intravenous infusions, or assigned to a waitlist control group where they would continue to receive standard of care. Resting-state functional connectivity (FC) magnetic resonance imaging (rsFC-MRI) was performed pre and post either NAC or the waitlist period along with cognitive, emotional, and sensory symptom assessments. The results demonstrated significant (P <.05) improvements in symptoms as determined by the Rivermead Post-Concussion Symptoms Questionnaire, Spielberger State-Trait Anxiety Inventory, and Profile of Mood Scale in the PCS group receiving NAC as compared to patients receiving ongoing standard care. Importantly, there were significant (P<.01) changes in FC in the NAC group, particularly in networks such as the default mode network, salience network, and executive control network. These changes in FC also correlated with improvements in symptoms. In patients with chronic PCS, NAC treatment was associated with significant changes in resting state FC and improvement in a variety of symptoms, particularly cognitive and affective symptoms.

The Effects of Antioxidant Supplementation on Soccer Performance and Recovery: A Critical Review of the Available Evidence.

Background Soccer is linked to an acute inflammatory response and the release of reactive oxygen species (ROS). Antioxidant supplements have shown promising effects in reducing muscle damage and oxidative stress and enhancing the recovery process after eccentric exercise. This critical review highlights the influence of antioxidant supplements on performance and recovery following soccer-related activity, training, or competition. Methods: English-language publications from the main databases that examine how antioxidant-based nutrition and supplements affect the recovery process before, during, and after soccer practice or competition were used. Results:Coenzyme Q10 (CoQ10), astaxanthin (Asx), red orange juice (ROJS), L-carnitine (LC), N-acetyl cysteine (NAC), beetroot (BET), turmeric root, and tangeretin reduce muscle damage (creatine kinase, myoglobin, cortisol, lactate dehudrogenase, muscle soreness). Tangeretin, docosahexaenoic acid (DHA), turmeric root, and aronia melanocarpa restrict inflammation (leukocytes, prostalagdin E2, C-reactive protein, IL-6 and 10). Q10, DHA, Asx, tangeretin, lippia citriodora, quercetin, allopurinol, turmeric root, ROJS, aronia melanocarpa, vitamins C-E, green tea (GTE), and sour tea (STE) reduce oxidative stress (malondialdehude, glutathione, total antioxidant capacity, superoxide dismutases, protein carbonyls, ascorbate, glutathione peroxidase, and paraoxonase 1). BET and NAC reinforce performance (endurance, jump, speed, strength). Conclusions: Further research is needed to determine the main mechanism and the acute and long-term impacts of antioxidant supplements in soccer.