Preparation and evaluation of inhalable S-allylmercapto-N-acetylcysteine and nintedanib co-loaded liposomes for pulmonary fibrosis.

Orally marketed products nintedanib (NDNB) and pirfenidone (PFD) for pulmonary fibrosis (PF) are administered in high doses and have been shown to have serious toxic and side effects. NDNB can cause the elevation of galectin-3, which activates the NF-κB signaling pathway and causes the inflammatory response. S-allylmercapto-N-acetylcysteine (ASSNAC) can alleviate the inflammation response by inhibiting the TLR-4/NF-κB signaling pathway. Therefore, we designed and prepared inhalable ASSNAC and NDNB co-loaded liposomes for the treatment of pulmonary fibrosis. The yellow, spheroidal co-loaded liposomes with a particle size of 98.32±1.98 nm and zeta potential of -22.5 ± 1.58 mV were produced. The aerodynamic fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of NDNB were >50 % (81.14 %±0.22 %) and <5 µm (1.79 µm±0.06 µm) in the nebulized liposome solution, respectively. The results showed that inhalation improved the lung deposition and retention times of both drugs. DSPE-PEG 2000 in the liposome formulation enhanced the mucus permeability and reduced phagocytic efflux mediated by macrophages. ASSNAC reduced the mRNA over-expressions of TLR-4, MyD88 and NF-κB caused by NDNB, which could reduce the NDNB's side effects. The Masson's trichrome staining of lung tissues and the levels of CAT, TGF-ß1, HYP, collagen III and mRNA expressions of Collagen I, Collagen III and α-SMA in lung tissues revealed that NDNB/Lip inhalation was more beneficial to alleviate fibrosis than oral NDNB. Although the dose of NDNB/Lip was 30 times lower than that in the oral group, the inhaled NDNB/Lip group had better or comparable anti-fibrotic effects to those in the oral group. According to the expressions of Collagen I, Collagen III and α-SMA in vivo and in vitro, the combination of ASSNAC and NDNB was more effective than the single drugs for pulmonary fibrosis. Therefore, this study provided a new scheme for the treatment of pulmonary fibrosis.

[Nephroprotective value of N-acetylcysteine for patients with concomitant trauma, as well as other aspects of the use of this drug in clinical practice].

An analysis and review of domestic and foreign literature on the role of N-acetylcysteine in the correction of oxidative stress, as well as the problem of oxidative stress, and protection against free radicals are presented in the article. The important role of N-acetylcysteine in replenishing the intracellular glutathione level, which is the main cell antioxidant, has been shown, as well as the potential use of N-acetylcysteine for various pathological conditions and diseases. The relevance of concomitant injury and renal dysfunction, and the experience of the clinical use of N-acetylcysteine as a nephroprotector in patients with concomitant injury in the clinic of the Department of Faculty and Endoscopic Surgery of KBSU named after Kh.M. Berbekov are also described. After reviewing the literature, based on the results of many experimental studies, we can conclude that this pharmacological substance is a very promising for replenishing the intracellular glutathione pool, and it becomes possible to include it in the combined therapy of a number of human diseases.

Evaluation of efficacy and safety of vitiligo treatment with micro-needling combined with N-Acetylcysteine and micro-needling alone: A double-blinded randomized controlled clinical trial.

INTRODUCTION: Vitiligo is a skin pigmentation disorder caused by the selective degradation of melanocytes. This study investigates the therapeutic effects of microneedling with and without N-acetylcysteine (NAC) in patients with persistent and limited vitiligo. METHOD: This research employed a clinical trial design with double-blind randomization. Individuals affected by vitiligo and seeking treatment at Rasool Akram Medical Complex were divided into two separate treatment groups. In the intervention group, 24 affected areas underwent meso-microneedling using 5% NAC ampoules over six sessions, in addition to the application of 4.7% NAC cream once daily on the specified area. Conversely, the control group, consisting of 22 lesions, underwent microneedling using distilled water during six sessions. The severity of lesions and the extent of repigmentation were gauged using the Modified VETI Score. Assessment of treatment efficacy was determined through both physician evaluations and patient feedback. RESULTS: Twenty patients with a mean age of 36.4 years were recruited. The mean percentage of lesions and their intensity were significantly improved 2 weeks after the third session and 1 month after the end of the treatment (p < 0.01). There was no statistically significant difference between the intervention and control groups. Gender, age, family history, duration of disease, duration of disease stability, and history of hypothyroidism had no statistically significant relationship with patients' treatment outcomes (p > 0.05). CONCLUSION: Microneedling with or without the application of NAC appears to be an effective treatment option for persistent vitiligo lesions. However, despite the higher improvement rate with the application of NAC, the difference was not significant.

Papel de N-acetilcisteína (NAC) en pacientes con tabaquismo / Role of N-acetylcysteine (NAC) in patients with smoking

Antecedentes y objetivo. El tabaquismo es el principal factor de riesgo de la enfermedad pulmonar obstructiva crónica (EPOC). N-acetilcisteína (NAC) es un agente mucolítico con propiedades antioxidantes y antiinflamatorias que ha demostrado ser eficaz en la reducción de la tasa de exacerbaciones y mejoría clínica de los pacientes con EPOC. El objetivo del trabajo es conocer la opinión de terapeutas expertos acerca del perfil o perfiles de los pacientes fumadores que pueden ser candidatos al uso de NAC. Métodos. Se efectuó una encuesta distribuida a las unidades de tabaquismo de España y una Reunión de Expertos en tabaquismo y EPOC, en la que los Expertos pudieron debatir abiertamente los tópicos seleccionados. Resultados. Los expertos reconocieron el papel del tabaquismo en la generación de estrés oxidativo y concordaron en emplear la terapia mucolítica/antioxidante para fumadores o exfumadores con síntomas respiratorios. Se debatió la necesidad de ampliar las indicaciones de esta terapia a otros perfiles de pacientes. Se señaló también el potencial efecto preventivo de la NAC sobre el daño pulmonar por su acción antioxidante, aunque se necesitaría más evidencia en este ámbito específico del tabaquismo. Se puso énfasis en diferenciar la dosis de NAC como mucolítico (600 mg/día)o antioxidante (1.200 mg/día). Conclusiones. Los expertos valoraron a NAC como un fármaco bien tolerado, de sencillo uso, con un conocido buen perfil de seguridad y un gran potencial para lograr los objetivos terapéuticos por su alta capacidad antioxidante. (AU)

Background and objective. The smoking habit is the main risk factor for chronic obstructive pulmonary disease (COPD). N-Acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties that has been demonstrated to be effective in the reduction of the rate of exacerbations and clinical improvement of patients with COPD. This study aims to know the opinion of the expert therapists on the profile(s) of the patients who smoke and who may be candidates for the use of NAC. Methods. A survey was performed, distributing it to the smoking units in Spain and to a Meeting of Experts on the smoking habit and COPD in which the Experts could openly debate on the selected topics. Results. The experts recognized the role of the smoking habit in the generation of oxidative stress and agreed to use the mucolytic/antioxidant treatment for smokers or ex-smokers with respiratory symptoms. The need to extend the indications of this therapy to other patient profiles was debated. The potential preventive effect of NAC on lung damage due to its antioxidant action was also pointed out, although more evidence in this special area of the smoking habit would be necessary. Emphasis was placed on differentiating the NAC dose as a mucolytic (600 mg/day) or as an antioxidant (1,200 mg/day). Conclusions. The experts evaluated NAC as a drug that is well-tolerated, easy-to-use, with a known good safety profile and having great potential to achieve the therapeutic objectives due to its high antioxidant capacity. (AU)

Is the combination of linagliptin and allopurinol better prophylaxis against post-contrast acute kidney injury? A multicenter prospective randomized controlled study.

BACKGROUND: Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD. METHODS: Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2nd received allopurinol, the 3rd group received linagliptin, and the 4th received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients. RESULTS: 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (p < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis. CONCLUSION: Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03470454.

Analysis of serum microRNA-122 in a randomized controlled trial of N-acetylcysteine for treatment of antituberculosis drug-induced liver injury.

AIM: Serum microRNA-122 (miR-122) is a novel biomarker for drug-induced liver injury, with good sensitivity in the early diagnosis of paracetamol-induced liver injury. We describe miR-122 concentrations in participants with antituberculosis drug-induced liver injury (AT-DILI). We explored the relationship between miR-122 and alanine aminotransferase (ALT) concentrations and the effect of N-acetylcysteine (NAC) on miR-122 concentrations. METHODS: We included participants from a randomized placebo-controlled trial of intravenous NAC in AT-DILI. ALT and miR-122 concentrations were quantified before and after infusion of NAC/placebo. We assessed correlations between ALT and miR-122 concentrations and described changes in ALT and miR-122 concentrations between sampling occasions. RESULTS: We included 45 participants; mean age (± standard deviation) 38 (±10) years, 58% female and 91% HIV positive. The median (interquartile range) time between pre- and post-infusion biomarker specimens was 68 h (47-77 h). The median pre-infusion ALT and miR-122 concentrations were 420 U/L (238-580) and 0.58 pM (0.18-1.47), respectively. Pre-infusion ALT and miR-122 concentrations were correlated (Spearman's ρ = .54, P = .0001). Median fold-changes in ALT and miR-122 concentrations between sampling were 0.56 (0.43-0.69) and 0.75 (0.23-1.53), respectively, and were similar in the NAC and placebo groups (P = .40 and P = .68 respectively). CONCLUSIONS: miR-122 concentrations in our participants with AT-DILI were considerably higher than previously reported in healthy volunteers and in patients on antituberculosis therapy without liver injury. We did not detect an effect of NAC on miR-122 concentrations. Further research is needed to determine the utility of miR-122 in the diagnosis and management of AT-DILI.

Evaluation the efficacy and safety of N-acetylcysteine inhalation spray in controlling the symptoms of patients with COVID-19: An open-label randomized controlled clinical trial.

The aim of this study was to evaluate the effect and safety of N-acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID-19). This randomized controlled clinical trial study was conducted on patients with COVID-19. Eligible patients (n = 250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 h, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment. The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs. 3.2%, p < 0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs. 7.8, p < 0.001), hemoglobin (12.3 vs. 13.3, p = 0.002), C-reactive protein (CRP: 6 vs. 11.5, p < 0.0001) and aspartate aminotransferase (AST: 32 vs. 25.5, p < 0.0001). No differences were seen for hospital length of stay (11.98 ± 3.61 vs. 11.81 ± 3.52, p = 0.814) or the requirement for intensive care unit (ICU) admission (7.2% vs. 11.2%, p = 0.274). NAC was beneficial in reducing the mortality rate in patients with COVID-19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for Severe Acute Respiratory Syndrome Coronavirus-2 is limited and further research is required.

Phase I study of the pharmacokinetics and safety of single and multiple doses of intravenous N-acetylcysteine in healthy Chinese subjects.

OBJECTIVE: The aim of the study was to determine the pharmacokinetics (PK) and safety of single and repeat doses of intravenous (IV) N-acetylcysteine (NAC) in Chinese subjects. PATIENTS AND METHODS: A total of 24 healthy male and female Chinese subjects aged 19-40 years were enrolled in this open-label phase I study. All subjects received a single dose of NAC 600 mg IV on day 1 and, after a 3-day washout, received repeat doses of NAC 600 mg IV (twice daily on days 4 and 5 and once on day 6). RESULTS: Following a single dose, plasma NAC concentrations peaked rapidly, starting to fall at the end of the 5-minute infusion in a multiphasic manner. Mean Cmax was 83.30 µg/mL (CV% 30.7%), median Tmax was 0.083 h (range 0.08-0.25 h), and mean AUC(0-12 h) was 81.87 h*µg/mL (CV 14.0%). Following repeat dosing, Cmax was approximately 20% higher than after a single dose, with similar Tmax. Total exposure AUC(0-12) was 13% higher at steady state than after single dosing. The accumulation ratio was approximately 1.13, indicating only a slight accumulation with multiple dosing. NAC was eliminated with T1/2 of approximately 8 hours. Around 15% of the total NAC dose was excreted in the urine in the 32 hours post-dose, keeping with extensive NAC metabolism and transformation. Renal clearance of NAC was 995.2 mL/h (CV 50.2%). IV NAC was well tolerated after both single and multiple dosing. CONCLUSIONS: This is the first robust study evaluating the PK and safety of IV NAC 600 mg in Chinese subjects and provides important data if this agent is to be used IV as a mucolytic in this population.

Prospective cohort study to evaluate premedication with simethicone and n-acetilcysteine for upper diagnostic gastrointestinal endoscopy

Introduction: The use of premedication for upper gastrointestinal endoscopy (UGE) is not widely established in western countries. The primary aim of the study was to compare gastric visibility according to the total visibility score (TVS). The secondary aim was to assess complications, diagnostic yield, endoscopic procedure time, sedation dose and patient satisfaction. Methods: A single center prospective cohort study was performed of consecutive adults undergoing an UGE in the afternoon working shift. After completing enrolment in the control group, patients were administered 200 mg simethicone and 500 mg N-acetylcysteine diluted in 100 ml of water >15 minutes before the procedure. All procedures were recorded and a single, blinded endoscopist evaluated the TVS after recruitment of both cohorts. Patient satisfaction was evaluated using the Spanish translation of the American Society of Gastrointestinal Endoscopy satisfaction questionnaire. Results: 205 patients were included in the study, 103 females (50.2%) with a median age of 54.8-years (IQR: 41.2-65.2). 104 were enrolled to the control group and 101 to the intervention group. Patients receiving premedication presented a higher rate of adequate (74.3% vs 45.2; difference 95% CI: 16,3-41,9%, p<0.001) and excellent gastric visibility (23.8% vs 7.7%; difference 95% CI: 6,3-25,8%, p=0.002). Propofol dose was similar, although the median procedure time was lower in the group of no intervention [5 (IQR: 4-7) vs 6 minutes (IQR: 5-7); p=0.03]. Procedure related adverse events were similar, except that patient without premedication experienced more nausea episodes. Major and minor endoscopic findings and the satisfaction questionnaire showed no differences between both groups. Conclusion: Patients receiving premedication with simethicone and N-acetylcysteine had a better gastric visibility score, without any increase in adverse events or affecting the patients’ satisfaction (AU)

Indicación de N-acetilcisteína en distintas formas de toxicidad por paracetamol / Indication of n-acetylcysteine in differents forms of paracetamol toxicity

Introducción: la hepatotoxicidad por paracetamol está relacionada con la formación del metabolito N-acetil-parabenzoquinoneimina (NAPQI) y su falta de detoxificación a través del glutatión, cuyas reservas se deplecionan en el contexto de una sobredosis. La administración de N-acetilcisteína (NAC) como sustancia dadora de grupos tioles (-SH) contribuye a la prevención del daño hepático que puede desarrollarse con dosis terapéuticas o tóxicas. Métodos: se comentan 5 casos de exposición a paracetamol en los cuales se administró NAC por alteración de la función hepática. La gravedad de los cuadros varió en función de las dosis y del tiempo de latencia hasta la consulta. Resultados: cuatro pacientes ingirieron una única dosis tóxica y una paciente recibió la dosis diaria máxima de paracetamol de 4000 mg/día durante 5 días. La paciente que consultó dentro de las 4 horas posteriores a la ingesta no presentó elevación de transaminasas. Todas las pacientes recibieron NAC y sus valores de enzimas hepáticas se normalizaron al momento del alta. Conclusión: la administración temprana de NAC puede ser útil para prevenir daño hepático tanto en ingestas de dosis tóxicas, como en casos de utilización de dosis terapéuticas máximas durante varios días. (AU)

Introduction: paracetamol hepatotoxicity is related to the formation of the metabolite N-acetyl-parabenzoquinoneimine (NAPQI) and its lack of detoxification through glutathione, whose reserves are depleted in paracetamol overdose. The administration of N-acetylcysteine (NAC) as a donor of sulfhydryl groups (-SH) can prevent liver damage that could even occur with therapeutic or toxic doses. Methods: 5 cases of exposure to paracetamol are discussed, in which NAC was administered due to impaired liver function. These manifestations presented different severity depending on the drug doses and the time until medical consultation. Results: four patients ingested single toxic doses and one patient received the maximum daily dose of paracetamol of 4000 mg/day for 5 days. The patient who consulted within 4 hours after ingestion did not present elevation of transaminases. All patients received NAC, with normal liver enzymes at discharge. Conclusion: the early administration of NAC may be useful to prevent liver damage both in toxic dose intakes and in cases of use of maximum therapeutic doses for several days. (AU)

Estudio multicéntrico sobre el tratamiento con N-acetilcisteína como antídoto en la intoxicación por paracetamol / N-acetylcysteine as an antidote for paracetamol poisoning: a multicenter study

Objetivo. Conocer los aspectos clínicos relacionados con el tratamiento del antídoto N-acetilcisteína (NAC) en las intoxicaciones por paracetamol. Método. Estudio observacional y retrospectivo de los pacientes atendidos por intoxicación por paracetamol en cuatro servicios de urgencias durante 3 años (2017-2019). Se analizan variables epidemiológicas, clínicas y asistenciales, así como la idoneidad y seguridad en el empleo del tratamiento antidótico. Resultados. Se incluyeron 332 intoxicaciones: 260 casos (78%) tenían más de 16 años y 242 (73%) fueron mujeres. Doscientos sesenta y ocho intoxicaciones (81%) fueron de causa voluntaria y la semivida de eliminación se determinó en 20 ocasiones (6%). La descontaminación digestiva se indicó de forma incorrecta en 39 ocasiones (28%). Se inició tratamiento con antídoto en 195 casos (58,7%). En 282 casos (85%) no hubo ninguna clínica de gravedad. La correlación entre la dosis referida ingerida y la paracetamolemia en los casos de ingesta voluntaria (R2 = 0,23) fue más fuerte que en los casos de ingesta accidental (R2 = 0,007). Existieron diferencias estadísticamente significativas al relacionar los criterios de gravedad con la dosis referida ajustada al peso (p = 0,001) y el intervalo desde la ingesta y la primera asistencia médica (p = 0,008). Conclusiones. Existe variabilidad en aspectos fundamentales del tratamiento antidótico en las intoxicaciones por paracetamol, a pesar de estar claramente protocolizado su manejo.

Objective. To identify the most common problems related to use of N-acetylcysteine to reverse the toxic effects of paracetamol poisoning. Methods. Retrospective descriptive observational study of clinical records for patients treated for paracetamol poisoning in 4 emergency departments during 3 years (2017-2019). We analyzed epidemiologic, clinical, and care variables, especially those related to the suitability and safety of using N-acetylcysteine as an antidote. Results. We included 332 cases of poisoning of 260 patients (78%) were over the age of 16 years, and 242 (73%) were female. Two hundred sixty-eight poisonings (81%) were the result of voluntary intake. The elimination half-life was determined in 20 cases (6%). Gastrointestinal decontamination was incorrectly prescribed on 39 occasions (28%). Treatment with the antidote was begun in 195 cases (58.7%). No serious clinical signs or symptoms were present in 282 cases (85%). The correlation of paracetamol levels in urine was stronger with the amount of drug ingested voluntarily (R2 = 0.23) than with accidental intake (R2 = 0.007). Predefined severity criteria were significantly related to reported dose ingested per body weight (P = .001) and the interval between intake and first medical assistance (P = .008). Conclusions. Even though clear protocols are available to guide the use of antidote treatment in cases of paracetamol poisoning, variability in fundamental aspects of management is excessive.

Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19.

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic and anti-inflammatory effect of BromAc® in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. METHOD: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine analysis using Luminex kit was performed. RESULTS: BromAc® displayed a robust mucolytic effect in a dose dependent manner on COVID-19 sputum ex vivo. BromAc® showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1Ra and total reduction for IL-9 compared to NAC alone and control. BromAc® acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250 µg. CONCLUSION: These results indicate robust mucolytic and anti-inflammatory effect of BromAc® ex vivo in tracheal aspirates from critically ill COVID-19 patients, indicating its potential to be further assessed as pharmacological treatment for COVID-19.

Sensitivity of dose-estimations for acute acetaminophen overdose in predicting hepatotoxicity risk using the Rumack-Matthew Nomogram.

Timely assessment of acetaminophen concentration in overdose situations is not always available in resource-poor settings. The 150 mg/kg dose-estimate for acetaminophen is widely considered as criterion for acetaminophen overdose. Its sensitivity and specificity when compared to the 150 mg/L treatment line on the Rumack-Matthew Nomogram (150-treatment line) has rarely been evaluated. This is a retrospective chart review of acute acetaminophen overdose patients. We evaluated the sensitivity and specificity of the 150, 200 mg/kg and 8- and 10-g dose-estimates by plotting the serum acetaminophen levels and using 150-treatment line on the Nomogram as the treatment cut-off. A comparison of medical care costs was performed. We enrolled 784 cases for analysis. Median (IQR) age was 23 (20-28) years (81.9% female). There were 545 cases (69.5%) where the estimated ingested acetaminophen dose were ≥150 mg/kg and 406 cases (51.8%) with concentrations ≥150-treatment line. Hepatotoxicity and acute liver injury (ALI) occurred in 7.3% and 23.9%, respectively. The sensitivity and specificity of 150 mg/kg dose-estimate for the 150-treatment line were 92.6% (95% CI 89.6, 94.8) and 55.3% (95% CI 50.3, 60.2). Among patients with dose-estimate below150 mg/kg, none developed hepatotoxicity and 17 (7.1%) develop ALI. The administration of activated charcoal significantly decreased the risk of being above the 150-treatment line by half. In resource-poor setings, the use of 150 mg/kg dose-estimate as a stand-alone criteria for initiation of N-acetylcysteine therapy is satisfactory, especially when combined with decontamination with activated charcoal and follow up of aminotransferase at 24 h.

The role of topical N-acetylcysteine in ocular therapeutics.

N-acetylcysteine (NAC) was first discovered as a mucolytic agent in 1960. We investigate the role of topical NAC in ocular therapeutics, including its mechanism of action, current applications, and adverse effects. A systematic search of peer-reviewed articles identified 106 references including in vitro, in vivo and clinical studies on the use of NAC in the treatment of ocular diseases. NAC can be synthetically manufactured, and its mechanisms of action include mucolysis, scavenging hydroxyl radicals, and modulation of inflammatory cascades. These unique properties contribute to the diverse applications of NAC, including its steroid-sparing potential. NAC has been used topically in the treatment of corneal wounds, chemical injuries, keratitis, dry eye disease and meibomian gland dysfunction. The clinical benefits of NAC are evident over a wide range of concentrations, the most common being 5-10% topical NAC applied four times daily. Adverse effects such as corneal necrosis are rare, but have been reported with higher doses. NAC also has potential applications in laser epithelial keratomileusis, diabetic eye disease, retinitis pigmentosa, senile nuclear cataracts, macular degeneration, and cigarette smoke-induced corneal damage. Recently, chitosan-NAC has been used as a nanocarrier for the topical administration of medications to the ocular surface. Owing to its potent antioxidant, anti-inflammatory and mucolytic properties, topical NAC has had extensive use in the treatment of ocular pathology.

Aflatoxin B1 induces microglia cells apoptosis mediated by oxidative stress through NF-κB signaling pathway in mice spinal cords.

Many studies have shown that aflatoxin B1 (AFB1) can cause cytotoxicity in numerous cells and organs induced by oxidative stress. However, the toxic effects and related mechanism of AFB1 on the microglia cells in the spinal cords have not been studied yet. Our results showed that AFB1 significantly reduced the number of microglia cells, increased the oxidants (malonaldehyde and hydrogen peroxide) but decreased the anti-oxidants (superoxide dismutase and total antioxidant capacity) in a dose dependent manner in mice spinal cords. In addition, AFB1 significantly increased the oxidative stress, promoted apoptosis and cell cycle arrest in G2-M phase, and activated NF-κB phosphorylation in BV2 microglia cells. However, the addition of active oxygen scavenger N-acetylcysteine can significantly reduce the ROS production, improve cell cycle arrest, reduce apoptosis, and the expression of phosphorylated NF-κB in BV2 microglia cells. These results indicate that AFB1 induces microglia cells apoptosis through oxidative stress by activating NF-κB signaling pathway.

Physiological and performance effects of dietary nitrate and N-acetylcysteine supplementation during prolonged heavy-intensity cycling.

The purpose of this study was to investigate effects of concurrent and independent administration of dietary nitrate (NO3-), administered as NO3--rich beetroot juice (BR; ~12.4 mmol of NO3-), and N-acetylcysteine (NAC; 70 mg·kg-1) on physiological responses during prolonged exercise and subsequent high-intensity exercise tolerance. Sixteen recreationally active males supplemented with NO3--depleted beetroot juice (PL) or BR for 6 days and ingested an acute dose of NAC or maltodextrin (MAL) 1 h prior to performing 1 h of heavy-intensity cycling exercise immediately followed by a severe-intensity time-to-exhaustion (TTE) test in four conditions: 1) PL+MAL, 2) PL+NAC, 3) BR+MAL and 4) BR+NAC. Pre-exercise plasma [NO3-] and nitrite ([NO2-]) were elevated following BR+NAC  and BR+MAL (both P < 0.01) compared with PL+NAC and PL+MAL; plasma [cysteine] was increased in PL+NAC  and BR+NAC (both P < 0.01) compared to PL+MAL. Muscle excitability declined over time during the prolonged cycling bout in all conditions  but was better preserved in PL+NAC  compared to BR+NAC (P < 0.01) and PL+MAL (P < 0.05). There was no effect of supplementation on subsequent TTE . These findings indicate that co-ingestion of BR and NAC does not appreciably alter physiological responses during prolonged heavy-intensity cycling or enhance subsequent exercise tolerance.

Can paricalcitol increase the effectiveness of n-acetylcysteine in contrast induced acute kidney prophylaxis in rats? A biochemical and histopathological study / ¿Puede el paricalcitol aumentar la eficacia de la n-acetilcisteína en la profilaxis renal aguda inducida por contraste en ratas? Un estudio bioquímico e histopatológico

SUMMARY: N-Acetylcysteine (NAC) is used for contrast induced acut kidney injury (CI-AKI) prophylaxis because of its antioxidant effects. Paricalcitol, which has reno-protective effects, is likely to provide a more effective prophylaxis when added to NAC treatment. The study was designed based on this hypothesis. The study was organised to include 4 groups each consisting of 7 rats. Group 1 was the control group, and Group 2 included rats with CI-AKI. Rats in Group 3 were administered NAC at a dose of 100 mg/kg via oral gavage once a day for 5 days. Rats in group 4 were administered paricalcitol at a dose of 0.4 mcg/kg once a day for 5 days in addition to NAC. CI-AKI was induced after the treatments in both groups. The study was terminated on the sixth day. Samples were collected from the rats' sera and kidney tissues to study oxidant and antioxidant parameters; kidney function tests were also studied. There were significant differences between the contrast nephropathy group (Group 2) and NAC and NAC+paricalcitol groups with respect to serum urea and creatinine levels. When the same groups were compared regarding oxidant (TOS-MDA) and antioxidant (TAC-Paraoxonase) parameters, we observed that the oxidant parameters increased in serum and kidney tissue samples with NAC use, and that effect was strengthened by the addition of paricalcitol to NAC treatment. However, despite increased antioxidant effectiveness, we observed no decrease in urea and creatinine levels when paricalcitol was added for CI-AKI in rats. There was no significant difference between Group 3 and Group 4. Paricalcitol provides a more potent antioxidant effect in both serum and kidney tissue samples when added to NAC treatment in rats with CI-AKI. Despite increased antioxidant parameters, however, paricalcitol does not provide a significant decrease in urea and creatinine levels.

RESUMEN: Debido a sus efectos atioxidantes la N- acetilcisteína (NAC) se usa para la profilaxis de la lesión renal aguda inducida por contraste (CI-AKI). Es probable que el paricalcitol, que tiene efectos renoprotectores, proporcione una profilaxis más eficaz cuando se agrega al tratamiento con NAC. En base a esta hipótesis el estudio fue diseñado para incluir cuatro grupos cada uno compuesto por siete ratas. El grupo 1 fue el grupo control y el grupo 2 incluyó ratas con CI-AKI. A las ratas del Grupo 3 se les administró NAC con una dosis de 100 mg/kg por sonda oral una vez al día, durante 5 días. A las ratas del grupo 4 se les administró paricalcitol a una dosis de 0,4 mcg/kg una vez al día durante 5 días, además de NAC. Se indujo CI-AKI después de los tratamientos en ambos grupos. El estudio finalizó el sexto día. Se recolectaron muestras de suero y tejidos renales de ratas para estudiar los parámetros oxidantes y antioxidantes; También se estudiaron las pruebas de función renal. Hubo diferencias significativas entre el grupo de nefropatía por contraste (Grupo 2) y los grupos NAC y NAC+paricalcitol con respecto a los niveles séricos de urea y creatinina. Cuando se compararon los mismos grupos con respecto a los parámetros oxidantes (TOS-MDA) y antioxidantes (TAC-Paraoxonase), observamos que los parámetros oxidantes aumentaron en muestras de suero y tejido renal con el uso de NAC, y ese efecto se vio reforzado por la adición de paricalcitol a tratamiento NAC. Sin embargo, a pesar de una mayor eficacia antioxidante, no observamos una disminución en los niveles de urea y creatinina cuando se agregó paricalcitol para CI-AKI en ratas. No hubo diferencias significativas entre el Grupo 3 y el Grupo 4. El paricalcitol proporciona un efecto antioxidante más potente tanto en muestras de suero como de tejido renal cuando se agrega al tratamiento con NAC en ratas con CI-AKI. Sin embargo, a pesar del aumento de los parámetros antioxidantes, el paricalcitol no proporciona una disminución sig- nificativa en los niveles de urea y creatinina.