Combination Of N-acetylcysteine Research Articles

Effects of concurrent training and N-acetylcysteine supplementation on cardiac remodeling and oxidative stress in middle-aged spontaneously hypertensive rats

BackgroundThis study evaluated the effects of concurrent isolated training (T) or training combined with the antioxidant N-acetylcysteine (NAC) on cardiac remodeling and oxidative stress in spontaneously hypertensive rats (SHR).MethodsSix-month-old male SHR were divided into sedentary (S, n = 12), concurrent training (T, n = 13), sedentary supplemented with NAC (SNAC, n = 13), and concurrent training with NAC supplementation (TNAC, n = 14) groups. T and TNAC rats were trained three times a week on a treadmill and ladder; NAC supplemented groups received 120 mg/kg/day NAC in rat chow for eight weeks. Myocardial antioxidant enzyme activity and lipid hydroperoxide concentration were assessed by spectrophotometry. Gene expression of NADPH oxidase subunits Nox2, Nox4, p22 phox, and p47 phox was evaluated by real time RT-PCR. Statistical analysis was performed using ANOVA and Bonferroni or Kruskal–Wallis and Dunn.ResultsEchocardiogram showed concentric remodeling in TNAC, characterized by increased relative wall thickness (S 0.40 ± 0.04; T 0.39 ± 0.03; SNAC 0.40 ± 0.04; TNAC 0.43 ± 0.04 *; * p < 0.05 vs T and SNAC) and diastolic posterior wall thickness (S 1.50 ± 0.12; T 1.52 ± 0.10; SNAC 1.56 ± 0.12; TNAC 1.62 ± 0.14 * mm; * p < 0.05 vs T), with improved contractile function (posterior wall shortening velocity: S 39.4 ± 5.01; T 36.4 ± 2.96; SNAC 39.7 ± 3.44; TNAC 41.6 ± 3.57 * mm/s; * p < 0.05 vs T). Myocardial lipid hydroperoxide concentration was lower in NAC treated groups (S 210 ± 48; T 182 ± 43; SNAC 159 ± 33 *; TNAC 110 ± 23 *# nmol/g tissue; * p < 0.05 vs S, #p < 0.05 vs T and SNAC). Nox 2 and p22 phox expression was higher and p47 phox lower in T than S [S 1.37 (0.66–1.66); T 0.78 (0.61–1.04) *; SNAC 1.07 (1.01–1.38); TNAC 1.06 (1.01–1.15) arbitrary units; * p < 0.05 vs S]. NADPH oxidase subunits did not differ between TNAC, SNAC, and S groups.ConclusionN-acetylcysteine supplementation alone reduces oxidative stress in untreated spontaneously hypertensive rats. The combination of N-acetylcysteine and concurrent exercise further decreases oxidative stress. However, the lower oxidative stress does not translate into improved cardiac remodeling and function in untreated spontaneously hypertensive rats.

Use of N-acetylcysteine plus simethicone to improve mucosal visibility in upper digestive endoscopy via systematic alphanumeric-coded endoscopy: a randomized, double-blind controlled trial.

The use of antifoaming and mucolytic agents prior to upper gastrointestinal (GI) endoscopy and a thorough systematic review are essential to optimize lesion detection. This study evaluated the effect of simethicone and N-acetylcysteine on the adequate mucosal visibility (AMV) of the upper GI tract by an innovative systematic method. This randomized, double-blind controlled trial included consecutive patients who underwent diagnostic upper GI endoscopy for screening for early neoplasms between August 2019 and December 2019. The upper GI tract was systematically assessed by systematic alphanumeric-coded endoscopy. Patients were divided into 4 groups: 1) water; 2) only simethicone; 3) N-acetylcysteine + simethicone; and 4) only N-acetylcysteine. The following parameters were assessed in each group: age, sex, body mass index, level of adequate mucosal visibility, and side-effects. A total of 4564 images from upper GI areas were obtained for evaluation. The mean AMV in the 4 groups was 93.98±7.36%. The N-acetylcysteine + simethicone group had a higher cleaning percentage compared with the other groups (P=0.001). There was no significant difference among the remaining groups, but several areas had better cleaning when a mucolytic or antifoam alone was used. No side-effects were found in any group. The combination of N-acetylcysteine plus simethicone optimizes the visibility of the mucosa of the upper GI tract, which could potentially increase diagnostic yield.

Combination of N-acetyl Cysteine and Thymoquinone Alleviates Hepatocellular Toxicities by Radiation and CCl4 Intoxication in SD Rats

Combination of N-acetyl Cysteine and Thymoquinone Alleviates Hepatocellular Toxicities by Radiation and CCl4 Intoxication in SD Rats

P1 | In vitro effect of N‐acetylcysteine in combination with doxycycline on biofilm formation capacity of Staphylococcus aureus and Escherichia coli

Journal of Veterinary Pharmacology and TherapeuticsVolume 46, Issue S1 p. 85-85 POSTER PRESENTATIONS P1 | In vitro effect of N-acetylcysteine in combination with doxycycline on biofilm formation capacity of Staphylococcus aureus and Escherichia coli First published: 11 June 2023 https://doi.org/10.1111/jvp.13280Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume46, IssueS1Special Issue: 15th International Congress of the European Association for Veterinary Pharmacology and Toxicology held Bruges, Belgium, July 2–5, 2023June 2023Pages 85-85 RelatedInformation

Efficacy of dexamethasone and N-acetylcysteine combination in preventing post-embolization syndrome after transarterial chemoembolization in hepatocellular carcinoma

Conventional transarterial chemoembolization (cTACE) is the current standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Post-embolization syndrome (PES) is complex clinical syndrome that presents as fever, abdominal pain, nausea, and vomiting. Either dexamethasone (DEXA) or N-acetylcysteine (NAC) is used to prevent PES; however, the synergistic effect of their combined therapy for preventing PES and liver decompensation has not been determined. To evaluate the efficacy of DEXA and NAC combination in preventing PES and liver decompensation after cTACE. Patients with Barcelona Clinic Liver Cancer stage A or B HCC who were scheduled for TACE were prospectively enrolled. All patients were randomly stratified to receive NAC and DEXA or placebo. The dual therapy (NAC + DEXA) group received intravenous administration of 10 mg DEXA every 12 h, NAC 24 h prior to cTACE (150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h), and a continuous infusion of 6.25 mg/h NAC plus 4 mg DEXA every 12 h for 48 h after cTACE. The placebo group received an infusion of 5% glucose solution until 48 h after procedure. PES was defined by South West Oncology Group toxicity code grading of more than 2 that was calculated using incidence of fever, nausea, vomiting, and pain. One-hundred patients were enrolled with 50 patients in each group. Incidence of PES was significantly lower in the NAC + DEXA group compared with in the placebo group (6% vs 80%; P < 0.001). Multivariate analysis showed that the dual treatment is a protective strategic therapy against PES development [odds ratio (OR) = 0.04; 95% confidence interval (CI): 0.01-0.20; P < 0.001). Seven (14%) patients in the placebo group, but none in the NAC + DEXA group, developed post-TACE liver decompensation. A dynamic change in Albumin-Bilirubin score of more than 0.5 point was found to be a risk factor for post-TACE liver decompensation (OR = 42.77; 95%CI: 1.01-1810; P = 0.049). Intravenous NAC + DEXA administration ameliorated the occurrence of PES event after cTACE in patients with intermediate-stage HCC.

Pharmaceutical Systems as a Strategy to Enhance the Stability of Oxytetracycline Hydrochloride Polymorphs in Solution

In order to improve the stability of oxytetracycline hydrochloride, a polymorphic antibiotic set of novel binary systems were developed using β-cyclodextrin and amino acids with different acid-basic characteristics as ligands. The formation constants for each system containing β-cyclodextrin, L-aspartic acid, histidine and N-acetylcysteine were determined by Scott's method and statistical studies. The structure of the binary systems with β-cyclodextrin and N-acetylcysteine was elucidated by NMR experiments. The effect β-cyclodextrin and N-acetylcysteine on the polymorph's chemical stability in aqueous and phosphate buffered saline solutions at 25 °C was monitored by an optimized and validated high-performance liquid chromatography method. The combination of N-acetylcysteine with the three polymorphs and the β-cyclodextrin system obtained with the form III demonstrated a reduction in the degradation rate of oxytetracycline hydrochloride in the aqueous solution when compared to each free form, with an increase of 20 h in the half time. It evidences that the use of amino acids as ligands constitutes an interesting alternative for pharmaceutical areas. In conclusion, based on the results obtained, these pharmaceutical systems could be candidates for the development of a pharmaceutical formulation for the administration of the drug through reconstituted solutions using the binary system as a promising tool for improving the stability of oxytetracycline hydrochloride polymorphs in solution.

Kinesin spindle protein inhibitor exacerbates cisplatin-induced hair cell damage

There is emerging evidence indicating that Kinesin family, plays vital roles in influencing the growth of axons, interference with the progression of tumor. However, the function of Kinesin member in the auditory organs remains unknown. SB743921, a kinesin spindle protein (KSP) inhibitor, was applied in mouse organ of Corti and House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line to examine the role of KSP in auditory system with and without cisplatin damage. Cell Counting Kit-8 (CCK-8) and Lactase dehydrogenase (LDH) release assay were conducted to evaluate cell activity and toxicity. Pretreatment with SB743921 increased the sensitivity of HEI-OC1 cells to cisplatin ototoxicity through promoting cell apoptosis and deteriorating superoxide generation mediated damage from cisplatin. SB743921 also enhanced cisplatin induced hair cell damage in explants of mouse cochleae in vitro. Furthermore, the combined N-acetylcysteine (NAC) treatment with cisplatin or with cisplatin and SB743921 both completely rescued the reduced number of hair cells impaired by cisplatin, confirming the strengthening function of superoxide accumulation by SB743921 after cisplatin treatment. Inhibition of kinesin spindle protein enhanced the susceptibility of hair cells to cisplatin induced damage in mouse cochlear explants and HEI-OC1 cells, indicating that kinesin spindle protein might be an unprecedented target to weaken the ototoxicity of platinum medicaments.

Effect of tiotropium bromide, N-acetylcysteine and respiratory training on pulmonary function, activity tolerance and quality of life of patients with chronic obstructive pulmonary disease

Purpose: To investigate the effect of application of tiotropium bromide and N- acetylcysteine in combination with respiratory training on the treatment of patients with chronic obstructive pulmonary disease (COPD), and the effect of the combined treatment on pulmonary function, tolerance of physical activity, and quality of life.Methods: One hundred COPD patients admitted to The First People’s Hospital of Guiyang (February 2019 - March 2021) were randomly and equally assigned to groups X and Y. Patients in Y were given tiotropium bromide in combination with N-acetylcysteine, while group X was treated with respiratory training, in addition to the treatment regimen in Y. Treatment efficacy, incidence of adverse reactions, pulmonary function indices, activity tolerance, quality of life (QLI) score, activities of daily living (ADL) score, and incidence of COPD at 2 weeks, 1 month and 2 months after treatment were determined, and compared between the two groups.Results: Relative to group Y, group X had significantly higher treatment efficacy, QLI score and ADL score (p &lt; 0.05). Furthermore, group X also had better pulmonary function indices and activity tolerance, lower incidence of adverse reactions, and lower COPD incidence at 2 weeks, 1 month and 2 months after treatment (p &lt; 0.05).Conclusion: Tiotropium bromide and N-acetylcysteine in combination with respiratory training enhanced therapeutic effect, pulmonary function, activity tolerance and quality of life of COPD patients.

Effects of Metformin and N-Acetylcysteine on Dyslipidemia in Streptozotocin-Induced Diabetic Rats

Background: Diabetes is a chronic health issue globally that has a high incidence. Aim: To see the effects of metformin and N-acetylcysteine on dyslipidemia in streptozotocin-induced diabetic rats. Study Design: Randomized controlled trial. Methodology: A total of 25 rats were divided into 05 equal groups. Diabetes was induced into rats by streptozotocin (35 mg/kg) single doze (i.p). Rats having blood sugar &gt;300 mg/dl after 48hrs were considered as diabetic. Negative and positive control groups were fed on standard diet. Treatment groups were given Metformin, N-acetylcysteine and combination of Metformin and N-acetylcysteine respectively for 4 weeks. Groups were compared for lipid profile thus efficacy of treatment given was evaluated. SPSS 25.0 was used to analyze the whole data. The difference between all the groups was analyzed using One-Way Analysis of Variance (ANOVA). Results: There was significant improvement in a treatment group that received both Metformin plus N-acetylcysteine while other treatment groups had little improvement. Conclusion: It was concluded that dyslipidemia was significantly reduced by use of N-acetylcysteine in combination with metformin among diabetic rats. Keywords: Diabetes Mellitus, Dyslipidemia, Metformin, N-acetylcysteine and Streptozotocin.

Simethicone and N-acetyl cysteine combination as premedication before esophagogastroduodenoscopy: Double-blind randomized controlled trial.

Background and study aims Esophagogastroduodenoscopy (EGD), the most common method used for diagnosing upper gastrointestinal diseases, is often limited by the presence of foam and mucous. Thus, this study was designed to detect whether the combination of simethicone with N-acetyl cysteine (NAC) as premedication before EGD improves mucosal visualization. Patients and methods A total of 768 consenting patients were enrolled in this prospective, double-blind, randomized placebo-controlled trial in four groups (A: simethicone + N-acetyl cysteine; B: simethicone alone; C: NAC alone; and D: placebo). After 20 minutes of consuming the corresponding solution, EGD was done and multiple images were obtained from the esophagus, stomach, and duodenum. Based on the various images obtained, the study parameters were calculated. Statistical Analysis Software (SAS) was used to analyze the results using Kruskal-Wallis with the Bonferroni correction method. Results The study population consisted of 57 % men and the mean age was 44.18 years. Each group was randomized with 192 participants. Group A (combination of simethicone + NAC) premedication had the lowest total mucosal visibility score of 8.31, a significantly lower score for mucous/bubbles obscuring the vision, and less time to complete the procedure. Also, 81 % of the participants in group A did not require flushing to clear the mucous/bubbles. There were no side effects due to this premedication in any of the groups. Conclusions Using simethicone and NAC combined for premedication may improve the quality of EGD.

A combination of N-acetyl cysteine and propolis attenuates oxidative-inflammatory parameters during COPD exacerbation.

The aim of this study was to determine any differences in oxidative stress and inflammation parameters in COPD patients treated with either N-acetyl cysteine (NAC) alone or with NAC in combination with propolis (NACP). Forty COPD patients in the exacerbation phase were enrolled into the study and were treated with either NAC (NAC group; n=20) or NACP (NACP group; n=20) twice daily for one month. Redox status was determined by measuring superoxide anion (O2.-), advanced oxidation protein products (AOPP), total oxidative status (TOS), prooxidative-antioxidant balance (PAB), malondialdehyde (MDA), ischemia modified albumin (IMA) and several other antioxidant markers: superoxide dismutase (SOD), paraoxonase 1 (PON1), total sulfhydryl groups (SHG) and total antioxidant status (TAS). Interleukins 6, 8 and 17 were measured as markers of inflammatory status. Both groups had similar socio-demographic and clinical characteristics. After treatment significantly higher SHG [0.446 (0.395-0.516) vs. 0.292 (0.270-0.325), p<0.001] and significantly lower TOS - 50.6 [49.7-53.4 vs. 73.2 (50.9-84.6), p<0.05] - and IMA [0.650 (0.629-0.682) vs. 0.709 (0.667-0.756), p<0.05] - were found in the NACP group compared to the NAC group. Factorial analysis indicated a larger oxidative stress-inflammatory load in the NAC group after treatment. From an oxidative stress and inflammatory status perspective, treatment with NACP was more successful than with NAC. The inclusion of propolis into therapy for COPD patients, especially those in the exacerbation phase, could prove beneficial.

High Activity of N-Acetylcysteine in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniae and Acinetobacter baumannii.

Aim: The aim of the study was to evaluate the in vitro activity of N-acetylcysteine (NAC), alone or in combination with beta-lactams, against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab). Methods: The antibacterial activity of each compound was tested by broth microdilution and the synergism was evaluated by the checkerboard method. Killing studies of NAC alone and in combination with beta-lactams were performed. Bacterial morphological changes were investigated with scanning electron microscopy (SEM). Results: Overall, 30 strains were included (15 CR-Kp and 15 CR-Ab). The NAC Minimal Inhibitory Concentrations (MIC)50/90 were 5/5 and 2.5/5 mg/mL for CR-Kp and CR-Ab, respectively. For both microorganisms, NAC, in addition to beta-lactams (meropenem for CR-Kp, meropenem and ampicillin/sulbactam for CR-Ab, respectively), was able to enhance their activity. The killing studies showed a rapid and concentration-dependent activity of NAC alone; the addition of NAC to meropenem or ampicillin/sulbactam at subinhibitory concentrations induced a fast and lasting bactericidal activity that persisted over time. The SEM analyses showed evident morphological alterations of the bacterial cells following incubation with NAC, alone and in combination with meropenem. Conclusions: NAC demonstrated a high in vitro activity against CR-Kp and CR-Ab and was able to enhance beta-lactams’ susceptibility in the tested strains. The preliminary data on the SEM analyses confirmed the in vitro results.

Better together? Treating traumatic brain injury with minocycline plus N-acetylcysteine.

Traumatic brain injury has a complex pathophysiology that produces both rapid and delayed brain damage. Rapid damage initiates immediately after injury. Treatment of traumatic brain injury is typically delayed many hours, thus only delayed damage can be targeted with drugs. Delayed traumatic brain injury includes neuroinflammation, oxidative damage, apoptosis, and glutamate toxicity. Both the speed and complexity of traumatic brain injury pathophysiology present large obstacles to drug development. Repurposing of Food and Drug Administration-approved drugs may be a highly efficient approach to get therapeutics to the clinic. This review examines the preclinical outcomes of minocycline and N-acetylcysteine as individual drugs and compares them to the minocycline plus N-acetylcysteine combination. Both minocycline and N-acetylcysteine are Food and Drug Administration-approved drugs with pleiotropic therapeutic effects. As individual drugs, minocycline and N-acetylcysteine are well tolerated, with known pharmacokinetics, and enter the brain through an intact blood-brain barrier. At concentrations greater than needed for anti-microbial action, minocycline is a potent anti-inflammatory minocycline, also acts as an antioxidant and inhibits multiple enzymes that promote brain injury including metalloproteases, caspases, and polyADP-ribose-polymerase-1. N-acetylcysteine alone is also an antioxidant. It increases brain glutathione, prevents lipid oxidation, and protects mitochondria. N-acetylcysteine also acts as an anti-inflammatory as well as increases extracellular glutamate by activating the Xc cystine-glutamate anti-transporter. These multiple actions of minocycline and N-acetylcysteine have made them attractive candidates to treat traumatic brain injury. When first dosed within the one hour after injury, either minocycline or N-acetylcysteine improves a diverse set of therapeutic outcome measures in multiple traumatic brain injury animal models. A small number of clinical trials for traumatic brain injury have established the safety of minocycline or N-acetylcysteine and suggested that either drug has some efficacy. Preclinical studies have shown that minocycline plus N-acetylcysteine have positive synergy resulting in therapeutic effects and a more prolonged therapeutic time window not seen with the individual drugs. This review compares the actions of minocycline and N-acetylcysteine, individually and in combination. Evidence supports that the combination has greater utility to treat traumatic brain injury than the individual drugs.

2.3 PSYCHOPHARMACOLOGICAL TREATMENT OF ADOLESCENTS WITH CANNABIS USE DISORDER

Societal perceptions and cannabis use patterns are changing in the era of marijuana legalization. In context of these shifts, cannabis use disorder (CUD) among adolescents are of growing concern given their association with adverse health outcomes. Evidence-based data are needed to guide treatment selection. The purpose of this presentation is to systematically review benefits and harms of pharmacotherapies for the treatment of adolescent CUD and comorbid mental health disorders with CUD. A systematic review of peer-reviewed studies was conducted using PubMed/MEDLINE and Cochrane databases. Studies were selected if they were a clinical trial, included participants aged 13 to 25 years, and examined medication (alone or in combination with psychosocial interventions) for treatment of CUD or comorbid mental health disorders with CUD. The qualitative review was supplemented with subgroup analyses of adolescents with ADHD and comorbid CUD and young adults (18 to 25 years old) with CUD from NIDA clinical trial network (CTN)'s 0028 and 0053 trials. Six clinical trials (5 controlled, 1 open-label) were identified examining 4 mechanistically different medications (N-acetylcysteine, topiramate, fluoxetine, OROS-methylphenidate) in 675 participants (29% female, 66% White; age range: 14 to 25 years). Four of the trials examined pharmacotherapies for CUD, and 2 trials examined medication in combination with CBT for mental health disorders (depression and ADHD) comorbid with CUD. Across 2 adolescent trials and a subgroup analysis of young adults from the ACCENT study (0053), N-acetylcysteine treatment in combination with contingency management doubled the odds of having a negative urine cannabinoid test (OR = 2.0). Other medications tested showed mixed results including limited separation from background CBT intervention and low tolerability/high side-effect burden. Data on pharmacotherapies for adolescent CUD remain scarce, with only 4 medications tested in controlled trials to date. Based on this limited data set, findings across drug classes have been mixed, with one exception: accumulating evidence suggests a possible role for N-acetylcysteine in combination with behavioral treatment for CUD in young people.

Effect of N-Acetylcysteine in Combination with Antibiotics on the Biofilms of Three Cystic Fibrosis Pathogens of Emerging Importance.

Cystic fibrosis (CF) is a genetic disorder causing dysfunctional ion transport resulting in accumulation of viscous mucus that fosters chronic bacterial biofilm-associated infection in the airways. Achromobacter xylosoxidans and Stenotrophomonas maltophilia are increasingly prevalent CF pathogens and while Burkholderia cencocepacia is slowly decreasing; all are complicated by multidrug resistance that is enhanced by biofilm formation. This study investigates potential synergy between the antibiotics ciprofloxacin (0.5–128 µg/mL), colistin (0.5–128 µg/mL) and tobramycin (0.5–128 µg/mL) when combined with the neutral pH form of N-Acetylcysteine (NACneutral) (0.5–16.3 mg/mL) against 11 cystic fibrosis strains of Burkholderia, Stenotrophomonas and Achromobacter sp. in planktonic and biofilm cultures. We screened for potential synergism using checkerboard assays from which fraction inhibitory concentration indices (FICI) were calculated. Synergistic (FICI ≤ 0.5) and additive (0.5 > FICI ≥ 1) combinations were tested on irreversibly attached bacteria and 48 h mature biofilms via time-course and colony forming units (CFU/mL) assays. This study suggests that planktonic FICI analysis does not necessarily translate to reduction in bacterial loads in a biofilm model. Future directions include refining synergy testing and determining further mechanisms of action of NAC to understand how it may interact with antibiotics to better predict synergy.

N-acetyl cysteine in combination with forelimbs remote ischemic preconditioning improves the contrast-induced nephropathy: an in-vivo experimental study.

N-acetyl cysteine in combination with forelimbs remote ischemic preconditioning improves the contrast-induced nephropathy: an in-vivo experimental study.

In vitro efficacy of N-acetylcysteine in combination with antimicrobial agents against Pseudomonas aeruginosa in canine otitis externa

In vitro efficacy of N-acetylcysteine in combination with antimicrobial agents against Pseudomonas aeruginosa in canine otitis externa

TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation

TRMU is a nuclear gene crucial for mitochondrial DNA translation by encoding tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase, which thiolates mitochondrial tRNA. Biallelic pathogenic variants in TRMU are associated with transient infantile liver failure. Other less common presentations such as Leigh syndrome, myopathy, and cardiomyopathy have been reported. Recent studies suggested that provision of exogenous L-cysteine or N-acetylcysteine may ameliorate the effects of disease-causing variants and improve the natural history of the disease. Here, we report six infants with biallelic TRMU variants, including four previously unpublished patients, all treated with exogenous cysteine. We highlight the first report of an affected patient undergoing orthotopic liver transplantation, the long-term effects of cysteine supplementation, and the ability of the initial presentation to mimic multiple inborn errors of metabolism. We propose that TRMU deficiency should be suspected in all children presenting with persistent lactic acidosis and hypoglycemia, and that combined N-acetylcysteine and L-cysteine supplementation should be considered prior to molecular diagnosis, as this is a low-risk approach that may increase survival and mitigate the severity of the disease course.

The combination of N-acetylcysteine and cyclosporin A reduces acetaminophen-induced hepatotoxicity in mice

ABSTRACT Acetaminophen (APAP)-induced hepatotoxicity is the most common cause of acute liver failure in worldwide. N-acetyl cysteine (NAC) is used as the APAP antidote. Cyclosporin A (CsA) is suppressed mitochondrial damage by binding cyclophilin, a mitochondrial pore transport component. The study aimed to evaluate the effects of NAC, CsA, and NAC+CsA treatments on APAP-induced hepatotoxicity in mice. Mice were randomly divided into five groups (n = 6). 400 mg/kg/ip/single dose APAP, 1200 mg/kg/i.p/single dose NAC and 50 mg/kg/i.p/single dose CsA were performed. Light and electron microscopic alterations were investigated in liver samples. Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and liver glutathione (GSH) were analyzed. 3-nitrotyrosine and cytochrome c immunoreactivities were evaluated in liver tissue. Here, we found that APAP leads to histopathological and ultrastructural changes in mice liver. Also, APAP increased cytochrome c and 3-nitrotyrosine immunopositive staining. Besides, a significant decrease in liver GSH and an increase in serum AST and ALT levels were detected in the APAP group. Interestingly, NAC+CsA treatment improved histological alterations, cytochrome c, and 3-nitrotyrosine immunoreactivities and liver GSH, serum AST/ALT levels caused by APAP. We suggest that the combination of NAC and CsA reduces acetaminophen-induced hepatotoxicity in mice.

Renal protective effect of N-acetylcysteine with stepwise ramping voltage against extracorporeal shock wave lithotripsy-induced renal injury: a prospective randomized trial

To evaluate the role of combination of N-acetylcysteine with stepwise ramping voltage in renal protection against the ischemic, vascular and oxidative effects of extracorporeal shock wave lithotripsy. A prospective randomized trial on 164 adult patients scheduled for ESWL for single renal stones. Patients with radio-lucent stones, diabetes, hypertension, febrile UTI, and preoperative albuminuria were excluded from the study. Patients were randomized into one of four groups. Group A patients received maximal fixed voltage of ESWL. Group B patients received stepwise ramping voltage of ESWL. Group C patients received fixed maximal voltage with N-acetylcysteine (NAC) 600mg/bid from 48h before to 24h after the procedure. Group D patients received gradual ramping voltage with NAC. Urinary β2-microglobulin, 24h albumin and N-acetyl-β-D-glucosaminidase/creatinine ratio at 1day and 5days post-ESWL and the stone free rate at 2weeks were measured. Group D was the only group that showed no significant difference pre and post ESWL in urinary albumin, β2-microglobulin and N-acetyl-β-D-glucosaminidase/creatinine ratio. Post hoc analysis revealed no significant difference between group B and group C in albumin, β2-microglobulin N-acetyl-β-D-glucosaminidase/creatinine ratio, but both of them had significantly lower levels than group A and significantly higher levels than group D. There was no statistically significant difference between all groups in the stone free rate at 2weeks. N-acetylcysteine protects the kidney against ESWL-induced renal injuries especially if combined with stepwise ramping voltage.