-
International Journal of Environmental... Jan 2022Deltamethrin (DLM) is a synthetic pyrethroid with anti-acaricide and insecticidal properties. It is commonly used in agriculture and veterinary medicine. Humans and...
Deltamethrin (DLM) is a synthetic pyrethroid with anti-acaricide and insecticidal properties. It is commonly used in agriculture and veterinary medicine. Humans and animals are exposed to DLM through the ingestion of polluted food and water, resulting in severe health issues. -acetylcysteine (NAC) is a prodrug of L-cysteine, the precursor to glutathione. It can restore the oxidant-antioxidant balance. Therefore, this research aimed to examine whether NAC may protect broiler chickens against oxidative stress, at the level of biochemical and molecular alterations caused by DLM intoxication. The indicators of liver and kidney injury in the serum of DLM-intoxicated and NAC-treated groups were examined. Furthermore, lipid peroxidation, antioxidant markers, superoxide dismutase activity, and apoptotic gene expressions (caspase-3 and Bcl-2) were investigated. All parameters were significantly altered in the DLM-intoxicated group, suggesting that DLM could induce oxidative damage and apoptosis in hepato-renal tissue. The majority of the changes in the studied parameters were reversed when NAC therapy was used. In conclusion, by virtue of its antioxidant and antiapoptotic properties, NAC enabled the provision of significant protection effects against DLM-induced hepato-renal injury.
Topics: Acetylcysteine; Animals; Antioxidants; Apoptosis; Chickens; Humans; Kidney; Liver; Nitriles; Oxidative Stress; Pyrethrins
PubMed: 35055458
DOI: 10.3390/ijerph19020638 -
Neuroscience Sep 2020The tryptophan metabolite kynurenic acid (KYNA) may play an important role in normal and abnormal cognitive processes, most likely by interfering with α7 nicotinic and...
The tryptophan metabolite kynurenic acid (KYNA) may play an important role in normal and abnormal cognitive processes, most likely by interfering with α7 nicotinic and NMDA receptor function. KYNA is formed from its immediate precursor kynurenine either by non-enzymatic oxidation or through irreversible transamination by kynurenine aminotransferases. In the mammalian brain, kynurenine aminotransferase II (KAT II) is the principal enzyme responsible for the neosynthesis of rapidly mobilizable KYNA, and therefore constitutes an attractive target for pro-cognitive interventions. N-acetylcysteine (NAC), a brain-penetrant drug with pro-cognitive efficacy in humans, has been proposed to exert its actions by increasing the levels of the anti-oxidant glutathione (GSH) in the brain. We report here that NAC, but not GSH, inhibits KAT II activity in brain tissue homogenates from rats and humans with IC values in the high micromolar to low millimolar range. With similar potency, the drug interfered with the de novo formation of KYNA in rat brain slices, and NAC was a competitive inhibitor of recombinant human KAT II (Ki: 450 μM). Furthermore, GSH failed to S-glutathionylate recombinant human KAT II treated with the dithiocarbamate drug disulfiram. Shown by microdialysis in the prefrontal cortex of rats treated with kynurenine (50 mg/kg, i.p.), peripheral administration of NAC (500 mg/kg, i.p., 120 and 60 min before the application of kynurenine) reduced KYNA neosynthesis by ∼50%. Together, these results suggest that NAC exerts its neurobiological effects at least in part by reducing cerebral KYNA formation via KAT II inhibition.
Topics: Acetylcysteine; Animals; Kynurenic Acid; Kynurenine; Rats; Transaminases
PubMed: 32768617
DOI: 10.1016/j.neuroscience.2020.07.049 -
Journal of Thrombosis and Haemostasis :... Jan 2023Trimethylamine N-oxide (TMAO), a gut microbe-generated metabolite, elicits thrombotic events by enhancing platelet reactivity; however, no studies have reported the...
BACKGROUND
Trimethylamine N-oxide (TMAO), a gut microbe-generated metabolite, elicits thrombotic events by enhancing platelet reactivity; however, no studies have reported the effects of TMAO on the metabolism of and response to clopidogrel.
OBJECTIVES
To determine whether choline and TMAO could significantly impair metabolic activation of and platelet response to clopidogrel in choline- or TMAO-fed mice and the mechanisms involved.
METHODS
Male mice were fed with vehicle control (Ctrl), TMAO, choline alone or in combination with 3,3-dimethyl-1-butanol, N-acetyl-L-cysteine, or ML385 for 14 days and then treated with Ctrl or a single oral dose of clopidogrel. Plasma TMAO, protein levels of clopidogrel-metabolizing enzymes in the liver, plasma concentrations of clopidogrel and its metabolites, and adenosine diphosphate-induced platelet aggregation and activation were measured. In addition, HepG2 cells were treated with Ctrl or TMAO alone or in combination with N-acetyl-L-cysteine, ML385, or apocynin, and CES1, reactive oxygen species (ROS), and Nrf2 protein levels were measured, respectively.
RESULTS
TMAO significantly increased Ces1 protein expression and activity and clopidogrel hydrolysis in the liver as well as intracellular ROS and CES1 levels and Nrf2 nucleus translocation in HepG2 cells but decreased the formation of clopidogrel active metabolite and impaired platelet response to clopidogrel. Furthermore, concomitant use of 3,3-dimethyl-1-butanol, N-acetyl-L-cysteine, or ML385 effectively reversed choline- or TMAO-induced impairment of inhibition of platelet aggregation by clopidogrel in mice, respectively.
CONCLUSIONS
Choline and TMAO impair the metabolic activation of and platelet response to clopidogrel through the activation of the NOX-dependent ROS/Nrf2/CES1 pathway, suggesting novel strategies for overcoming clopidogrel resistance from bench to bedside.
Topics: Male; Animals; Mice; Choline; Clopidogrel; NF-E2-Related Factor 2; Reactive Oxygen Species; Activation, Metabolic; Acetylcysteine
PubMed: 36695375
DOI: 10.1016/j.jtha.2022.10.010 -
Critical Reviews in Toxicology Dec 2023Metal phosphides are highly toxic pesticides that result in high morbidities and mortalities worldwide. This systematic review included 350 studies that fulfilled the... (Review)
Review
Metal phosphides are highly toxic pesticides that result in high morbidities and mortalities worldwide. This systematic review included 350 studies that fulfilled the eligibility criteria. There were significant rising trends of studies on acute aluminum phosphide (AlP) and zinc phosphide (ZnP) poisoning (-values = <.001), pointing to an increased number of phosphide-intoxicated patients. Acute AlP poisoning studies represented 81%, 89.3%, and 97.7% of all descriptive, analytical, and experimental interventional studies included in this review, respectively. High AlP poisoning mortality explains great research interest in AlP poisoning. Thus, after 2016, nearly half (49.7%) of studies on acute AlP poisoning were issued. Also, 78.82% of experimental interventional studies on AlP poisoning were published after 2016. The trends of in-vitro, animal, and clinical studies on AlP poisoning significantly increased with -values equal to .021, <.001, and <.001, respectively. Seventy-nine treatment modalities for acute AlP poisoning were pooled from 124 studies; 39 management-related case reports, 12 in-vitro studies, 39 animal studies, and 34 clinical studies. All therapeutic modalities were summarized to formulate an integrated and comprehensive overview. For clinicians, therapeutic modalities significantly decreased mortality of acute AlP poisoning in clinical trials included extracorporeal membrane oxygenation (ECMO), N-acetyl cysteine (NAC), vitamin E, glucose-insulin-potassium (GIK) infusion, fresh packed RBCs infusion, and GIT decontamination using oils. However, meta-analyses are needed to provide solid evidence regarding their efficacies. To date, there is no effective antidote nor evidence-based standardized protocol for managing acute AlP poisoning. This article outlined the potential research gaps in phosphide poisoning that might promote and direct future medical research in this context.
Topics: Animals; Pesticides; Evidence Gaps; Antidotes; Acetylcysteine; Aluminum Compounds
PubMed: 37387512
DOI: 10.1080/10408444.2023.2225539 -
The Journal of Veterinary Medical... Sep 2023Cadmium is a major environmental pollutant and a highly toxic metal. It was aimed to determine the effects of pomegranate peel extract (PPE), N-acetylcysteine (NAC)...
Cadmium is a major environmental pollutant and a highly toxic metal. It was aimed to determine the effects of pomegranate peel extract (PPE), N-acetylcysteine (NAC) alone and along with Ornipural on cadmium-induced toxicity. Forty-six Wistar Albino male rats were divided into 6 groups and the groups were formed into healthy control, Cadmium group (5 mg/kg/day, oral), Cadmium + Pomegranate peel extract (500 mg/kg, oral), Cadmium + N-acetylcysteine (100 mg/kg, oral), Cadmium + Pomegranate peel extract (500 mg/kg, oral) + Ornipural (1 mL/kg, subcutaneous) and Cadmium + N-acetylcysteine (100 mg/kg, oral) + Ornipural (1 mL/kg, subcutaneous). Cadmium accumulated heavily in both liver and kidney tissue. The administration of N-acetylcysteine and pomegranate peel extract alone reduced cadmium levels in both tissues. N-acetylcysteine treatment prevented the increase in ALT and MDA levels by cadmium damage. N-acetylcysteine + Ornipural treatment inhibited the increase in liver 8-OHdG level in the liver. N-acetylcysteine and N-acetylcysteine + Ornipural treatments prevented the reduced serum MMP2 level. N-acetylcysteine and Pomegranate peel extract + Ornipural treatments significantly reduced the increased liver iNOS level in the liver. In conclusion, NAC therapy may be a successful treatment option for cadmium toxicity. However, further research is needed on the effects of PPE and Ornipural combinations for the treatment of cadmium toxicity. In future studies, various doses of these treatment options (with chelators) should be investigated for cadmium toxicity.
Topics: Rats; Animals; Acetylcysteine; Antioxidants; Rats, Wistar; Cadmium; Pomegranate; Plant Extracts
PubMed: 37495528
DOI: 10.1292/jvms.22-0375 -
Clinical Toxicology (Philadelphia, Pa.) Apr 2022Previous literature suggests a laboratory interference of n-acetylcysteine (NAC) with prothrombin time (PT) and the international normalized ratio (INR). Early...
BACKGROUND
Previous literature suggests a laboratory interference of n-acetylcysteine (NAC) with prothrombin time (PT) and the international normalized ratio (INR). Early publications focused on this interaction in the setting of an acetaminophen overdose and evaluated the INR of patients receiving intravenous NAC. However, there is limited literature describing the concentration-effect relationship of NAC to INR measurement in the absence of acetaminophen-induced hepatotoxicity at therapeutic NAC concentrations. The purpose of the study is to quantify the degree of interference of NAC on INR values at therapeutic concentrations correlating to each infusion of the regimen (ex. bag 1: 550 mcg/mL, bag 2: 200 mcg/mL, bag 3: 35 mcg/mL, double bag 3: 70 mcg/mL) and at supratherapeutic concentrations .
METHODS
Blood samples were obtained from study volunteers. Each blood sample was transferred into vials containing 0.3 mL buffered sodium citrate 3.2% and spiked with various concentrations of NAC for final concentrations of 0, 35, 70, 200, 550, 1000, 2000, and 4000 mcg/mL. The samples were centrifuged and tested to determine PT and INR on two separate machines: Siemens CS-2500 and Stago SN1114559. We would require a sample size of 6 to achieve a power of 80% and a level of significance of 1.7% (two-sided). Differences between INRs at varying concentrations were determined by Friedman's test. For multiple comparisons, post hoc analysis was performed using Wilcoxon signed-rank test with Bonferroni adjustment. Analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC).
RESULTS
Participants included 11 healthy subjects: 8 males, 3 females, median age 30 years (range 25 - 58). Median and interquartile ranges (IQR) INR for the baseline samples were 1.09 (IQR 1.05, 1.16) for Siemens and 1.03 (IQR 0.99, 1.11) for Stago analyzers. There was a significant difference in INR between the therapeutic concentrations (baseline, 35, 70,200, or 550 µg/mL) (Siemens = .0008, Stago < .0001). The 550 µg/mL concentration with the Siemens analyzer was the only one compared separately and found to be significantly greater than the baseline (1.07 vs 1.22, = .02). For the Stago analyzer the 200 µg/mL and 500 µg/mL were compared and found to be significantly different from baseline (1.00 vs 1.07 and 1.19, adjusted = .02 and = .03, respectively). The largest INR increase seen was in one subject from a baseline of 1.07-1.32 with the 550 µg/mL concentration. Increases in concentrations to supratherapeutic levels resulted in a statistically significant non-linear increase in INR for all concentrations (Siemens < .0001, Stago < .0001). All of these concentrations were found to be significantly different from baseline (all adjusted < .05).
CONCLUSION
Although it was found that at therapeutic concentrations the presence of NAC affects INR measurements on two different machines, the change is of little clinical relevance. Supratherapeutic concentrations of NAC affect INR significantly, but the clinical utility of those results is limited by the rarity of those concentrations being measured.
Topics: Acetaminophen; Acetylcysteine; Administration, Intravenous; Adult; Female; Humans; International Normalized Ratio; Male; Middle Aged; Prothrombin Time
PubMed: 34549665
DOI: 10.1080/15563650.2021.1979232 -
European Endodontic Journal Oct 2022To evaluate the solubility, pH, antimicrobial action, and cytotoxicity of ambroxol hydrochloride (AMB), N-acetylcysteine (NAC), and calcium hydroxide (CH) pastes for use... (Comparative Study)
Comparative Study
OBJECTIVE
To evaluate the solubility, pH, antimicrobial action, and cytotoxicity of ambroxol hydrochloride (AMB), N-acetylcysteine (NAC), and calcium hydroxide (CH) pastes for use as intracanal medications.
METHODS
Solubility was determined by micro-CT, based on the paste volume remaining after immersion in water for 7 days. pH was measured by immersing acrylic tubes containing the pastes in ultrapure water and then measuring pH after 3 hours, 3 days, and 7 days. Antimicrobial action against Enterococcus faecalis was assessed based on the percentage of living cells, using the live/dead staining method under confocal microscopy. Cytotoxicity was assessed based on the cell viability of L929 fibroblast-like cells after 6, 24, and 48 hours. Cytotoxicity data were compared using the ANOVA and Tukey tests, and the antimicrobial data were compared using the Kruskal-Wallis and Dunn tests. The significance level used was 5% (α=0.05).
RESULTS
The solubility values for all the study groups were significantly different (P<0.05), where the highest values were for NAC, followed by AMB, and then CH. Likewise, the pH levels were all significantly different (P<0.05), where NAC and AMB levels were acidic, and CH levels were alkaline. The antimicrobial action of AMB was significantly higher than that of CH (P<0.05), and that of NAC was also higher than that of CH, albeit not significantly. AMB and NAC were more cytotoxic than CH, and higher dilutions of CH promoted higher cell viability levels than lower dilutions of the same paste (P<0.05).
CONCLUSION
The NAC and AMB pastes were more soluble and cytotoxic than the CH paste and had acidic pH levels. The AMB paste displayed the highest antimicrobial action against Enterococcus faecalis biofilm.
Topics: Acetylcysteine; Ambroxol; Anti-Infective Agents; Calcium Hydroxide; Chemical Phenomena; Enterococcus faecalis; Water
PubMed: 36217638
DOI: 10.14744/eej.2022.30306 -
BMC Oral Health Sep 2022This scoping review systematically summarized the available evidence about the efficacy of N-acetyl cysteine (NAC) as an intracanal antibacterial and/or... (Review)
Review
BACKGROUND
This scoping review systematically summarized the available evidence about the efficacy of N-acetyl cysteine (NAC) as an intracanal antibacterial and/or anti-inflammatory.
METHODS
PubMed, Scopus, Web of Science, and Google scholar search engines/databases were searched up to February 2022 to retrieve relevant studies. The studies were evaluated for eligibility criteria, and identifying relevant studies.
RESULTS
Out of 193 studies, 15 fulfilled the inclusion criteria and were processed for data extraction. Thirteen in vitro studies assessed antibacterial/antibiofilm efficacy of NAC, and reported good and promising efficacy: NAC was found as efficacious as the comparators (chlorhexidine, sodium hypochlorite, calcium hydroxide), or even showed higher efficacy. Regarding the anti-inflammatory efficacy of NAC, one in vitro study found it equivalent to, while one clinical trial revealed it more efficacious than calcium hydroxide.
CONCLUSIONS
There is accumulating evidence on the anti-microbial and anti-inflammatory efficacy of NAC in context of endodontics. However, further clinical trials with robust methodology and objective and reliable clinical, biological and microbial outcomes are warranted to translate its use for clinical practice on humans.
Topics: Acetylcysteine; Anti-Bacterial Agents; Anti-Inflammatory Agents; Calcium Hydroxide; Chlorhexidine; Humans
PubMed: 36096839
DOI: 10.1186/s12903-022-02433-6 -
Urolithiasis Dec 2023To assess the effect of co-trimoxazole and N-acetylcysteine (NAC), alone and in combination, on bacterial adherence to biofilm formed on ureteral stent surfaces. This... (Randomized Controlled Trial)
Randomized Controlled Trial
To assess the effect of co-trimoxazole and N-acetylcysteine (NAC), alone and in combination, on bacterial adherence to biofilm formed on ureteral stent surfaces. This prospective randomized study was conducted on 636 patients who underwent double J ureteral stent insertion after variable urological procedures. Patients were randomized into four groups: A (n = 165), no antibiotics or mucolytics during stent indwelling; B (n = 153), oral NAC (200 mg/day for children aged < 12 years old and 600 mg/day for adults) during stent indwelling; C (n = 162), oral co-trimoxazole (2 mg TMP/kg/day) during stent indwelling; and D (n = 156), both oral NAC and co-trimoxazole during stent indwelling. Two weeks following double J stent (JJ stent) insertion, urinalysis was performed on all patients and urine culture was done for all the patients at the day of double J stent removal. The stent was removed 2 weeks postoperatively, and a stent segment sized 3-5 cm from the bladder segment of the stent was sent for culture. Positive stent cultures were found in 63.6% (105/165), 43.1% (66/153), 37% (60/162), and 19.2% (30/156) patients of groups A, B, C, and D, respectively. E. coli was the organism most commonly isolated from the stent culture in all groups. The combination of co-trimoxazole and NAC was more effective in reducing bacterial adherence on ureteral stent surfaces than either alone.
Topics: Adult; Child; Humans; Acetylcysteine; Trimethoprim, Sulfamethoxazole Drug Combination; Prospective Studies; Escherichia coli; Ureter; Stents; Bacteria
PubMed: 38079000
DOI: 10.1007/s00240-023-01508-5 -
Oxidative stress and viral Infections: rationale, experiences, and perspectives on N-acetylcysteine.European Review For Medical and... Nov 2022This article explores current evidence on the role of oxidative stress in viral infections, and on the use of antioxidant drugs as adjunctive treatment. MEDLINE/PubMed...
This article explores current evidence on the role of oxidative stress in viral infections, and on the use of antioxidant drugs as adjunctive treatment. MEDLINE/PubMed was searched for appropriate keywords, and preclinical and clinical studies with reviews were retrieved and examined by authors. Old and current evidence shows that GSH content reduction is the main mechanism of redox imbalance in viral-infected cells. Clinical studies found that GSH levels are depleted in patients with viral infections such as HIV and SARS-CoV. Viral infections activate inflammation through different pathways, and several of these mechanisms are related to oxidative stress. NAC is a precursor of GSH, and many of its intracellular effects are mediated by GSH replenishment, but it also activates some anti-inflammatory mechanisms. NAC has an excellent safety profile and better oral and topical bioavailability than GSH. These characteristics make NAC a suitable option as a repurposed drug. Adjunctive antioxidant treatment may improve the outcomes of antiviral therapies. Current evidence supports the rationale for this practice and some clinical experience showed encouraging results.
Topics: Humans; Acetylcysteine; Antioxidants; Oxidative Stress; Virus Diseases; Inflammation
PubMed: 36459039
DOI: 10.26355/eurrev_202211_30395