• Journal of The Korean Society of Clinical Toxicology
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• v.4 no.2
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• pp.107-112
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• 2006

Purpose: In many Korean hospitals, serum acetaminophen concentrations in cases of overdose cannot be measured initially because of inadequate laboratory facilities. Under these circumstances, physicians base the administration of the antidote, N-acetylcysteine, on ingestion amounts as determined by initial history taking. We therefore examined the correlated between ingested amounts and serum acetaminophen concentrations. Methods: Medical records were reviewed retrospectively for patients who presented to the ED with acetaminophen overdose between January 2002 and March 2006. Fifty-nine patients were recruited and sixteen patients were excluded. The forty-three remaining patients were placed into either the high-risk or low-risk group based on their ingested amount (140 mg/kg), and were separately categorized into the toxic or non-toxic group based on their serum acetaminophen concentrations, according to the Rurnack-Matthew nomogram. Results: Ten patients (83.3%) among twelve in the high-risk group were found to have non-toxic serum concentrations, and just one patient (3.2%) among thirty-one in the low-risk group fell into the toxic group based on their serum concentrations. The sensitivity and specificity of risk stratification of the ingested amount as a predictor of intoxication requiring antidote therapy were 66.7% and 75.0%, respectively. Conclusion: This study suggests that the therapeutic decision for acetaminophen overdose should not be based solely on ingested amount only, but requires assessment of acetaminophen concentration.

• Journal of The Korean Society of Clinical Toxicology
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• v.10 no.2
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• pp.97-102
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• 2012

Purpose: Serious acetaminophen (AAP) poisoning causes hepatotoxicity. N-acetylcysteine (NAC) is the most effective therapy for AAP poisoning and can be administered orally and intravenously (IV). Several studies have compared the efficacy of these two routes of administration and the results have been controversial. The purpose of this study was to compare the efficacy of oral and IV NAC for the prevention of hepatic toxicity in Korean patients whose serum AAP levels were higher than normal. Methods: A retrospective before/after study was performed, in which the patients presented to the emergency department with an AAP overdose from February 1995 to March 2012. A 3-day oral NAC regimen was used in the beginning, and a 20-hr intravenous regimen was then used from 2007. This study assessed the complications of an AAP overdose, such as hepatotoxicity, hepatic failure and renal failure as well as the side effects of the treatment regimen. Results: A total of 41patients was enrolled in this study. The median ALT and AST were 63 (IU/L) and 57 (IU/L) for the oral NAC treated patients, and 14 (IU/L) and 20 (IU/L) for the IV NAC treated patients (p=0.004 and p=0.001, respectively). The incidence of complications was similar in the treatment groups (p=0.399). Among the patients, 7 patients developed hepatotoxicity and were treated successfully with oral or IV NAC. Conclusion: This study suggests that IV NAC and oral NAC can prevent and successfully treat hepatic toxicity in patients whose serum AAP levels are higher than normal.

• Journal of fish pathology
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• v.32 no.1
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• pp.21-28
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• 2019

It has been reported that various anti-oxidant substances stimulate non-specific immune responses in fishes. In this study it was examined whether N-acetylcysteine (NAC), a precusor for anti-oxidant glutathione (GSH) synthesis, can modulate non-specific immune function in Far Eastern catfish Silurus asotus. Immune functions were assessed using the respiratory burst activity monitored by chemiluminescence (CL) responses in isolated leucocyte. NAC stimulated CL responses with doses of 10 or 100 mg/kg, but not with 1 mg/kg after 48 hr injection. It was observed with 10 mg/kg NAC that CL activity continued to elevate from 24 hr through 96 hr post-dosing, and returned to the near preinjection level by 10 days. To understand whether NAC can also activate CL activity in vitro, NAC was directly added to isolated catfish leucocytes. It was observed, however, that NAC can not stimulate CL at reasonable concentration ranges in vitro. As NAC is a precursor for the strong anti-oxidant glutathione (GSH), a putative immune stimulator, it was assessed whether GSH can also stimulate CL responses. Observed results show that GSH activated CL both in vivo and in vitro. The data obtained collectively support the proposition that NAC indirectly stimulates non-specific immune functions in catfish by enhancing GSH biosynthesis, but not by direct action of NAC. Such effects may have beneficial significance in aquaculture for practical utilization.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.3
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• pp.159-164
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• 2005

Effects of antioxidants on the established nephropathy were investigated. The experimental nephropathy was induced in rats by intravenous injection of adriamycin (2 mg/kg). Six weeks later, when proteinuria was apparent, the rats were supplemented with N-acetylcysteine (NAC, 1 g/kg/day) in drinking water for additional 6 weeks. Glomerulosclerosis score and tubulointerstitial injury index were determined by light microscopy. Expression of transforming growth factor (TGF) ${\beta}1$ and laminin ${\beta}1$ was determined in the renal cortex by reverse transcription-polymerase chain reaction, Western blotting, immunohistochemistry, and immunogold electron microscopy. The adriamycin-induced proteinuria as well as the glomerulosclerosis and tubulointerstitial injury was ameliorated by the treatment with NAC. Adriamycin increased the expression of TGF ${\beta}1$ mRNA and protein, which was ameliorated by NAC. Although the expression of laminin ${\beta}1$ mRNA was increased, adriamycin did not significantly alter that of its protein. These results indicate that antioxidants ameliorate the established nephropathy in association with normalization of overexpressed TGF ${\beta}1$.

• International Journal of Oral Biology
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• v.33 no.4
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• pp.187-195
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• 2008

Reparative dentine formation requires newly differentiated odontoblast-like cells. Therefore, identification of the molecule that stimulates the odontogenic differentiation of precursor cells in the tooth pulp will be helpful for the development of strategies to repair damaged pulp. In this study, we examined the effect of N-acetylcysteine (NAC) on the odontogenic differentiation of MDPC-23 cells, a mouse odontoblast-like cell line derived from dental papilla, and primary cultured rat dental papilla cells (RDPCs). NAC (1-30 mM) suppressed production of reactive oxygen species in MDPC-23 cells in a dose-dependent manner. Although 5 to 20 mM NAC did not alter MDPC-23 cell proliferation, 1 or 30 mM NAC significantly inhibited it. NAC enhanced mineralized nodule formation and the expression of several odontoblast differentiation-associated genes in both RDPCs and MDPC-23. This NAC stimulatory effect was significant, even at concentrations lower than 1 mM. However, NAC did not stimulate expression of bone morphogenetic protein-2, -4, or -7, which are known to enhance odontogenic differentiation. Since reactive oxygen species are also involved in the pulp toxicity of resin-based restorative materials, these results suggest that NAC may be a promising candidate for supplementation of dental restorative materials in order to enhance reparative dentine formation.

• Journal of The Korean Society of Clinical Toxicology
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• v.16 no.1
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• pp.33-41
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• 2018

Purpose: This study was conducted to evaluate the clinical efficacy of pharmacologic treatment of amatoxin poisoning patients. Methods: Literature was accessed through PubMed, EMBASE, Cochrane library, KoreaMed, KISS and KMBASE. Studies relevant to human use of pharmacologic therapy including silymarin, penicillin and N-acetylcysteine (NAC) for amanita poisoning were included. Case reports, letters, editorials and papers with insufficient information were excluded. Comparison of clinical outcomes (especially mortality and liver transplantation rate) in each study was analyzed. Results: The final analysis included 13 retrospective studies. None of these studies showed direct comparisons of individual agents. Among 12 studies comparing silymarin vs penicillin, eight showed clinical superiority of silymarin. Among eight studies comparing silymarin with NAC, six showed clinical superiority of silymarin. Among seven studies of NAC vs penicillin, five showed clinical superiority of NAC. Conclusion: This systematic review suggested that clinical superiority of various pharmacological agents used to treat amatoxin poisoning is debatable. Nevertheless, the available evidence suggests it is reasonable to consider combinations of multiple agents for patients with amanita poisoning. Further studies are required to establish a treatment regimen for amanita poisoning.

• Journal of fish pathology
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• v.25 no.1
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• pp.1-10
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• 2012

It has been reported that various anti-oxidant substances stimulate non-specific immune responses in fishes. In this study it was examined whether N-acetylcysteine (NAC), an anti-oxidant glutathione (GSH) precursor, can modulate non-specific immune parameters in 8 different fishes. NAC was intraperitoneally administered at 10 mg/kg to catfish (Silurus asotus), loach (Misgurnus mizolepis), common carp (Cyprinus carpio), crucian carp (Carassius carassius), eel (Anguilla japonica), snakehead (Channa argus), tilapia (Oreochromis niloticus) and mullet (Mugil cephalus). Forty-eight hours later, chemiluminescence (CL) response of head-kidney leukocytes and serum lysozyme activity were assessed. In all fishes except crusian carp and loach, CL responses were amplified by NAC. Lysozyme activity was increased by NAC in all fish species but not in tilapia. This result suggests that NAC stimulates non-specific immune responses in various species, and that such effects may have beneficial significance in aquaculture for practical utilization.

• Tuberculosis and Respiratory Diseases
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• v.61 no.4
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• pp.366-373
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• 2006

Background: Paraquat is extremely toxic chemical material, which generates reactive oxygen species (ROS), causing multiple organ failure. In particular, paraquat leads to irreversible progressive pulmonary fibrosis. Exaggerated cell deaths exceeding the normal repair of type II pneumocytes leads to mesenchymal cells proliferation and fibrosis. This study examined the followings; i) whether or not paraquat induces cell death in lung epithelial cells; ii) whether or not paraquat-induced cell deaths are apoptosis or necrosis; and iii) the effects of N-acetylcysteine, dexamethasone, and bcl-2 on paraquat-induced cell deaths. Methods: A549 and BEAS-2B lung epithelial cell lines were used. The cell viability and apoptosis were evalluated using a MTT assay, Annexin V staining was monitored by fluorescence microscopy, The level of bcl-2 inhibition was examined by establishing stable A549 pcDNA3-bcl-2 cell lines throung the transfection of pcDNA3-bcl-2 with the mock. Results: Paraquat decreased the cell viability in A549 and BEAS-2B cells in a dose and time dependent manner. The Annexin V assay showed that apoptosis was the type of paraquat-induced cell death. Paraquat-induced cell deaths was significantly inhibited by N-acetylcysteine, dexamethasone, and bcl-2 overexpression. The cell viability of A549 cells treated with N-acetylcysteine, and dexamethasone on the paraquat-induced cell deaths were increased significantly by 10 ~ 20%, particularly at high doses. In addition, the cell viability of A549 pcDNA3-bcl-2 cells overexpressing bcl-2 was significantly higher than the untransfected A549 cells. Conclusion: Paraquat induces apoptotic cell deaths in lung epithelial cells in a dose and time dependent manner. The paraquat-induced apoptosis of lung epithelial cells might occur through the mitochondrial pathway.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.2
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• pp.210-213
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• 2008

Hyperacute liver failure from mushroom intoxication in children is rare and has a low survival rate. We report a case of hyperacute liver failure from mushroom intoxication in a 29-month-old boy. The patient ingested a mushroom about three days prior to presentation. He was admitted to the hospital with vomiting, abdominal pain, seizures, and hematemesis. During the hospitalization the patient developed hepatic encephalopathy (stage IV-a), and a coagulopathy. He recovered fully with specific medication, Penicillin GK and N-acetylcysteine.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.475-483
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• 1994

Background: N-acetylcysteine(ACE) is used both orally and intravenously in a variety of experimental pathologies resembling human disease states which exhibit endothelial toxicity as a result of oxidative stress, including acute pulmonary oxygen toxicity, septicemia and endotoxin shock. Despite these observations in vivo, it is not certain how this thiol drug produces its protective effects. ACE is a cysteine derivative which is able to direct1y react with oxygen radicals and may also act as a cysteine and glutathione(GSH) precursor following deacetylation. In this paper, we tried to know whether the therapeutic doses of ACE can modify the inflammatory function of the neutrophils and can increase the glutathione level of plasma in chronic obstructive pulmonary disease(COPD) patients. In addition, the effect of ACE to the purified neutrophil in terms of superoxide release and glutathione synthesis were observed. Method: Firstly, we gave 600mg of ACE for seven days and compare the release of superoxide, luminol-enhanced chemiluminescence from the neutrophils, neutrophil chemotaxis, and plasma GSH levels before and after ACE treatment in COPD patients. Secondly, we observed the dose dependent effect of ACE to the purified neutrophil's superoxide release and GSH levels in vitro. Results: 1) Usual oral therapeutic doses(600mg per day) of ACE for seven days did affect neither on the neutrophil's superoxide release, chemiluminescence, chemotaxis, nor on the plasma GSH concentration in the COPD patients. 2) ACE decreases the purified neutrophil's superoxide release and increase the GSH production in dose dependent fashion in vitro. Conclusion: Despite the fact that oral ACE treatment did not affect on the neutrophil's inflammatory function and plasma GSH concentration in COPD patients in usual therapeutic doses, it decreases the superoxide release and increases the GSH production from the isolated neutrophils in high molar concentrations. These findings suggest that to obtain an antioxidative effects of ACE, it might be needed to increase the daily dosage of ACE or therapeutic duration or change the route of adminisration in COPD patients.