• Journal of Animal Science and Technology
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• v.62 no.3
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• pp.348-355
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• 2020

Cyclophosphamide, a cytotoxic anticancer agent, induces immunosuppression and has several adverse effects. N-acetylcysteine alleviates oxidative stress, liver injury, and intestinal tissue damage. The present study examined whether N-acetylcysteine modulates the adverse effects of cyclophosphamide in pigs. Miniature pigs (n = 15) were used as an experimental model to evaluate the effects of N-acetylcysteine treatment on immune reactions, liver injury, and oxidative stress after cyclophosphamide challenge. Corn-soybean meal based dietary treatments were as follows: control diet with either saline injection, cyclophosphamide injection, or 0.5% N-acetylcysteine and cyclophosphamide injection. N-acetylcysteine increased the number of immune cells and decreased TNF-α production after cyclophosphamide injection and decreased TNF-α, IFN-γ, NF-κB, and IL-8 expression and increased IL-10 expression in peripheral blood mononuclear cells. Serum levels of alanine transaminase and aspartate aminotransferase decreased, superoxide dismutase activity increased, and malondialdehyde activity decreased following N-acetylcysteine treatment after cyclophosphamide injection. N-acetylcysteine decreases immunosuppression, liver injury, and oxidative stress in cyclophosphamide-challenged miniature pigs. The present study suggests that N-acetylcysteine has therapeutic application in livestock for modulating immune reactions, liver injury, and oxidative stress.

• YAKHAK HOEJI
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• v.37 no.3
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• pp.278-285
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• 1993

The anticlastogenic effect of N-acetylcysteine was tested in vivo in mouse bone-marrow micronucleus assay. The frequencies of micronuclei induced by adriamycin (5 mg/kg i.p.) in bonemarrow cells were decreased by the oral administration of N-acetylcysteine at 12 h before adriamycin injection. The observed suppressing effect was not a reflection of a delay in the formation of micronuclei by the cytotoxic effect of N-acetylcysteine. The anticlastogenic effects of SH compound including N-acetylcysteine, cysteine, cystine, S-carboxy methylcysteine and glutathione were also investigated by the multiple pretreatment. Each SH compound was administered orally every day for 5 days and adriamycin (5 mg/kg i.p.) was injected at 24h after the last dose of test compound. N-acetylcysteine and glutathione showed significantly the suppressive effect at dose of 10 and 25 mg/kg for N-acetylcysteine and at the dose of 25 mg/kg for glutathione. Our study suggests that N-acetylcysteine is capable of protecting the chromosomal damages in the normal cells during cancer chemotherapy by adriamycin, and may act as an anticlastogen against induction of micronuclei by superoxide generating agent such as adriamycin.

• Toxicological Research
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• v.14 no.2
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• pp.177-181
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• 1998

Dithiocarbamate and mixed disulfide containing allyl functions were designed and synthesized as putative chemopreventive agents, i.e. N,N-diallyldithiocarbamate (DATC) and S-(N,N-diallyldithiocarbamoyl)-N-acetylcysteine (AC-DATC). DATC and AC-DATC were administered and the activities of cytosolic glutathione S-transferase (GST), glutathione reductase (GR) and microsomal N-nitrosodiethylamine (NDEA) deethylase were assayed in order to test the effects of these organosulfur com-pounds on the detoxification and metabolic activation system of NDEA. The amounts of hepatic glutathione (GSH and GSSG) was also determined. The administration of DATC to rats led to an increase in the activity of GR and to an inhibition of CYP2E1-mediated NDEA deethylation. AC-DATC induced the activity of GR and GST, increased the hepatic GSH content and inhibited the rate of NDEA deethylation. The level of GSSG was decreased as a consequence of the increased activity of GR. These effects may contribute to possible antimutagenic and anticarcinogenic action of the dithiocarbamates investigated.

• Toxicological Research
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• v.3 no.2
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• pp.129-141
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• 1987

Hepatocytes isolated from rats which have been pretreated with phenobarbital (80 mg/kg for 3 days), were able to take up N-acetylcysteine from surrounding medium and were able to synthesize the reduced glutathione ($GSH^{\ast}-3$) intracellularly. The N-acetylcysteine is quickly deacetylated after the uptake and increases the pool size of cysteine, which was very low initially (5 nmol/$10^6$ cells). From this increased intracellular cysteine pool, GSH was synthesized. Freshly isolated rat hepatocytes contained a high level of GSH (30 nmol/$10^6$ cells), but upon incubation with the diethylmaleate, it was markedly decreased (10 nmol/$10^6$ cells). The hepatocytes with depleted GSH have lost viability upon incubations with acetaminophen (5mM) and paraquat (2 mM). However, when the N-acetylcysteine (1 mM) was added to this incubation condition, these chemical induced hepatocellular necrosis were prevented for longer durations. This N-acetylcysteine dependent protective effect against the hepatotoxic chemicals was lost by adding methionine sulfoximine (10 mM), an inhibitor of GSH biosynthesis. Both the carbontetrachloride (5 mM) and chioroform (5 mM) added to the incubation medium caused rapid losses of GSH and cell viability, even without the prior depletion of cellular GSH. However, again, if the 1mM N-acetylcysteine was supplemented, the rates of losses of GSH and cell viability were retarded in both cases. Even though large amounts of the added N-acetylcysteine was present in the cell, N-acetylcysteine conjugate of acetaminophen was not formed. Instead, only large amounts of GSH conjugate of the drug was produced. Thus, it is concluded that the added N-acetylcysteine is taken up and utilized for resynthesis of GSH. In turn, this resynthesized GSH contributes to the protection against cytotoxicity inducible with hepatotoxic drugs.

• Journal of The Korean Society of Clinical Toxicology
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• v.15 no.2
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• pp.122-130
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• 2017

Purpose: To evaluate the effects of low-dose intravenous N-acetylcysteine on the prevention of contrast-induced nephropathy (CIN) in patients undergoing computed tomography (CT). Methods: All patients presenting to our emergency department and undergoing CT with intravenous contrast media between August 2014 and April 2016 were retrospectively enrolled. We included hospitalized patients with renal dysfunction [estimated glomerular filtration rate (GFR) between 30 and $89mL/min/1.73m^2$]. A 600-mg injection of N-acetylcysteine was given to patients once before and once immediately after CT, depending on the preference of physician. The primary outcome was CIN defined as an increase in creatinine level of ${\geq}25%$ or ${\geq}0.5mg/dL$ from the baseline within 48 to 72 hours after CT. A trained person blindly reviewed all medical records. Results: Of the 1903 admitted patients, CIN occurred in 9.8% of patients who received 1200 mg intravenous N-acetylcysteine (24/244) and 6.8% of patients who did not (113/1659, p=0.090). In a multivariable regression analysis, N-acetylcystine was not relevant to the prevention of CIN (odds ratio=1.42 [95% CI, 0.90-2.26]). Even in the stratified analysis using the propensity score matching, N-acetylcysteine was irrelevant (GFR 30-59: odds ratio=1.06 [95% CI, 0.43-2.60]; GFR 60-89: odds ratio=1.76 [95% CI, 0.75-4.14]). After adjustment, crystalloids were significantly associated with the reduction in CIN compared with dextrose water (odds ratio=0.60 [95% CI, 0.37-0.97]). Conclusion: No effect was found when low-dose intravenous N-acetylcysteine was used to prevent CIN. However, there seems to be an association between crystalloids and reduction in CIN.

• The Korean Journal of Community Living Science
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• v.21 no.1
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• pp.71-79
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• 2010

This study was conducted to develop fresh-cut and processed pears. After treatment of citric acid (1%) or N-acetylcysteine (0.2 M), and co-treatment of citric acid (1%) and N-acetylcysteine (0.2 M) into the pears c.v. 'Wonhwang', the quality changes of pears during cold storage ($1^{\circ}C$) for 10 days were investigated respectively. Pear quality and the taste of pears increased much more in those treated with anti-browning agents than those in the control group at 10 days after anti-browning treatment and cold storage. Changes in Hunter b values of pears treated with 0.2 M N-acetylcysteine were insignificant. Those with Polyphenol oxidase (PPO) activity and ethylene production were had the most decreased effects and those with the phenolics compound contents were the most lowered. Firmness of fruits increased in treatment of 0.2 M N-acetylcysteine + 1% citric acid solution. The amount of respiration decreased in the application of 1% citric acid solution. Consequently, fruit freshness can be maintained more effectively by the treatment of the anti-browning agent compared to non-treatment, even if the effectiveness were different among different kinds of anti-browning agents.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.44 no.5
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• pp.484-489
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• 2011

This study examined whether N-acetylcysteine (NAC), a glutathione precursor, could attenuate toxic effects of three fish anti-parasitic agents, trichlorfon, hydrogen peroxide ($H_2O_2$) and formalin, all of which are known to exert side effects through free radical production. Common carp Cyprinus carpio were fed with NAC (approx. 50 mg/kg/day) for 3 consecutive days prior to anti-parasite bathing for a 24 hr period. Mortality rates were examined during this 24 hr bathing period, and selected hematological and biochemical parameters were also assessed at the termination of anti-parasite exposure. The mortality rates and plasma glucose elevations caused by all three anti-parasitics were significantly reduced by NAC pretreatment. Trichlorfon, but not $H_2O_2$ or formalin, elevated plasma levels of aspartatetransaminase (AST) and alanine-transaminase (ALT), and these elevations were attenuated by NAC. There was no change in hematocrit values in any treatment. The results provide evidence for the attenuating effects of NAC against toxicity caused by anti-parasite agents that act through free radical-producing properties. The results found in this study also suggest that NAC may be administered to fish to minimize toxicity in fish parasiticide use.

• Korean Journal of Veterinary Research
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• v.61 no.2
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• pp.16.1-16.6
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• 2021

Pseudomonas aeruginosa is one of the most common pathogenic species associated with canine otitis externa (OE). Their resilience is achieved by forming a biofilm, which allows these bacteria to evade even the harshest of treatments. This study evaluated the in vitro synergistic efficacy of N-acetylcysteine (NAC) with different antimicrobial agents against P. aeruginosa isolated from dogs with OE to develop an effective treatment against P. aeruginosa. The antimicrobial activity was evaluated by the minimum inhibitory concentration test using the microdilution method. The efficacy of antibiofilm formation was evaluated using a crystal violet stain method. The treatment solutions included NAC alone, and in synergy with enrofloxacin, polymyxin B, and gentamicin. NAC alone exhibited antimicrobial and antibiofilm abilities. On the other hand, the combination of NAC and the antibiotics did not show any significant synergistic effects against P. aeruginosa.

• Preventive Nutrition and Food Science
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• v.14 no.1
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• pp.14-20
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• 2009

Matrix metalloproteinases (MMPs) are a group of zinc proteases that serve the function of breaking down extracellular matrix (ECM). The present study evaluated the role of N-acetylcysteine (NAC) on the increased deposition of ECM in hepatic and glomerular fibrosis caused by carbon tetrachloride ($CCl_4$). The activity of MMPs increased and the levels of tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) decreased in the liver and kidney of $CCl_4$-treated rats. Rats treated with $CCl_4$ and NAC showed increased activities of MMPs and decreased levels of TIMP-1 and TIMP-2 in the liver and kidney. Treatment with NAC resulted in the effective degradation of ECM due to an increase in the activities of MMPs and a decrease in the levels of TIMPs.

• 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.