Effect Of N-acetylcysteine Administration Research Articles

N-Acetylcysteine Administration Improves the Redox and Functional Gene Expression Levels in Spleen, Mesenteric Lymph Node and Gastrocnemius Muscle in Piglets Infected with Porcine Epidemic Diarrhea Virus.

Our previous study reported that N-acetylcysteine (NAC) administration improved the function of intestinal absorption in piglets infected with porcine epidemic diarrhea virus (PEDV). However, the effects of NAC administration on the functions of other tissues and organs in PEDV-infected piglets have not been reported. In this study, the effects of NAC on the liver, spleen, lung, lymph node, and gastrocnemius muscle in PEDV-infected piglets were investigated. Thirty-two 7-day-old piglets with similar body weights were randomly divided into one of four groups: Control group, NAC group, PEDV group, and PEDV+NAC group (eight replicates per group and one pig per replicate). The trial had a 2 × 2 factorial design consisting of oral administration of 0 or 25 mg/kg body weight NAC and oral administration of 0 or 1.0 × 104.5 TCID50 PEDV. The trial lasted 12 days. All piglets were fed a milk replacer. On days 5-9 of the trial, piglets in the NAC and PEDV + NAC groups were orally administered NAC once a day; piglets in the control and PEDV groups were orally administered the same volume of saline. On day 9 of trial, piglets in the PEDV and PEDV+NAC groups were orally administrated 1.0 × 104.5 TCID50 PEDV, and the piglets in the control and NAC groups were orally administrated the same volume of saline. On day 12 of trial, samples, including of the liver, spleen, lung, lymph node, and gastrocnemius muscle, were collected. PEDV infection significantly increased catalase activity but significantly decreased the mRNA levels of Keap1, Nrf2, HMOX2, IFN-α, MX1, IL-10, TNF-α, S100A12, MMP3, MMP13, TGF-β, and GJA1 in the spleens of piglets. NAC administration ameliorated abnormal changes in measured variables in the spleens of PEDV-infected piglets. In addition, NAC administration also enhanced the antioxidant capacity of the mesenteric lymph nodes and gastrocnemius muscles in PEDV-infected piglets. Collectively, these novel results revealed that NAC administration improved the redox and functional gene expression levels in the spleen, mesenteric lymph nodes, and gastrocnemius muscle in PEDV-infected piglets.

The effects of N-acetylcysteine administration on metabolic status and serum adiponectin levels in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled trial

• NAC administration to patients with MetS improved antioxidative defense system and inflammatory status. • NAC administration to patients with MetS ameliorated glycemic control and serum HDL-cholesterol levels. • NAC prescription may be a new strategy for the amelioration of metabolic parameters in patients with MetS. This study examined the impact of N-acetylcysteine (NAC) administration on metabolic parameters and serum adiponectin levels in individuals with metabolic syndrome (MetS). This randomized clinical trial included 76 people with MetS, aged 25–75 years. Participants were randomly assigned to receive either 1800 mg/day NAC (n = 38) or matched placebo (n = 38) for 12 weeks. Fasting blood samples were collected at the onset and at the end of 12-week intervention to quantify metabolic parameters. NAC significantly reduced fasting plasma glucose (P = 0.02), fasting serum insulin (P = 0.006), insulin resistance index (P = 0.005), and serum C-reactive protein (P = 0.003), and increased serum HDL-cholesterol (P = 0.001) and plasma total glutathione (P < 0.001) versus the placebo group. NAC administration did not alter adiponectin, blood pressure, other lipid indices, malondialdehyde, and total antioxidant capacity. Overall, 1800 mg/day NAC consumption for 12 weeks in MetS subjects had positive impacts on the parameters of glycemic homeostasis, HDL-cholesterol, inflammatory status, and body antioxidative defense system. NAC prescription may be a new strategy for the amelioration of metabolic parameters in individuals with MetS. Clinical Trial Registration: This clinical trial was prospectively registered in the Iranian website for registration of clinical trials ( https://www.irct.ir/trial/44284 ).

Effects of n-acetylcysteine administration as a preventive therapy for contrast-induced nephropathy after percutaneous coronary intervention in the elderly

Background: Contrast-induced nephropathy (CIN) is a common complication in patients undergoing percutaneous coronary intervention (PCI). The Elderly is one of the risk factors for CIN and increase mortality. N-acetylcysteine is recommended as preventive therapy for CIN post PCI due to its antioxidant activity. However, previous studies have shown that the effectiveness of n-acetylcysteine as preventive therapy for CIN is still inconsistent. Objective: The aim of this study was to determine the effect of N-acetylcysteine as preventive therapy for CIN post PCI in the elderly. Method: This study used a retrospective study design. Data collection was carried out at one General Hospital in Jakarta from January until March 2020. The medical records in the 2019 period were used for the population. We included an elderly patient who underwent PCI by purposive sampling technique and obtained 78 samples. Data were analyzed by paired t-test to determine the effect of N-acetylcysteine as preventive therapy for CIN post PCI in the elderly. Results: The characteristic of elderly patients who underwent PCI were dominated by males (66.67%) with a GFR 20%). Overall, there was an increase in average GFR value (2.33±7.90) in elderly who underwent PCI after n-acetylcysteine administration (p=0.011).Conclusion: N-acetylcysteine was effective in preventing the incidence of CIN post PCI in the elderly.Keywords: N-acetylcysteine, preventive therapy, contrast-induced nephropathy (CIN), percutaneous coronary intervention (PCI), elderly IntisariLatar belakang: Contrast Induced Nephropathy (CIN) diketahui sebagai komplikasi yang banyak terjadi pada pasien yang menjalani intervensi koroner perkutan (IKP). Usia lanjut merupakan salah satu faktor resiko terjadinya CIN dan dapat meningkatkan mortalitas. N-asetilsistein direkomendasikan sebagai terapi pencegahan CIN pasca IKP karena dihubungkan dengan aktivitas antioksidannya. Namun dari berbagai penelitian terkait efektivitas N-asetilsistein untuk mencegah CIN masih beragam dan tidak konsisten.Tujuan: Tujuan penelitian ini untuk mengetahui efek N-asetilsistein sebagai terapi pencegahan CIN paska IKP pada lansia.Metode: Penelitian menggunakan rancangan studi retrospektif. Pengambilan data dilakukan di salah satu rumah sakit umum di Jakarta pada bulan Januari – Maret 2020. Sampel yang digunakan adalah data rekam medik pasien periode tahun 2019 yang menjalani IKP dan berusia lanjut. Pengambilan sampel menggunakan teknik purposive sampling, diperoleh 78 sampel yang memenuhi kriteria inklusi dan eksklusi. Data diolah dan dianalisis dengan uji-t berpasangan untuk mengetahui efek N-asestilsistein sebagai terapi pencegahan CIN paska IKP pada lansia.Hasil: Karakteristik pasien lansia yang menjalani IKP didominasi oleh laki-laki (66,67%) dengan nilai LFG 20%. Secara keseluruhan, terjadi peningkatan rata-rata nilai LFG pada lansia yang menjalani IKP setelah pemberian N-asetilsistein sebesar 2,33±7,90 (p=0,011).Kesimpulan: N-asetilsistein efektif dalam mencegah kejadian CIN paska IKP pada lansia.Kata kunci: N-asetilsistein, contrast induced nephropathy (CIN), intervensi koroner perkutan (IKP), lansia

Effect of N-Acetylcysteine Administration on 30-Day Mortality in Critically Ill Patients with Septic Shock Caused by Carbapenem-Resistant Klebsiella pneumoniae and Acinetobacter baumannii: A Retrospective Case-Control Study.

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab) represent important cause of severe infections in intensive care unit (ICU) patients. N-Acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties, showing also in-vitro antibacterial activity. Aim was to evaluate the effect on 30-day mortality of the addition of intravenous NAC to antibiotics in ICU patients with CR-Kp or CR-Ab septic shock. A retrospective, observational case:control study (1:2) in patients with septic shock caused by CR-Kp or CR-Ab hospitalized in two different ICUs was conducted. Cases included patients receiving NAC plus antimicrobials, controls included patients not receiving NAC. Cases and controls were matched for age, SAPS II, causative agent and source of infection. No differences in age, sex, SAPS II score or time to initiate definitive therapy were observed between cases and controls. Pneumonia and bacteremia were the leading infections. Overall, mortality was 48.9% (33.3% vs. 56.7% in cases and controls, p = 0.05). Independent risk factors for mortality were not receiving NAC (p = 0.002) and CR-Ab (p = 0.034) whereas therapy with two in-vitro active antibiotics (p = 0.014) and time to initial definite therapy (p = 0.026) were protective. NAC plus antibiotics might reduce the 30-day mortality rate in ICU patients with CR-Kp and CR-Ab septic shock.

Effect of N-acetylcysteine administration on the expression and activities of antioxidant enzymes and the malondialdehyde level in the blood of lead-exposed workers

We investigated whether treatment with N-acetylcysteine (NAC) reduces oxidative stress intensity and restores the expression and activities of superoxide dismutase (Sod1, SOD), catalase (Cat, CAT) and glutathione peroxidase (Gpx1, GPx) in lead-exposed workers.The exposed population was divided randomly into two groups. Workers in the first group (reference group, n=49) were not administered any drugs, while workers in the second group (n=122) were treated with NAC at three doses for 12 weeks (200mg, 400mg, 800mg/day).NAC administered orally to lead-exposed workers normalized antioxidant enzyme activities in blood cells. Oxidative stress intensity measured as malondialdehyde (MDA) levels in serum, leukocytes and erythrocytes significantly decreased after NAC administration. NAC may be an alternative therapy for chronic lead intoxication.

Effect of N-acetylcysteine administration on homocysteine level and oxidative damage to proteins in lead-exposed workers

Effect of N-acetylcysteine administration on homocysteine level and oxidative damage to proteins in lead-exposed workers

Effect of N-acetylcysteine administration on expression and activities of antioxidant enzymes in the blood of lead-exposed workers

Effect of N-acetylcysteine administration on expression and activities of antioxidant enzymes in the blood of lead-exposed workers

An effective antioxidant drug on prevention of the necrosis of zone of stasis: N-acetylcysteine

The zone of stasis, the encircling area of the zone of coagulation, is a critical area which determines the depth and width of the necrosis in burns. Many agents were proposed to salvage the zone of stasis. Due to the known preventive and therapeutic effects of N-acetylcysteine on hepatotoxicity, nephrotoxicity, pulmonary injury, and multiple organ failure in humans, the effect of N-acetylcysteine on saving the zone of stasis was investigated in this experimental study. The effects of N-acetylcysteine administration via oral or intraperitoneal route was compared in a rat comb-burn model. The extent of burn wounds was evaluated by photography and planimetry in the groups. Additionally, skin samples were obtained to analyze malondialdehyde levels to see the antioxidant effect of N-acetylcysteine. In control group (no treatment), the burn areas went to near total necrosis. In intraperitoneal and oral treatment groups, skin survival occurred in the interspace area of the comb. There was no difference between the groups in terms of MDA concentrations. In conclusion, this study showed us the possible saving effect of N-acetylcysteine on the zone of stasis. N-acetylcysteine may be used in the cases of severe burns, not only for its effects on wound healing but also the systemic effects of the drug.

Mo1918 Sirolimus use is Associated With Increased Risk for Cardiovascular Events Following Liver Transplantation

N-Acetylcysteine (NAC) improves transplant-free survival (TFS) in patients with non-acetaminophen (APAP) acute liver failure (ALF) when administered in early stages of hepatic encephalopathy (HE). The mechanisms of this benefit are unknown. We hypothesized that NAC may improve TFS by ameliorating the surge of pro-inflammatory cytokines leading to the systemic inflammatory response syndrome (SIRS). Objectives. To determine the effects of NAC administration on serum cytokine concentrations, and to relate cytokine concentrations to outcome, progression of HE, and the SIRS in patients with non-APAP-induced ALF. Methods. Serum samples from 90 patients from the randomized, placebo-controlled ALF Study Group NAC Trial were analyzed. Samples from 45 patients in each group were assayed, and serum cytokine concentrations were determined in multiplex SearchLight® ELISA assays by ThermoFisher. Proand anti-inflammatory cytokines representing activation of Th1 (IL2, IFNγ, TNFα), Th2 (IL-4,6,10,13), and Treg (IL-17,23) classes of T-helper cells were chosen for assay. Results. The number of SIRS components on admission was a predictor of 21 day mortality (p=0.02 by ANOVA). Predictors of TFS in univariate analysis included NAC administration (p=0.005), admission bilirubin (p<0.001), INR (p=0.085), grade 1 vs. 2 HE (p<0.02) and higher admission IL-17 concentrations (p=0.02). However, there were no differences in any serum cytokine concentrations or in SIRS in patients treated with NAC vs. placebo. Stepwise multivariable logistic analysis identified each of these factors as independent predictors of TFS (p<0.0001). IL-17 levels were higher in patients with grade 2 vs. 1 HE (p<0.01) and in those who progressed to grade 3/4 HE (p<0.02). Patterns of elevated cytokines were observed, with levels of Th1 cytokines highly related (r=0.75, p<0.0001), and levels of proand anti-inflammatory cytokines also related (eg., IL-6 and IL-10; r=0.48, p<0.001). IL-6 and IL-10 concentrations were both related to number of SIRS on admission (p<0.01 and p<0.001) and inversely related to mean arterial pressure (r=-0.35 and -0.34, respectively; p<0.001 for both). Conclusions. NAC does not improve TFS by ameliorating the surge of pro-inflammatory cytokines in patients with non-APAPinduced ALF. However, specific proand anti-inflammatory cytokine concentrations are associated with outcome, HE grade, and the SIRS. IL-17 may have an important role in HE progression and outcome.

Mo1917 Relationship of Serum Cytokine Concentrations to Outcome, Complications and N-Acetylcysteine Treatment in Patients With Non-Acetaminophen-Induced Acute Liver Failure

N-Acetylcysteine (NAC) improves transplant-free survival (TFS) in patients with non-acetaminophen (APAP) acute liver failure (ALF) when administered in early stages of hepatic encephalopathy (HE). The mechanisms of this benefit are unknown. We hypothesized that NAC may improve TFS by ameliorating the surge of pro-inflammatory cytokines leading to the systemic inflammatory response syndrome (SIRS). Objectives. To determine the effects of NAC administration on serum cytokine concentrations, and to relate cytokine concentrations to outcome, progression of HE, and the SIRS in patients with non-APAP-induced ALF. Methods. Serum samples from 90 patients from the randomized, placebo-controlled ALF Study Group NAC Trial were analyzed. Samples from 45 patients in each group were assayed, and serum cytokine concentrations were determined in multiplex SearchLight® ELISA assays by ThermoFisher. Proand anti-inflammatory cytokines representing activation of Th1 (IL2, IFNγ, TNFα), Th2 (IL-4,6,10,13), and Treg (IL-17,23) classes of T-helper cells were chosen for assay. Results. The number of SIRS components on admission was a predictor of 21 day mortality (p=0.02 by ANOVA). Predictors of TFS in univariate analysis included NAC administration (p=0.005), admission bilirubin (p<0.001), INR (p=0.085), grade 1 vs. 2 HE (p<0.02) and higher admission IL-17 concentrations (p=0.02). However, there were no differences in any serum cytokine concentrations or in SIRS in patients treated with NAC vs. placebo. Stepwise multivariable logistic analysis identified each of these factors as independent predictors of TFS (p<0.0001). IL-17 levels were higher in patients with grade 2 vs. 1 HE (p<0.01) and in those who progressed to grade 3/4 HE (p<0.02). Patterns of elevated cytokines were observed, with levels of Th1 cytokines highly related (r=0.75, p<0.0001), and levels of proand anti-inflammatory cytokines also related (eg., IL-6 and IL-10; r=0.48, p<0.001). IL-6 and IL-10 concentrations were both related to number of SIRS on admission (p<0.01 and p<0.001) and inversely related to mean arterial pressure (r=-0.35 and -0.34, respectively; p<0.001 for both). Conclusions. NAC does not improve TFS by ameliorating the surge of pro-inflammatory cytokines in patients with non-APAPinduced ALF. However, specific proand anti-inflammatory cytokine concentrations are associated with outcome, HE grade, and the SIRS. IL-17 may have an important role in HE progression and outcome.

Effect of N-Acetyl Cysteine administration to the degree of parasitemia and plasma interleukin-12 level of mice infected with plasmodium berghei and treated with artemisinin

Introduction Protection against malaria requires a cell-mediated immune response which is initiated by releasing interleukin-12 (IL-12) from antigen presenting cells (APC). N-Acetyl Cysteine (NAC) is a precursor of glutathione, while glutathione itself increases IL-12 production. Treatment with NAC combined with artemisinin is supposed to increase cellular immunity of mice during Plasmodium berghei infection. The aim of this study was to measure the effects of NAC administration on the degree of parasitemia and plasma IL-12 level in mice infected with P. berghei and treated with artemisinin. Methods The research was done using post-test-control-only design using 5 groups: group A (negative control group), group B (positive control group, or mice infected with P.berghei without therapy), group C ( mice infected by P.berghei and received artemisinin 0.04 mg/g BW for 7 days), group D (mice infected with P.berghei and received artemisinin in combination with NAC 1 mg/g BW for 7 days) and group E (mice infected wirth P.berghei and received artemisinin in combination with NAC 1 mg/g BW for 3 days and tapered into ½ mg/g BW for 4 days). Parasitemia was followed up every two days. Approximately six days post infection or when the degree of parasitemia reached ± 10% therapy was begun. On the 3rd, 5th, and 7th days post therapy, mice from each group were terminated and assayed for plasma IL-12 level (ELISA, Bender Medsystems GmbH, Vienna, cat. BMS6004). Results All mice treated with artemisinin mono-therapy and combined therapy had significantly decreased parasitemia (P=0.000). There was no significant difference (P>0.05) in decreasing parasitemia among treatment groups. The plasma IL-12 level increased significantly in both groups that received the combination of artemisinin and NAC constant dose and tapering dose compared with the group that received artemisinin mono-therapy (p < 0,05). Plasma IL-12p70 level in the combination of artemisinin and NAC tapering dose therapy group was higher than other groups on the 5th and 7th days post therapy. Conclusion The conclusion of this research is that artemisinin mono-therapy decreased parasitemia effectively as well as the combination therapy of artemisinin and NAC. Artemisinin and NAC therapy, constant and tapering dose, increase plasma IL-12p 70 level more than artemisinin mono-therapy does. The highest plasma IL-12p70 level was found in the artemisinin plus NAC tapering dose therapy group with seven days duration of therapy. (Med J Indones 2009; 18: 5-9) Keywords: N-acetyl Cysteine, Parasitemia, Interleukin-12, Plasmodium berghei

Effect of N-Acetylcysteine Administration on Intraoperative Plasma Levels of Interleukin-4 and Interleukin-10 in Liver Transplant Recipients

We investigated whether intraoperative administration of N-acetylcysteine (NAC) in liver transplant recipients ameliorated their inflammatory responses by increasing intraoperative plasma levels of interleukin (IL)-4 and IL-10. This prospective, randomized, double-blind clinical trial included liver transplant recipients randomly assigned to the NAC-treated (n = 25) or the placebo (n = 25) group. The NAC-treated group received 100 mg/kg dissolved in 5% dextrose over 15 minutes during the anhepatic phase, followed by a continuous infusion of 50 mg/kg in 5% dextrose over the next 24 hours, whereas the placebo group received equal amounts of 5% dextrose solution during the same time. Peripheral blood samples were drawn in EDTA-containing tubes after induction of anesthesia (I-1); at 15 minutes into the anhepatic phase (I-2) prior to the administration of NAC or placebo; at 5 minutes before reperfusion (I-3); at 10 minutes after reperfusion (I-4); at 20 minutes after reperfusion (I-5); at 60 minutes after reperfusion (I-6); and at 1 hour after completion of the liver transplantation (I-7). Cytokine levels were determined using a technique which combined enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Plasma IL-4 levels were significantly higher among the NAC-treated group than the placebo group at I-3 ( P = .046) and I-4 ( P = .041). Plasma IL-10 levels showed significant enhancement in the NAC-treated group at 5 minutes before reperfusion (I-3; P = .007). We concluded that intraoperative NAC administration during the anhepatic phase of liver transplantation significantly increased recipient IL-4 plasma levels before and after reperfusion, and IL-10 plasma values before reperfusion (I-3). These enhancements seemed to be associated with a protective effect against reperfusion injury.

Effects of N-acetylcysteine administration in hepatic microcirculation of rats with biliary cirrhosis

Increased intrahepatic resistance (IHR) in cirrhosis is due to fibrosis and hepatic endothelial dysfunction (HED). Besides producing fibrosis, increased reactive oxygen species (ROS) promotes ROS-related nitration of anti-oxidative enzymes in cirrhotic livers. Tyrosine nitration (nitrotyrosilation)-related inactivation of anti-oxidative enzymes is increased in cirrhotic livers. This study investigates effects of N-acetylcysteine (NAC) administrations in bile-duct-ligation (BDL) rats. This study measured portal venous pressure (PVP), IHR, hepatic endothelial function, hepatic levels of anti-oxidants and oxidants, type III procollagen (PIIIP), proteins expression of thromboxane synthase (TXS), nitrotyrosine, manganese superoxide dismutase (MnSOD), and hepatic NOx and thromboxane A(2) (TXA(2)) production in perfusates. The improvement of HED was associated with decreased PVP and IHR, hepatic protein and mRNA levels of PIIIP, protein expression of TXS and nitrotyrosine, oxidants and production of TXA(2) in NAC-treated BDL rat livers. Conversely, hepatic NOx production, anti-oxidants, and protein expression of MnSOD were increased in NAC-treated BDL rat livers. In NAC-treated cirrhotic rats, the decrease in IHR was mainly caused by its anti-oxidative effect-related prevention of hepatic fibrogenesis associated with the decrease of oxidants-related nitrotyrosilation and improvement of HED.

N-acetylcysteine for Prevention of Radiographic Contrast Material–Induced Nephropathy: Is the Intravenous Route Best?

Use of oral N-acetylcysteine for preventing radiographic contrast material-induced nephropathy (RCIN) has become widespread, despite conflicting results from clinical trials and meta-analyses. The variability in study results may reflect differences in baseline risks in study patients, hydration regimens, choice of contrast agent, definition of RCIN, and the oral dosage formulation of N-acetylcysteine used. Injectable N-acetylcysteine recently has become available in the United States. Although oral N-acetylcysteine regimens are typically administered during a 48-hour period, more rapid intravenous administration could offer an important advantage for urgent procedures such as coronary angiography. However, the three published studies in which intravenous N-acetylcysteine protocols were used have produced divergent results, likely because of substantially different dosage regimens. With few intravenous studies available, clinicians may look to more broadly studied oral regimens to estimate equivalent intravenous dosages. In the oral studies, however, a wide range of formulations were used, and the bioavailability of each product was uncertain. In addition, the intravenous route circumvents first-pass metabolism, resulting in less glutathione production, perhaps compromising the antioxidant effects of N-acetylcysteine administration. Overall, little evidence exists that any studied N-acetylcysteine protocol improves clinical outcomes in terms of reducing length of hospital stay, need for dialysis, or mortality. Furthermore, N-acetylcysteine may directly affect serum creatinine level, which all clinical trials to date have used as a primary outcome measure. If oral or intravenous N-acetylcysteine is used with the intention of preventing RCIN, more established preventive measures should not be overlooked, including adequate hydration with isotonic saline, avoidance of potentially nephrotoxic drugs, and use of iso-osmolar radiographic contrast media.

Total N-Acetylcysteine Levels Are Elevated in the Plasma of Patients with Chronic Renal Failure

Previously, we reported the effect of N-acetylcysteine administration on the concentration of total plasma homocysteine in patients with chronic renal failure. Total plasma NAC was determined before and after p.o. administration of NAC as a measure of patient compliance. However, we did not fully describe the method by which the total plasma N-acetylcysteine was measured, and we did not report the levels of total plasma N-acetylcysteine before or after administration of N-acetylcysteine. Total plasma N-acetylcysteine concentration was determined by reducing the sample with sodium borohydride, precipitating the proteins and quantifying N-acetylcysteine using HPLC with electrochemical detection. The mean concentration of total plasma N-acetylcysteine was 4.0 μM ± 2.1 μM in patients with chronic renal failure, which is greater than the level found in healthy subjects. Following administration of 1.2 g of NAC p.o. the average concentration of total plasma N-acetylcysteine was found to be 14.5 μM ± 9.7 μM.

Effect ofN-acetylcysteine administration on cysteine and glutathione contents in liver and kidney and in perfused liver of intact and diethyl maleate-treated rats

Effect ofN-acetyl-L-cysteine (NAC) administration on cysteine and glutathione (GSH) contents in rat liver and kidney was studied using intact and diethyl maleate (DEM)-treated rats and perfused rat liver. Cysteine contents increased rapidly, reaching peak at 10 min after intraperitoneal NAC administration. In liver mitochondria it increased slowly, reaching peak at 60 min. GSH content did not change significantly in these tissues. However, in liver and kidney depleted of GSH with DEM, NAC administration restored GSH contents in 60 and 120 min, respectively. Perfusion with 10 mM NAC resulted in 76% increase in liver cysteine content, but not in GSH content. Liver perfusion of DEM-injected rats with 10 mM NAC restored GSH content by 15%. Present findings indicate that NAC is an effective precursor of cysteine in the intact liver and kidney and in the perfused rat liver, and that NAC stimulated GSH synthesis in GSH-depleted tissues.

Different susceptibility to the development of nitroglycerin tolerance in the arterial and venous circulation in humans. Effects of N-acetylcysteine administration.

Tolerance to the effects of organic nitrates develops rapidly during continuous exposure to these drugs; its main mechanism seems to be an intracellular sulfhydryl group depletion. However, the relative susceptibility to the development of nitroglycerin tolerance of the arterial or venous circulation in humans is still a matter of dispute. Twenty patients with coronary artery disease underwent a continuous 24-hour nitroglycerin infusion followed by a bolus administration of N-acetylcysteine. Forearm blood flow (ml/100 ml/min) and venous volume (ml/100 ml) were measured by strain gauge plethysmography under control conditions, at the end of nitroglycerin titration, after 24-hour infusion, and after N-acetylcysteine; vascular resistance was calculated as mean cuff blood pressure divided by flow. After 24 hours of nitroglycerin infusion, the initial increase in venous volume was reduced 48% (p less than 0.01), whereas the acute effects on vascular resistance were not attenuated in the whole group. N-Acetylcysteine completely restored nitroglycerin venodilator effects in all 10 patients in whom attenuation of the venous effects was observed during the infusion period. The data indicate that the susceptibility to the development of nitrate tolerance in humans is higher in the venous than in the arterial circulation, and that the sulfhydryl group donor N-acetylcysteine is extremely effective in reversing nitroglycerin tolerance in the venous circulation in humans.

WC-28 Theophylline assay by immunoturbidimetry: Rate enhancement through polymer supplementation

The zone of stasis, the encircling area of the zone of coagulation, is a critical area which determines the depth and width of the necrosis in burns. Many agents were proposed to salvage the zone of stasis. Due to the known preventive and therapeutic effects of N-acetylcysteine on hepatotoxicity, nephrotoxicity, pulmonary injury, and multiple organ failure in humans, the effect of N-acetylcysteine on saving the zone of stasis was investigated in this experimental study. The effects of N-acetylcysteine administration via oral or intraperitoneal route was compared in a rat comb-burn model. The extent of burn wounds was evaluated by photography and planimetry in the groups. Additionally, skin samples were obtained to analyze malondialdehyde levels to see the antioxidant effect of N-acetylcysteine. In control group (no treatment), the burn areas went to near total necrosis. In intraperitoneal and oral treatment groups, skin survival occurred in the interspace area of the comb. There was no difference between the groups in terms of MDA concentrations. In conclusion, this study showed us the possible saving effect of N-acetylcysteine on the zone of stasis. N-acetylcysteine may be used in the cases of severe burns, not only for its effects on wound healing but also the systemic effects of the drug.