Therapeutic Effect Of N-acetylcysteine Research Articles

N-acetyl cysteine and zinc sulphate ameliorated crude oil-induced hepatotoxicity in Wistar rats

Even while crude oil offers many advantages, its toxic chemical composition has been shown to negatively interfere with the body's ability to maintain homeostasis. This investigation examined the effects of crude oil on the liver function of Wistar rats as well as the protective effects of N-acetyl cysteine (NAC) and zinc sulphate (ZnSO4). The experimental group and control group consisted of 42 Wistar rats, which were divided into groups of six each. The experimental group had six groups, while the control group only consumed food and water. In the experimental group, three groups received a diet contaminated with crude oil for two, three, and four weeks, respectively. In addition, another three groups received NAC (100 mg/kg), ZnSO4 (0.5 mg/kg), and a combination of NAC and ZnSo4 for three weeks each. Rats' body weights were recorded both before and after the administration of crude oil. Using commercial kits and histological examinations carried out using conventional histopathological methods, the liver's toxicity was assessed. As a result of eating food contaminated with crude oil, the results showed a significant drop (p < 0.05) in body weight. Additionally, there was liver cell injury. The levels of alkaline phosphatase and alanine transaminase considerably increased. Histological analysis revealed abnormal changes to the liver's typical structure. NAC and ZnSO4 therapy reduced the elevated Alanine transaminase and alkaline phosphatase levels. The study's findings highlight the negative impacts of crude oil and the therapeutic effects of NAC and ZnSO4.

N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation.

Hyperlipidemia is a major risk factor for erectile dysfunction (ED). Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) are the key pathological factors of ED. N-acetylcysteine (NAC) can inhibit oxidative stress; however, whether NAC can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear. A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley (SD) rats fed a high-fat and high-cholesterol diet (hyperlipidemic rats, HR). In addition, 9 male SD rats were fed a normal diet to serve as controls (NC). HR rats were divided into three groups: HR, HR+normal saline (NS), and HR+NAC (n = 9 for each group; NS or NAC intraperitoneal injections were administered daily for 16 weeks). Subsequently, the lipid profiles, erectile function, oxidative stress, phenotypic modulation markers of CCSMCs, and tissue histology were analyzed. The experimental results revealed that erectile function was significantly impaired in the HR and HR + NS groups, but enhanced in the HR + NAC group. Abnormal lipid levels, over-activated oxidative stress, and multi-organ lesions observed in the HR and HR + NS groups were improved in the HR + NAC group. Moreover, the HR group showed significant phenotypic modulation of CCSMCs, which was also inhibited by NAC treatment. This report focuses on the therapeutic effect of NAC in restoring erectile function using a hyperlipidemic rat model by preventing CCSMC phenotypic modulation and attenuating oxidative stress.

N-acetylcysteine alleviates oxidative stress and apoptosis and prevents skeletal muscle atrophy in type 1 diabetes mellitus through the NRF2/HO-1 pathway

AimsType 1 diabetes mellitus (T1DM) has been linked to the occurrence of skeletal muscle atrophy. Insulin monotherapy may lead to excessive blood glucose fluctuations. N-acetylcysteine (NAC), a clinically employed antioxidant, possesses cytoprotective, anti-inflammatory, and antioxidant properties. The objective of our study was to evaluate the viability of NAC as a supplementary treatment for T1DM, specifically regarding its therapeutic and preventative impacts on skeletal muscle. Main methodsHere, we used beagles as T1DM model for 120d to explore the mechanism of NRF2/HO-1-mediated skeletal muscle oxidative stress and apoptosis and the therapeutic effects of NAC. Oxidative stress and apoptosis related factors were analyzed by immunohistochemistry, immunofluorescence, western blotting, and RT-qPCR assay. Key findingsThe findings indicated that the co-administration of NAC and insulin led to a reduction in creatine kinase levels, preventing weight loss and skeletal muscle atrophy. Improvement in the reduction of muscle fiber cross-sectional area. The expression of Atrogin-1, MuRF-1 and MyoD1 was downregulated, while Myh2 and MyoG were upregulated. In addition, CAT and GSH-Px levels were increased, MDA levels were decreased, and redox was maintained at a steady state. The decreased of key factors in the NRF2/HO-1 pathway, including NRF2, HO-1, NQO1, and SOD1, while KEAP1 increased. In addition, the apoptosis key factors Caspase-3, Bax, and Bak1 were found to be downregulated, while Bcl-2, Bcl-2/Bax, and CytC were upregulated. SignificanceOur findings demonstrated that NAC and insulin mitigate oxidative stress and apoptosis in T1DM skeletal muscle and prevent skeletal muscle atrophy by activating the NRF2/HO-1 pathway.

N-Acetylcysteine attenuated pulmonary fibrosis induced by bleomycin via immunomodulation responses.

Pulmonary fibrosis (PF) is a chronic and life-threatening interstitial lung disease. N-acetyl cysteine (NAC) is an antioxidant pharmaceutically available to reduce endothelial dysfunction, inflammation, and fibrosis, however, the therapeutic effect of NAC on PF has not been clearly identified. This research aimed to investigate the possible therapeutic impact of NAC on PF induced by bleomycin in the rat model. Rats received intraperitoneal injections of NAC at 150, 300, and 600 mg/kg for 28 days before bleomycin, while the positive and negative control groups were treated with bleomycin alone and normal saline, respectively. Then, rats' lung tissues were isolated and leukocyte infiltration and also collagen deposition were evaluated using hematoxylin and eosin and Mallory trichrome stainings, respectively. In addition, the levels of IL-17, and TGF-β cytokines in bronchoalveolar lavage fluid and hydroxyproline in homogenized lung tissues were assayed using the ELISA method. Histological findings indicated that NAC decreased leukocyte infiltration, collagen deposition, and fibrosis score in the bleomycin-induced PF tissue. Moreover, NAC significantly reduced TGF-β and hydroxyproline levels at 300-600 mg/kg, as well as IL-17 cytokine at 600 mg/kg. NAC showed a potential anti-fibrotic effect by reducing hydroxyproline and TGF-β as well as an anti-inflammatory effect by decreasing IL-17 cytokine. So, it may be administered as a prophylactic or therapeutic candidate agent to attenuate PF via immunomodulatory effects. Although, future studies are suggested.

Principles behind SLE treatment with N-acetylcysteine.

Systemic lupus erythematous (SLE) is a multisystem chronic autoimmune disease in which disrupted molecular pathways lead to multiple clinical manifestations. Currently approved treatments include hydroxychloroquine, some immunosuppressive medications, and some biologics. They all come with a range of side effects. N-acetylcysteine (NAC) is an antioxidant that has shown potential benefits in SLE patients without having major side effects. The following review highlights the molecular mechanisms behind the therapeutic effect of NAC in SLE patients. A higher-than normal mitochondrial transmembrane potential or mitochondrial hyperpolarization (MHP) was found in lymphocytes from SLE patients. MHP is attributed the blocked electron transport, and it is associated with the depletion of ATP and glutathione and the accumulation of oxidative stress-generating mitochondria due to diminished mitophagy. Comprehensive metabolome analyses identified the accumulation of kynurenine as the most predictive metabolic biomarker of lupus over matched healthy subjects. Cysteine is the rate-limiting constituent in the production of reduced glutathione, and it can be replaced by its precursor NAC. Kynurenine accumulation has been reversed by treatment with NAC but not placebo in the setting of a double-blind placebo-controlled clinical trial of 3-month duration. Mitochondrial oxidative stress and its responsiveness to NAC have been linked to systemic inflammation, gut microbiome changes, and organ damage in lupus-prone mice. Given the unique safety of NAC and chronicity of SLE, the clinical trial of longer duration is being pursued.

N-acetylcysteine alleviates fine particulate matter (PM2.5)-induced lung injury by attenuation of ROS-mediated recruitment of neutrophils and Ly6Chigh monocytes and lung inflammation

BackgroundExposure to particulate matter (PM) may contribute to lung inflammation and injury. The therapeutic effect of N-acetylcysteine (NAC), a well-known antioxidant, with regards to the prevention and treatment of fine PM (PM2.5)-induced lung injury is poorly understood. This study aimed to determine the effect of PM2.5 on the recruitment of neutrophils and Ly6Chigh monocytes into lung alveoli and the production of proinflammatory proteins by stimulating the generation of reactive oxygen species (ROS), and to investigate the therapeutic effect of NAC on PM2.5-induced lung injury. MethodsC57BL/6 mice were exposed to a single administration of PM2.5 (200 μg/100 μl/mouse) or phosphate-buffered saline (control) via intratracheal instillation. The mice were injected intratracheally via a microsprayer aerosolizer with NAC (20 or 40 mg/kg) 1 h before PM2.5 instillation and 24 h after PM2.5 instillation. Total protein, VEGF, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF) were measured. Oxidative stress was evaluated by determining levels of malondialdehyde (MDA) and nitrite in BALF. Flow cytometric analysis was used to identify and quantify neutrophils and Ly6Chigh and Ly6Clow monocyte subsets. ResultsNeutrophil count, total protein, and VEGF content in BALF significantly increased after PM2.5 exposure and reached the highest level on day 2. Increased levels of TNF-alpha, IL-6, nitrite, and MDA in BALF were also noted. Flow cytometric analysis showed increased recruitment of neutrophils and Ly6Chigh, but not Ly6Clow monocytes, into lung alveoli. Treatment with NAC via the intratracheal spray significantly attenuated the recruitment of neutrophils and Ly6Chigh monocytes into lung alveoli in PM2.5-treated mice in a dose-dependent manner. Furthermore, NAC significantly attenuated the production of total protein, VEGF, nitrite, and MDA in the mice with PM2.5-induced lung injury in a dose-dependent manner. ConclusionPM2.5-induced lung injury caused by the generation of oxidative stress led to the recruitment of neutrophils and Ly6Chigh monocytes, and production of inflammatory proteins. NAC treatment alleviated PM2.5-induced lung injury by attenuating the ROS-mediated recruitment of neutrophils and Ly6Chigh monocytes and lung inflammation.

N-acetylcysteine as an adjunct treatment of schizophrenia

IntroductionAn increasing body of literature supports the hypothesis that immune imbalance towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this dysregulation, ameliorating the symptoms of schizophrenia. N-acetylcysteine exhibits anti-inflammatory properties and may regulate various neurological pathways, including glutamate dysregulation, oxidative stress, and inflammation, becoming an interesting augmenting drug for schizophrenia treatment.ObjectivesWe aim to review the literature regarding the therapeutic effects of N-acetylcysteine in Schizophrenia.MethodsWe performed an updated review in the PubMed database using the terms “N-acetylcysteine” and “Schizophrenia”. The included articles were selected by title and abstract.ResultsThe literature suggests that N-acetylcysteine may be a useful adjunct to standard treatment for the improvement of schizophrenia symptoms, as well as the cognitive domain of working memory. Also, this augmentation therapy seems to be beneficial in all illness stagesConclusionsN-acetylcysteine appears to be a promising agent for augmenting conventional pharmacotherapy in schizophrenia, however, further research is needed to consolidate the current findings.

N-Acetyl Cysteine Overdose Inducing Hepatic Steatosis and Systemic Inflammation in Both Propacetamol-Induced Hepatotoxic and Normal Mice.

Acetaminophen (APAP) overdose induces acute liver damage and even death. The standard therapeutic dose of N-acetyl cysteine (NAC) cannot be applied to every patient, especially those with high-dose APAP poisoning. There is insufficient evidence to prove that increasing NAC dose can treat patients who failed in standard treatment. This study explores the toxicity of NAC overdose in both APAP poisoning and normal mice. Two inbred mouse strains with different sensitivities to propacetamol-induced hepatotoxicity (PIH) were treated with different NAC doses. NAC therapy decreased PIH by reducing lipid oxidation, protein nitration and inflammation, and increasing glutathione (GSH) levels and antioxidative enzyme activities. However, the therapeutic effects of NAC on PIH were dose-dependent from 125 (N125) to 275 mg/kg (N275). Elevated doses of NAC (400 and 800 mg/kg, N400 and N800) caused additional deaths in both propacetamol-treated and normal mice. N800 treatments significantly decreased hepatic GSH levels and induced inflammatory cytokines and hepatic microvesicular steatosis in both propacetamol-treated and normal mice. Furthermore, both N275 and N400 treatments decreased serum triglyceride (TG) and induced hepatic TG, whereas N800 treatment significantly increased interleukin-6, hepatic TG, and total cholesterol levels. In conclusion, NAC overdose induces hepatic and systemic inflammations and interferes with fatty acid metabolism.

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature.

Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential.

Therapeutic effect of N-acetylcysteine on chemotherapy-induced liver injury.

N-acetylcysteine (NAC) may be useful in the management of chemotherapy-induced liver injury. The present study evaluates the possible therapeutic effects of NAC on chemotherapy-induced hepatotoxicity. A total of 102 patients' files who were diagnosed with cancer between 2015 and 2019 were evaluated retrospectively. Two patient groups with and without NAC were selected. NAC was administered in a 3-μg/kg IV dose in a 24-h infusion to 70 patients when any alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT) values reached three times the normal levels. The other group consisted of 32 patients who were not treated with NAC. Alanine aminotransferase and GGT values were recorded at pretreatment, and on the 1st, 3rd, 5th, and 7th days in both the NAC and non-NAC groups from files. In the NAC group, ALT and GGT values on day 1, 3, 5, and 7 differed from each other, decreasing from day 1 to day 7. A statistically significant difference was noted between the values in the NAC group (p < 0.001). In the non-NAC group, the ALT values on day 7 were lower than the ALT values on day 1. A comparison of the ALT and GGT values in the NAC and non-NAC groups found that the values in the NAC group decreased earlier than in the non-NAC group. This study shows that NAC has a therapeutic effect on hepatotoxicity in children being treated with chemotherapeutic agents due to underlying malign diseases. The early reduction in the results of liver function tests is important for the continuation of chemotherapy.

Therapeutic effects of N-acetylcysteine against malathion-induced hepatotoxicity

BackgroundThe wide unregulated use of malathion has produced severe health hazards. N-acetylcysteine (NAC) is a known glutathione precursor, and there is a growing attention concerning its beneficial effects against pesticide-induced toxicity. The present study was designed to investigate the therapeutic effects of NAC against malathion-induced hepatotoxicity, oxidative stress, genotoxicity, immunotoxicity, inflammation, and acetylcholinestrase alteration in rats. MethodsFour groups comprised of 25 male rats each. Group 1 received distilled water, group 2 received NAC 150 mg/kg/day, group 3 received malathion 50 mg/kg/day, and group 4 received malathion 50 mg/kg/day followed by NAC 150 mg/kg/day for 90 consecutive days. Aspartate transaminase; alanine transaminase; alkaline phosphatase and lactate dehydrogenase; lipid peroxidation; reduced glutathione and total antioxidant capacity; DNA fragmentation; apoptosis and antiapoptosis-related gene expression; leukocyte counts; myeloperoxidase and immunophenotyping of CD4+ and CD8+; interleukin-1β, interleukin-6, and interferon-γ expression; and acetylcholinestrase were assessed.ResultsMalathion administration resulted in significant hepatic injury, immunotoxicity, genotoxicity, oxidative stress injury, inflammation, and significant reduction in acetylcholinestrase activity. Furthermore, malathion showed damaging histopathological effects on liver tissue. NAC treatment significantly attenuated all the previously mentioned biochemical, molecular, and histopathological alterations induced by malathion. ConclusionNAC had therapeutic effects against the detrimental hazards of malathion. Administering NAC to vulnerable risk groups is recommended.

N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder, involving psychiatric, cognitive and motor symptoms, caused by a CAG-repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Oxidative stress and excitotoxicity have previously been implicated in the pathogenesis of HD. We hypothesized that N-acetylcysteine (NAC) may reduce both excitotoxicity and oxidative stress through its actions on glutamate reuptake and antioxidant capacity. The R6/1 transgenic mouse model of HD was used to investigate the effects of NAC on HD pathology. It was found that chronic NAC administration delayed the onset and progression of motor deficits in R6/1 mice, while having an antidepressant-like effect on both R6/1 and wild-type mice. A deficit in the astrocytic glutamate transporter protein, GLT-1, was found in R6/1 mice. However, this deficit was not ameliorated by NAC, implying that the therapeutic effect of NAC is not due to rescue of the GLT-1 deficit and associated glutamate-induced excitotoxicity. Assessment of mitochondrial function in the striatum and cortex revealed that R6/1 mice show reduced mitochondrial respiratory capacity specific to the striatum. This deficit was rescued by chronic treatment with NAC. There was a selective increase in markers of oxidative damage in mitochondria, which was rescued by NAC. In conclusion, NAC is able to delay the onset of motor deficits in the R6/1 model of Huntington's disease and it may do so by ameliorating mitochondrial dysfunction. Thus, NAC shows promise as a potential therapeutic agent in HD. Furthermore, our data suggest that NAC may also have broader antidepressant efficacy.

N-acetylcysteine and intestinal health: a focus on its mechanism of action.

The integrity of the intestinal epithelium ensures its normal physiological function. Consequently, damage to the mucosal epithelium can impair the absorption of nutrients, thereby reducing the growth performance and compromising the health of animals. N-acetylcysteine (NAC) is pharmaceutically available either intravenously, orally, or by inhalation for reducing endothelial dysfunction, inflammation, fibrosis, invasion, cartilage erosion, acetaminophen detoxification, and transplant prolongation. NAC is rapidly metabolized by the small intestine to produce glutathione and can not be detected in animals without supplementation. The physiologic functions and therapeutic effects of NAC are largely associated with maintaining intracellular concentrations of reduced glutathione. Results from recent studies indicate that NAC reduces inflammation, alleviates oxidative stress, improves energy status, and ameliorates tissue damage in the intestine of lipopolysaccharide-challenged piglets. Moreover, dietary supplementation with NAC ameliorates acetic acid-induced colitis in a porcine model. The effects of NAC are associated with some intestinal cell signaling pathways, such as EGFR, TLR4, apoptosis and tight junction signaling. The current review focuses on the protective effects of NAC on intestinal health and the molecular mechanisms of its action.

Protective and therapeutic potency of N-acetyl-cysteine on propionic acid-induced biochemical autistic features in rats

BackgroundThe investigation of the environmental contribution for developmental neurotoxicity is very critical. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations towards identifying either environmental toxicants that cause or drugs that protect from neurotoxicity and may help in treatment of neurodevelopmental disorders.ObjectiveTo study both the protective and therapeutic effects of N-acetyl cysteine on brain intoxication induced by propionic acid (PPA) in rats.MethodsTwenty-eight young male Western Albino rats were enrolled in the present study. They were grouped into four equal groups, each of 7 animals. Group 1: control group, orally received only phosphate buffered saline; Group 2: PPA-treated group, received a neurotoxic dose of of PPA of 250 mg/kg body weight/day for 3 days; Group 3: protective group, received a dose of 50 mg/kg body weight/day N-acetyl-cysteine for one week followed by a similar dose of PPA for 3 days; and Group 4: therapeutic group, treated with the same dose of N-acetyl cysteine after being treated with the toxic dose of PPA. Serotonin, interferon gamma (IFN-γ), and glutathione-s-transferase activity, together with Comet DNA were assayed in the brain tissue of rats in all different groups.ResultsThe obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of serotonin (5HT), increase in IFN-γ and inhibition of glutathione-s-transferase activity as three biomarkers of brain dysfunction. Additionally Comet DNA assay showed remarkably higher tail length, tail DNA % damage and tail moment. N-acetyl-cysteine was effective in counteracting the neurotoxic effects of PPA.ConclusionsThe low dose and the short duration of N-acetyl-cysteine treatment tested in the present study showed much more protective rather than therapeutic effects on PPA-induced neurotoxicity in rats, as there was a remarkable amelioration in the impaired biochemical parameters representing neurochemical, inflammatory, detoxification and DNA damage processes.

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.

N-Acetyl Cysteine Attenuates the Inflammatory Response in Warm Ischemic Pig Lungs

Lungs donated after cardiac death (DCD) may significantly reduce current organ shortage. However, the warm ischemic period following circulatory arrest may enhance ischemia-reperfusion injury (IRI). We investigated the possible therapeutic effect of N-acetyl cysteine (NAC), a potent anti-oxidative agent on IRI in a porcine ex vivo lung reperfusion model. NAC (50 mg/kg) was nebulized to pigs (n = 6/group) prior to sacrifice (NAC-DCD). In DCD-NAC, animals received NAC 15 min after death. Control animals did not receive an aerosol (DCD). Interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-8, lactate dehydrogenase activity and thiobarbituric acid reactive substances were measured and cells were counted in broncho-alveolar lavage from the right lung after a 3-h warm plus 1-h cold ischemic interval. There were no differences in cells between groups, however cell death was lower in NAC-DCD (10.3 +/- 1.5%) and DCD-NAC (7.83 +/- 1.8%) compared to DCD (18.0 +/- 3.8%). IL-1beta levels (111.5 +/- 28.8 pg/mL and 92.2 +/- 51.0 pg/mL versus 250.3 +/- 56.6 pg/mL) and lactate dehydrogenase activity (1258.0 +/- 440.9 U/L and 1606.0 +/- 289.0 U/L versus 2848.0 +/- 760.9 U/L) were significantly lower in NAC-DCD and DCD-NAC compared with DCD, respectively. These postischemic inflammatory markers correlated with functional parameters upon reperfusion of the left lung, reported in a previous study. Administration of NAC prior to or shortly after circulatory arrest results in a marked reduction of inflammation during the warm ischemic phase.

Beneficial Effect of N-Acetylcysteine against Organophosphate Toxicity in Mice

Recent studies showed that oxidative stress could be an important component of the mechanism of organophosphate (OP) compounds toxicity. The aim of present study was to investigate either prophylactic and therapeutic effects of N-acetylcysteine (NAC) against fenthion-induced oxidative stress in mice. Additionally, the effects on survival rates were investigated. Therefore, we determined the changes of the blood levels of glutathione (GSH), malondialdehyde (MDA), nitrite, and nitrate in blood or serum. Additionally, all animals were observed for 6 h and the survival rates were recorded. It was found that fenthion administration increased the levels of MDA, and decreased the levels of GSH, nitrite and nitrate. On the other hand, both prophylactic and therapeutic NAC treatment decreased the levels of MDA, and increased the levels of GSH, nitrite, and nitrate. The results showed that NAC is able to attenuate the fenthion-induced oxidative stress whereby NAC has not only prophylactic but also therapeutic activity in fenthion poisoning. On the other hand, we found that NAC can clearly improve survival rates in mice administered with an acute high dose of fenthion poisoning. In conclusion, NAC can decrease OP-induced oxidative stress and mortality rate, but the exact mechanism of its NAC protective effect needs to be explored further.

N-Acetylcysteine Use in Ischemic Hepatitis

We describe a case of antidepressant-induced ischemic hepatitis that responded to intravenous administration of N-acetylcysteine. Cytoprotection in the setting of ischemic hepatitis may be a therapeutic effect of N-acetylcysteine.

Protective and therapeutic effects of N-acetylcysteine on lung injury in rats with acute necrotizing pancreatitis

目的 探讨急性坏死性胰腺炎(ANP)大鼠肺损伤与肺组织细胞间粘附分子-1(ICAM-1)、肿瘤坏死因子-α(TNF-α)mRNA表达的关系及N-乙酰半胱氨酸(NAC)对肺损伤的作用.方法 26只Wistar大鼠随机分为正常对照、盐水对照、胰腺炎和胰腺炎+ NAC四组.以3.5%牛磺胆酸钠逆行注入胰胆管制作ANP模型,并将NAC(300 mg/kg)于造模后1 h用于ANP模型,造模后12 h取材.采用RT-PCR法检测肺组织ICAM-1及TNF-α mRNA表达,同时观察血脂肪酶、胰腺组织湿/干重比率、肺组织髓过氧化物酶(MPO)及病理改变.结果 ANP有肺组织学损伤改变,同时伴有肺组织ICAM-1、TNF-α mRNA高表达及MPO活力升高.胰腺炎+NAC组与胰腺炎组比较,胰腺湿/干重比率、肺组织ICAM-1、TNF-α mRNA的表达及MPO均降低.肺组织病理损伤程度与ICAM-1、TNF-α mRNA表达及MPO均呈正相关,相关系数分别为0.92、0.68及0.92(P<0.01).肺MPO与ICAM-1、TNF-α mRNA表达也呈正相关,相关系数为0.87及0.77(P<0.01).结论 NAC可能通过抑制肺ICAM-1、TNF-α mRNA的产生及中性粒细胞的聚集,减轻AP所致的肺损伤;对胰腺本身的损伤也可能有一定的保护作用。

Prophylactic but not therapeutic administration of N-acetylcysteine (NAC) decreases the severity of experimental acute pancreatitis

Background: Inflammation and oxidative stress occur in the pancreas during the early stages of acute pancreatitis. NAC is a thiol compound and can act as a direct scavenger of reactive oxygen species leading to decrease the inflammatory process. Aim: To assess the prophylactic as well as the therapeutic effect of NAC on the early course of acute necrotizing pancreatitis in mice. Methods: Acute pancreatitis (AP) was induced through 4 i.p. injections of 50 }ag/kg cerulein. Mice were assigned to receive either, Group 1: NAC given orally during one week + 1000 mg/kg i.p. one hour before AP induction then every 3 hours for 2 doses, or Group 2:1000 mg/kg i.p. one hour before AP induction then every 3 hours, or Group 3:1000 mg/kg i.p. one hour after AP induction then every 3 hours or Group 4: only saline before AP induction. Severity of AP was assessed in terms of Serum amylase/lipase levels, histological changes (edema, inflammation, necrosis), systemic release of TNF-a and IL-6, intrapancreatic levels of TNF-a and IL-6 and pancreatic glutathione content. Results: Prophylactic administration of NAC (Groups 1 and 2) dramatically decreased the severity (histologically and amylase/lipase levels at 3 and 6 hours after induction) of AP as compared to Group 3 (therapeutic administration) and Group 4 (controls) whose severity was similar. Interestingly, no significant difference was found between group 1 and 2 (NAC given orally as pretreatment or not). Prophylactic administration of NAC led to a significant decrease of systemic IL-6 release (TNF-ct not detectable in this model) and of intrapancreatic IL-6 and TNF-ct levels as compared to therapeutic administration or controls (3 and 6 hours after induction). However, this effect was not dose-dependent (300 mg/kg i.p. = 600 mg/kg = 1000 mg/kg). No significant differences in total pancreatic gluthatione content were found in mice treated with NAC before AP induction compared with those in mice treated with NAC after induction or with controls. Conclusions: NAC administered only in a prophylactic protocol limits the severity of cerulein-induced AP in mice despite no change on pancreatic glutathione content. This suggests that oxidative stress occurs very early in the course of AP and probably triggers the inflammatory process through cytokines induction. This approach may substantiate the prophylactic use of NAC in preventing post-ERCP pancreatitis.