Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.
Acetylcysteine ; pharmacology ; Administration, Intranasal ; Animals ; Biological Availability ; Brain ; Brain Chemistry ; Chromatography, Liquid ; Curcumin ; pharmacokinetics ; Rats ; Tandem Mass Spectrometry ; Tissue Distribution

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.
Acetaminophen ; Acetylcysteine ; Administration, Intravenous ; Emergencies ; Humans ; Incidence ; Liver Failure ; Oligopeptides ; Renal Insufficiency ; Retrospective Studies

OBJECTIVETo explore the effects of high-dose N-acetylcysteine on the lung tissues of rats exposed to silica.

METHODSNinety-six Wistar rats were randomly divided into model group, intervention group and control group (32 rats for each group). The rats of model group and intervention group were exposed to silica by intratracheal infusion of silica dust suspension. The rats in the intervention group were orally given high dose N-acetylcysteine. In 3, 7, 14, 28 days after exposure, eight rats in each group were sacrificed, respectively and the lung samples were collected. The pathological changes of lung were evaluated by HE and Masson staining methods. The levels of TNF-alpha and IL-8 in the BALF were detected by ELISA.

RESULTSCompared with the control group, the alveolitis and pulmonary fibrosis in the intervention group were significantly reduced. In 3, 7, 14, 28 days after exposure, the lung/body coefficients in the intervention group were 9.30 +/- 0.78, 6.29 +/- 0.74, 7.63 +/- 0.88, 6.06 +/- 1.16 respectively, which were significantly lower than those (13.84 +/- 1.61, 9.23 +/- 0.87, 11.23 +/- 1.25, 9.56 +/- 0.76, P < 0.01 ) in the model group (P < 0.01). At the different time points, the levels of TNF-alpha and IL-8 in the BALF in the intervention group were significantly higher than those in the control group (P < 0.01), but were significantly lower than those in the model group (P < 0.01).

CONCLUSIONThe intervention with high dose N-acetylcysteine can significantly reduce the alveolitis and the TNF-alpha and IL-8 levels in the BALF, therefore, inhibit and delay the development of pulmonary fibrosis of rats exposed to silicon dioxide.

Acetylcysteine ; administration & dosage ; pharmacology ; Animals ; Bronchoalveolar Lavage Fluid ; Dose-Response Relationship, Drug ; Dust ; Interleukin-8 ; metabolism ; Lung ; drug effects ; pathology ; Male ; Pulmonary Fibrosis ; chemically induced ; metabolism ; Rats ; Rats, Wistar ; Silicon Dioxide ; adverse effects ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVE: To evaluate the protective effects of oral administration of N-acetyl-cysteine (NAC) on noise-induced hearing loss. METHOD: Three hundred sixty three volunteers were recruited and randomly divided into two groups: experimental group (n=223) and control group (n=140). The subjects had received oral administration of NAC in the experimental group and placebo in the control group before noise exposure. The routine audiometric evaluation and ABR testing were performed and recorded pre- and post-noise exposure. The statistical analysis was carried out on the data obtained from two groups with SPSS 11.0. RESULT: The hearings of all the participatory were changed after noise exposure, but there were statistically significant differences between two groups. CONCLUSION The protective effects of NAC were prominent on the noise-induced hearing loss.
Acetylcysteine ; administration & dosage ; therapeutic use ; Adult ; Hearing Loss, Noise-Induced ; drug therapy ; prevention & control ; Humans ; Male ; Military Personnel ; Young Adult

BACKGROUND AND OBJECTIVEHirsutanol A is a novel sesquiterpene compound purified from fungus chondrostereum sp in Sarcophyton tortuosum. Its pharmacologic effect has not been reported yet. This study aimed to investigate cytotoxic effect of Hirsutanol A on hepatocellular carcinoma (HCC) cells and its mechanism.

METHODSHep3B cells were treated with different concentrations of Hirsutanol A. Cell proliferation was detected by MTT assay. The protein expression of LC3 was determined by Western blot. The generation of reactive oxygen species (ROS) was monitored by flow cytometry.

RESULTSHirsutanol A significantly inhibited proliferation of Hep3B cells with 50% inhibition concentrations (IC50) of 14.54, 6.71, and 3.59 micromol/L when exposed to Hirsutanol A for 24, 48, and 72 h, respectively. Incubation of Hep3B cells with Hirsutanol A markedly increased the level of ROS and the autophagy marker MAP-LC3 conversion from type I to type II. Pre-incubation with an antioxidant N-acetyl cystein (NAC) decreased the level of ROS, and reduced MAP-LC3 I-II conversion, and suppressed cell death. Blocking autophagy with a specific autophagy inhibitor 3-methyladenine (3-MA), the cytotoxic effect of this compound was attenuated.

CONCLUSIONHirsutanol A has potent cytotoxic effect, and can induce autophagic cell death via increasing ROS production.

Acetylcysteine ; pharmacology ; Adenine ; analogs & derivatives ; pharmacology ; Agaricales ; chemistry ; Antineoplastic Agents ; administration & dosage ; isolation & purification ; pharmacology ; Autophagy ; drug effects ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Death ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Free Radical Scavengers ; pharmacology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Microtubule-Associated Proteins ; metabolism ; Reactive Oxygen Species ; metabolism ; Sesquiterpenes ; administration & dosage ; isolation & purification ; pharmacology

OBJECTIVETo observe the urinary S-phenylmercapturic acid (S-PMA) variation in the benzene dynamic exposed rat models and benzene exposed workers, and study the feasibility of use of urinary S-PMA as the biomarker in benzene exposed.

METHODSIn an animal model study, forty-eight adult Wistar rats were randomly divided into 4 groups: the control group, low-dose group, middle-dose group and high-dose group. The exposed groups were dynamically exposed for 28 days (4 periods) by benzene and the concentration was monitored. The urine was immediately collected after every exposure period and detected by the liquid chromatographic/mass spectrometry methods. In a cohort study, eighty benzene exposed workers in a ship-yard in Guangzhou were selected as the exposed subjects while forty healthy officers in the same shipyard who were not occupationally exposed to benzene were treated as the control. The urine was collected after work shift. The urinary S-PMA and the benzene in the workplace was treated as the rat model.

RESULTSIn the animal model study, the urinary S-PMA increased along with the environment benzene in every period and had significantly difference in the different exposed groups (P < 0.01 or P < 0.05), but did not change along with the exposed time course (P > 0.05). In the cohort study, the urinary S-PMA in the high-dose group [(27.2 +/- 7.9)microg/L] was significantly higher than the low-dose group [(13.6 +/- 3.4)microg/L] (P < 0.01). Otherwise, the background of urinary S-PMA was lower than 5microg/L in both workers and rat models.

CONCLUSIONThe urinary S-PMA can be proposed as a sensitive biomarker of occupational benzene exposure.

Acetylcysteine ; analogs & derivatives ; urine ; Adult ; Animals ; Benzene ; administration & dosage ; toxicity ; Environmental Exposure ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Rats ; Rats, Wistar ; Young Adult

OBJECTIVETo investigate the effect of N-acetyl-l-cysteine (NAC) on islet beta cell function in hyperlipidemic rats and its mechanism.

METHODSFifty-nine male SD rats of 8 week old were randomly divided into 3 groups: normal diet group(NC, n=20), high fat diet group (HF, n=20) and NAC treated group (NAC, n=19, NAC 300 mg x kg(-1) x d(-1) and high fat diet). At the end of 20 weeks, fasting serum insulin (Ins), glucose(Glu), malonaldehyde (MDA) and reduced glutathione (GSH) were determined in plasma and pancreas tissue. The glucose infusion rate (GIR) was measured by euglycemic hyperinsulinemia clamp to evaluate the peripheral insulin resistance.Pancreatic islets were isolated and subjected to a perifusion medium containing 3.3 mmol/L glucose for 15 min, followed by 16.7 mmol/L glucose for 30 min, insulin content of perifusion medium was measured by RIA. The expressions of IRS-1, IRS-2, Glut-2 gene in islets were detected by real time PCR.

RESULTS(1)The insulin, glucose and MDA concentration in HF group were higher than those in NC group, but GSH levels in plasma and pancreas were lower. NAC intervention could reverse these effects. (2)The GIR was decreased significantly in HF group compared with NC group [(5.25 +/-1.2) Compared with (13.56 +/-1.7) mg x min(-1) x kg(-1), P<0.01], NAC intervention reversed these effect: GIR[(9.28 +/-1.50) Compared with (5.25 +/-1.2)mg x min(-1) x kg(-1), P<0.01]. (3) 16.7 mmol/L glucose increased the insulin secretion in the islet cells of the three groups, but the peak was lower in HF group. NAC intervention reversed these effects. (4) The gene expression of IRS-1 was significantly decreased by 42.3 % in HF group (P<0.05), and the expressions of IRS-2 and Glut-2 were decreased by 28.1% and 22.9% (P<0.05) compared with NC group. In contrast, the expressions of IRS-1, IRS-2, Glut-2 in NAC group increased by 40.2%, 30.2% and 19.1%, respectively than those in HF group.

CONCLUSIONNAC can reverse functional disorder of islet beta cells induced by high-fat-diet feeding. This antioxidant effect might be associated with upgrading gene expression of insulin signal transduction molecules in islet beta cells.

Acetylcysteine ; pharmacology ; Animals ; Dietary Fats ; administration & dosage ; Free Radical Scavengers ; pharmacology ; Hyperlipidemias ; metabolism ; physiopathology ; Insulin Resistance ; Islets of Langerhans ; drug effects ; secretion ; Male ; Oxidative Stress ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects

Acetaminophen ; administration & dosage ; poisoning ; Acetylcysteine ; administration & dosage ; pharmacology ; therapeutic use ; Brunei ; Drug Overdose ; drug therapy ; physiopathology ; Humans

INTRODUCTIONParacetamol overdose is the most common drug overdose worldwide. To our knowledge, the maximum number of paracetamol tablets ingested reported in the literature is 45 g.

CLINICAL PICTUREWe describe a 21-year-old patient who acutely ingested 120 tablets, each 500 mg paracetamol (i.e., 60 g equivalent to 1200 mg/kg body weight) in a suicidal attempt. Our patient also drank 2 bottles of codeine-based cough syrup equivalent to 360 mg of codeine. At 6 hours post ingestion, her serum paracetamol level was 207 mg/L. The poor prognostic factors for paracetamol overdose in our patient included massive paracetamol ingestion (confirmed by blood levels), codeine co-ingestion and elevated serum amylase (189 U/L).

TREATMENTShe was treated with a 3-day modified regimen of intravenous N-acetylcysteine.

OUTCOMEThe liver function tests and the prothrombin time remained normal over the second and third day of admission and the patient was discharged without complications on the fifth day.

CONCLUSIONFrom this experience we feel that in very severe paracetamol poisoning, a modified regime of intravenous N- acetylcysteine for 3 days is safe and efficacious.

Acetaminophen ; blood ; poisoning ; Acetylcysteine ; administration & dosage ; Adult ; Amylases ; blood ; Antidotes ; administration & dosage ; Codeine ; poisoning ; Drug Overdose ; Female ; Humans ; Liver Function Tests ; Narcotics ; poisoning ; Suicide, Attempted ; Tablets ; Time Factors

BACKGROUND AND OBJECTIVES: Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality in coronary angiography. Although the mechanism is unclear, N-acetylcysteine (NAC) is known to protect against CIN. Preliminary studies with NAC have found conflicting results for the prevention of CIN in patients undergoing coronary angiography. This study was designed to evaluate the efficacy and safety of NAC for the prevention of CIN in patients undergoing coronary angiography. SUBJECTS AND METHODS: 48 patients with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration, 2.06+/-0.56 mg/dL), who were undergoing coronary angiography with a nonionic, low-osmolar contrast agent, were prospectively studied. Patients were randomly assigned to receive either the antioxidant, NAC (600 mg orally twice daily), and 0.45% saline intravenously (n=25), before and after administration of contrast agents, or saline only (n=23). The renal function parameters were assessed 48 hour before and after radiocontrast media administration. RESULTS: 14 of the 48 patients (29%) showed an increase in the 0.5 mg/dL serum creatinine concentration after 48 hours of contrast media administration: 4 of the 25 patients in the NAC group (16%) and 10 of the 23 in the control group (43%; p=0.036; relative risk, 0.37; 95% confidence interval, 1.04 to 7.79). In the NAC group, the mean serum creatinine concentration insignificantly increased (p=0.54), from 2.2+/-0.8 to 2.3+/-0.9 mg/dL, after 48 hours of contrast media administration; whereas, in the control group, the mean serum creatinine concentration significantly increased (p=0.011), from 1.9+/-0.4 to 2.2+/-0.8 mg/dL. The absolute change in serum creatinine concentration was significantly greater in the control than the NAC group (p=0.044). CONCLUSION: Prophylactic oral administration of the antioxidant NAC, along with hydration, prevents the decrease in the renal function induced by a nonionic, low-osmolality contrast agent in patients with chronic renal insufficiency.
Acetylcysteine* ; Administration, Oral ; Contrast Media ; Coronary Angiography* ; Creatinine ; Humans ; Mortality ; Prospective Studies ; Renal Insufficiency, Chronic