Pharmacokinetics of intravenous N-acetylcysteine in pre-term new-born infants

Background: Reactive oxygen species have been considered to play a role in several clinical complications in pre-term infants. The aim of this study was to determine the pharmacokinetics of intravenous N-acetylcysteine in pre-term neonates. This information is needed to evaluate the use of N-acetylcysteine as an antioxidant in this patient group. Methods: N-acetylcysteine was infused intravenously in ten patients (gestational age 24.9–31.0 weeks, weight 500–1384 g) for 24 h (3.4–4.6 mg/kg/h), starting 2.0–11.2 h from birth (study I) and in six patients (gestational age 25.9–29.7 weeks, weight 520–1335 g) for 6 days (0.3–1.3 mg/kg/h), starting at the age of 24 h (study II). Arterial plasma N-acetylcysteine and cyst(e)ine concentrations were determined from timed samples taken during (study I and II) and after (study I) the N-acetylcysteine infusion. Results: In study I, the mean elimination half-life of N-acetylcysteine was 11 h (range 7.8–15.2 h). The mean plasma clearance of N-acetylcysteine was 37 ml/kg/h (range 13–62 ml/kg/h) and the mean volume of distribution was 573 ml/kg (range 167–1010 ml/kg). The plasma clearance and volume of distribution correlated with weight (r = 0.81, P < 0.01, and r = 0.78, P < 0.01, respectively) and with gestational age (r = 0.71, P < 0.05, and r = 0.64, P < 0.05, respectively). In study II, the steady-state concentration of N-acetylcysteine was reached in 2–3 days in five of six patients during a constant infusion. Conclusions: The pharmacokinetics of N-acetylcysteine in pre-term infants depend markedly on weight and gestational age. The elimination of N-acetylcysteine is much slower in pre-term new-borns than in adults. Received: 12 April 1999 / Accepted in revised form: 18 August 1999     

Influence of environmental and genetic factors on variation in human response to DNA damaging agents

Exogenous DNA damaging agents must be considered in the context of endogenous reactive species which have the potential to damage DNA. Although a no-effect level for a DNA-damaging compound may not exist, it may be feasible to define a level where reducing exposure to the compound is no longer the most effective way of reducing human risk. Modifying environmental factors which affect human response to damage may be the better strategy. Although a number of rare human syndromes are associated with a reduced ability to repair DNA damage, it is not clear how wide is the range of genetic variation in repair capacity among normal individuals. Studies with DNA repair-deficient human syndromes indicate that processes other than mutation and DNA repair must be involved in the development of cancer, and these processes may represent new sources of variation in human response to genotoxic agents.     

Responses of antioxidant systems in the hepatocytes of common carp (Cyprinus carpio L.) to the toxicity of microcystin-LR.

The freshwater, bloom-forming cyanobacterium (blue-green alga) Microcystis aeruginosa produces a peptide hepatotoxin, which causes the damage of animal liver. Recently, toxic Microcystis blooms frequently occur in the eutrophic Dianchi Lake (300 km2 and located in the South-Western of China). Microcystin-LR from Microcystis in Dianchi was isolated and purified by high performance liquid chromatography (HPLC) and its toxicity to mouse and fish liver was studied (Li et al., 2001). In this study, six biochemical parameters (reactive oxygen species, glutathione, superoxide dismutase, catalase, glutathione peroxide and glutathione S-transferase) were determined in common carp hepatocytes when the cells were exposed to 10 microg microcystin-LR per litre. The results showed that reactive oxygen species (ROS) contents increased by more than one-time compared with the control after 6 h exposure to the toxin. In contrast, glutathione (GSH) levels in the hepatocytes exposed to microcystin-LR decreased by 47% compared with the control. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxide (GSH-Px) increased significantly after 6 h exposure to microcystin-LR, but glutathione S-transferase (GST) activity showed no difference from the control. These results suggested that the toxicity of microcystin-LR caused the increase of ROS contents and the depletion of GSH in hepatocytes exposed to the toxin and these changes led to oxidant shock in hepatocytes. Increases of SOD, CAT and GSH-Px activities revealed that these three kinds of antioxidant enzymes might play important roles in eliminating the excessive ROS. This paper also examined the possible toxicity mechanism of microcystin-LR on the fish hepatocytes and the results were similar to those with mouse hepatocytes.     

A comparative study of the antioxidant/prooxidant activities of eugenol and isoeugenol with various concentrations and oxidation conditions

Eugenol (compound 1 in Fig. 1, 4-allyl-2-methyoxyphenol) and isoeugenol (compound 2 in Fig. 1, 4-propenyl-2-methoxyphenol), both used as a flavor agent in cosmetic and food products, have both prooxidant and antioxidant activities. Their adverse effects such as allergic and inflammatory reaction may be due to their prooxidant activity. To clarify the mechanisms of their cytotoxicity and the factors affecting their antioxidant/prooxidant activities, we investigated the cytotoxicity, ROS production, and cellular glutathione (GSH) levels induced by eugenol and isoeugenol in a human submandibular cell line. The cytotoxicity (MTT method) of eugenol was 1 order of magnitude lower than that of isoeugenol (CC₅₀: eugenol, 0.395 mM; isoeugenol, 0.0523 mM); and ROS production (CDF staining) was induced significantly by isoeugenol, but not by eugenol. Under treatment with H₂O₂ (100 μM) plus horseradish peroxidase (1 μg/ml) for 30 min or with visible light irradiation for 5 min, eugenol caused biphasic ROS production characterized by enhanced at lower eugenol concentrations (5–10 μM) and decreased at higher concentrations (500 μM). In contrast, isoeugenol enhanced ROS production over a wide range of concentrations (5–500 μM). Isoeugenol at 1000 μM significantly reduced GSH levels compared with eugenol at the same concentration. The high cytotoxicity of isoeugenol may be attributed to its induction of high ROS production and low GSH levels, possibly as a result of benzyl radical formation. In contrast, the cytotoxicity of eugenol is likely to be mediated by ROS-independent mechanisms, possibly involving phenoxyl radicals and/or eugenol quinone methide.     

祁门红茶抗氧化有效成分的研究

祁门红茶有较强的抗芥花子油氧化的活性.从祁门红茶乙酸乙酯部位,使用硅胶柱层析,结合Sephadex LH-20柱层析方法,分离得到了四个抗氧化有效成分,分别为茶黄素(Theaflavin,TF1)、茶黄素A(Theaflavin-3-galate,TF2A)、茶黄素B(Theaflavin-3'-gallate,TF2B)和茶黄素双没食子酸酯(Theaflavin digallate,TF3).     

竹叶抗氧化物急性和亚慢性毒性研究

目的进行竹叶抗氧化物的急性和亚慢性毒性试验,为其食用提供安全性毒理学评价依据.方法设1.00、2.15、4.64和10.0g/kg体重三剂量组,进行急性毒性研究:设1.43、2.87和4.30g/kg体重三个剂量组,进行亚慢性毒性研究.结果竹叶抗氧化物雌、雄性大鼠经口LD50均大于10.0g/kg体重;大鼠90天喂养试验各剂量组各项指标均未见明显毒性反应.结论在本实验条件下,竹叶抗氧化物按急性毒性分类属实际无毒类;按大鼠90天喂养试验结果,其最大无作用剂量为4.30g/kg体重.     

The role of polysaccharide peptide of Ganoderma lucidum as a potent antioxidant against atherosclerosis in high risk and stable angina patients

ObjectivesAntioxidants can reduce oxidative radicals that affect the early phase of atherogenesis, that is endothelial dysfunction. Polysaccharide Peptide (PsP) derived from Ganoderma lucidum has an active substance in the form of β-glucan. Previous studies have proven the PsP of Ganoderma lucidum as an effective antioxidant in atherosclerotic rats and shows no toxicity in animal model. This study aims to prove the effect of PsP as potent antioxidant in high risk and stable angina patients.MethodThis is a clinical trial conducted to 37 high risk and 34 stable angina patients, which were determined based on ESC Stable CAD Guidelines and Framingham risk score, with pre and post test design without control group. The parameters are superoxide dimustase (SOD) and malondialdehyde (MDA) concentration, circulating endothelial cell (CEC) and endothelial progenitor cell (EPC) counts. The patients were given PsP 750 mg/day in 3 divided dose for 90 days. Paired t-test was performed for normally distributed data, and Wilcoxon test for not normally distributed data, and significant level of p ≤ 0,05.ResultsSOD level in high risk patients slightly increased but not statistically significant with p = 0,22. Level of SOD in stable angina group significantly increased with p = 0,001. MDA concentration significantly reduced in high risk and stable angina patients with p = 0.000. CEC significantly reduced both in high risk and stable angina patients, with p = 0.000 in both groups. EPC count significantly reduced in high risk and stable angina with p = 0.000.ConclusionPsP of Ganoderma lucidum is a potent antioxidant against pathogenesis of atherosclerosis in stable angina and high risk patients     

Toxicity assessment of environmental pollutant phenanthrene in clam Venerupis philippinarum using oxidative stress biomarkers

The objective of this study was to assess potential toxic effects of phenanthrene (PHE) on tissues of clam Venerupis philippinarum using parameters of antioxidant defenses and oxidative stress. Antioxidant biomarkers including ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), superoxide dismutase (SOD), and glutathione (GSH), as well as DNA damage and lipid peroxidation (LPO) in gills and digestive glands of V. philippinarum, were analyzed after a 1-, 3-, 6-, 10- and 15-day exposure to seawater containing PHE at concentrations of 2, 10, 50 μg/L. The results showed that the activity of most antioxidant enzymes was induced throughout the exposure period, and different trends were detected with time of exposure. The oxidative stress could be obviously caused in the gills and digestive glands under the experimental conditions. Overall, our results show that digestive glands are more sensitive to marine environmental stressors than gills, and GSH is proposed as potential useful biomarker as it showed good correlation with the target contaminant. This could provide useful information for toxic risk assessment of environmental pollutant PHE.     

Depression in pregnancy is associated with decreased glutathione peroxidase activity in fetal cord blood.

The investigation of fetal cord blood (FCB) during child delivery has created a novel topic in the field of psychiatric research. The umbilical vein receives nutrients and oxygen from the mother’s circulation and transports them to the fetal circulation. Investigating fetal cord blood during delivery is beneficial for understanding the fetal environment. Depression in pregnancy is associated with medical and emotional burdens. In this study, we aimed to investigate glutathione peroxidase (Gpx) and myeloperoxidase (MPO) activity in the FCB of depressed mothers and healthy controls. Our study included 45 depressed mothers and 59 healthy controls. The FCB samples were collected from the umbilical vein during delivery. We found that Gpx levels were significantly decreased in the FCB of depressed mothers than healthy controls, medians were 0.14 U/ml and 0.16 U/ml respectively, Z: −3.567 and p < 0.001. MPO levels were similar in both groups, medians were 1.0 U/L and 1.2 U/L respectively, Z: −1.837 and p:0.066. Depression in pregnancy may be associated with decreased antioxidant levels, and this condition may cause an oxidative load, which may lead to improper brain development. Future studies should be performed in larger samples to clarify our preliminary results.     

Chemical composition,antioxidant activity and hepatoprotective potential of Rourea induta Planch. (Connaraceae) against CCl4-induced liver injury in female rats

ObjectivesThe aim of this study was to evaluate the flavonoid content of an ethanolic leaf extract from the medicinal plant Rourea induta Planch. (RIEE) and to investigate its hepatoprotective potential and in vivo antioxidant effects.MethodsUsing samples from carbon tetrachloride-treated Wistar female rats treated orally with or without RIEE, we evaluated the aspartate aminotransferase, alanine aminotransferase, and total bilirubin levels in plasma; the levels of the hepatic oxidative stress markers catalase, superoxide dismutase, glutathione peroxidase, and reduced glutathione in liver homogenates; and the thiobarbituric acid reactive substance levels. A histopathology study was performed. A quantitative analysis of the RIEE extract was performed using high-performance liquid chromatography to evaluate its flavonoid content.ResultsOral administration of RIEE significantly reduced carbon tetrachloride-induced elevations in the levels of plasma markers of hepatic damage and lipid peroxidation. It also rescued histopathologic alterations observed in the liver and levels of oxidative stress markers.ConclusionsRIEE exhibits antioxidant and hepatoprotective activities in vivo, which may be attributable to its flavonoids composition [hyperin (2), quercetin-3-O-β-xyloside (4), quercetin-3-O-α-arabinofuranoside (5), and quercetin (6)].