DNA damage after acute and chronic treatment with malathion in rats

Malathion is an insecticide widely used in agriculture and in public health programs that when used indiscriminately in large amounts can cause environmental pollution and risk to human health. However, it is possible that during the metabolism of malathion, reactive oxygen species can be generated, and malathion may produce oxidative stress in intoxicated rats that can be responsible for alterations in DNA molecules related in some studies. As a result, the present study aimed to investigate the DNA damage of cerebral tissue and peripheral blood in rats after acute and chronic malathion exposure. We used single cell gel electrophoresis (Comet assay) to measure early damage in hippocampus and peripheral blood and the Micronucleus test in total erythrocytes samples. Malathion was administered intraperitoneally once a day for one day (acute) or for 28 days (chronic) protocols (in both protocols, malathion was administered at 25, 50, 100, and 150 mg/kg). Our results showed that malathion (100 and 150 mg/kg) increased the DNA damage index in the peripheral blood and in the hippocampus after both chronic and acute treatment. Malathion increased the frequency of micronuclei only in chronic treatment at 150 mg/kg dose, and induced a cytotoxic dose-dependent decrease in the frequency of polychromatic erythrocytes in the peripheral blood of rats. In conclusion, since malathion increased both the peripheral blood and hippocampus DNA damage index using the Comet assay and increased the frequency of micronuclei in the total peripheral blood, it can be regarded as a potential mutagen/carcinogenic agent.     

Nuclear magnetic resonance (NMR)-based metabolomic studies on urine and serum biochemical profiles after chronic cysteamine supplementation in rats

The purpose of this study was to investigate the effect of chronic cysteamine (CS) supplementation on rat metabolism. Rats received biweekly intragastric administration of either CS-HCl at 250 mg/kg body weight or saline (control) for 4 weeks. The 24 h urine and blood serum samples after the last CS treatment were analyzed by nuclear magnetic resonance (NMR)-based metabolomics, specifically high-resolution (1)H NMR metabolic profiling combined with multivariate statistics. Metabolic effects of CS include decreased serum acetate, trimethylamine-N-oxide, and urine hippurate, together with increased urine dimethylamine, indicating modulation of intestinal microbial metabolism of the rats. A decrease in urine succinate, citric acid, and serum acetoacetate, together with an increase in serum lactate, was also observed, which suggests that CS supplementation results in perturbation of energy metabolism in rats.     

Improvement of obesity phenotype by Chinese sweet leaf tea (Rubus suavissimus) components in high-fat diet-induced obese rats

Drinking an herbal tea to lose weight is a well-liked concept. This study was designed to examine the possible improvement of obesity phenotype by a new tea represented by its purified components, gallic acid, ellagic acid, and rubusoside (GER). Male obese-prone SD rats were given low-fat diet, high-fat diet, or high-fat diet plus GER at the dose of 0.22 g/kg of body weight for 9 weeks. GER significantly reduced body weight gain by 22% compared to the high-fat diet control group with 48% less abdominal fat gain. Food intake was not affected. Blood glucose was lowered in the GER-treated group, whereas serum triglycerides and cholesterol were significantly reduced by 50%. This improved obesity phenotype may be associated with the attenuated expression of vascular endothelial growth factor in preadipocyte 3T3-L1 cells. Although other underlying, possibly multiple, mechanisms behind the improved phenotype are largely unknown, the observed improvement of multiple obesity-related parameters by the new tea warrants further investigations.     

大力推进生态功能保护区建设

生态安全是国家安全和社会稳定的重要组成部分。阐述了我国生态功能保护区建设的重要性及目前存在的主要问题。并阐明生态功能保护区建设的指导思想、基本原则、主要建设任务与实施措施     

Effect of green tea supplementation on insulin sensitivity in Sprague-Dawley rats

Epidemiological observations and laboratory studies have shown that green tea has a variety of health effects, including antitumor, antioxidative, and hypolipidemic activities. The aim of this study was to examine whether it had an effect on glucose tolerance and insulin sensitivity in Sprague-Dawley rats. In experiment 1 (in vivo study), rats were divided into two groups: a control group fed standard chow and deionized distilled water and a "green tea" group fed the same chow diet but with green tea instead of water (0.5 g of lyophilized green tea powder dissolved in 100 mL of deionized distilled water). After 12 weeks of green tea supplementation, the green tea group had lower fasting plasma levels of glucose, insulin, triglyceride, and free fatty acid than the control rats. Insulin-stimulated glucose uptake of, and insulin binding to, adipocytes were significantly increased in the green tea group. In experiment 2 (in vitro study), a tea polyphenol extract was used to determine its effect on insulin activity in vitro. Green tea polyphenols (0.075%) significantly increased basal and insulin-stimulated glucose uptake of adipocytes. Results demonstrated that green tea increases insulin sensitivity in Sprague-Dawley rats and that green tea polyphenol is one of the active components.     

Nutritional effects of enzymatically modified soybean oil with caprylic acid versus physical mixture analogue in obese Zucker rats

Enzymatically modified soybean oil with caprylic acid (SL), a physical mixture of tricaprylin and soybean oil (PHY), and soybean oil as control were fed (20% of diet weight) to female obese Zucker rats. Both lipids (SL and PHY) have similar total fatty acid composition containing 23.4 mol % caprylic acid (C8:0) but have different lipid structures. After 21 days of feeding, the body weight gain was 36.4% in the SL-fed group and 35.2% in the PHY-fed group, respectively; whereas the body weight of the control group increased 41.6%. Significant differences in the respiratory exchange ratio were observed between the SL and PHY groups. However, the contents of glucose, total and high density lipoprotein (HDL) cholesterol, and very low density and low density lipoprotein (VLDL + LDL) cholesterol in serum were not significantly different between the SL- and PHY-fed groups or among the three dietary groups (control, SL, and PHY) (p < 0.05). On the other hand, plasma total cholesterol and plasma triacylglycerol (TAG) were significantly higher in SL- and PHY-fed groups than in the control group. In the liver and inguinal adipocyte TAG, C8:0 was found in the SL-fed group, whereas it was not observed in the liver and inguinal adipocyte TAG of the PHY-fed group, which suggests that positional distribution of C8:0 of the TAG molecule is an important consideration in the metabolism of lipids. This study showed that different positional distribution in TAG molecules lead to different metabolic fates, resulting in the change of fatty acid composition in liver and inguinal adipose TAG in female Zucker rats.     

Dietary supplementation of grape skin extract improves glycemia and inflammation in diet-induced obese mice fed a Western high fat diet

Dietary antioxidants may provide a cost-effective strategy to promote health in obesity by targeting oxidative stress and inflammation. We recently found that the antioxidant-rich grape skin extract (GSE) also exerts a novel anti-hyperglycemic activity. This study investigated whether 3-month GSE supplementation can improve oxidative stress, inflammation, and hyperglycemia associated with a Western diet-induced obesity. Young diet-induced obese (DIO) mice were randomly divided to three treatment groups (n = 12): a standard diet (S group), a Western high fat diet (W group), and the Western diet plus GSE (2.4 g GSE/kg diet, WGSE group). By week 12, DIO mice in the WGSE group gained significantly more weight (24.6 g) than the W (20.2 g) and S groups (11.2 g); the high fat diet groups gained 80% more weight than the standard diet group. Eight of 12 mice in the W group, compared to only 1 of 12 mice in the WGSE group, had fasting blood glucose levels above 140 mg/dL. Mice in the WGSE group also had 21% lower fasting blood glucose and 17.1% lower C-reactive protein levels than mice in the W group (P < 0.05). However, the GSE supplementation did not affect oxidative stress in diet-induced obesity as determined by plasma oxygen radical absorbance capacity, glutathione peroxidase, and liver lipid peroxidation. Collectively, the results indicated a beneficial role of GSE supplementation for improving glycemic control and inflammation in diet-induced obesity.     

Liquid chromatography-mass spectrometry of cis- and all-trans-lycopene in human serum and prostate tissue after dietary supplementation with tomato sauce

Several epidemiological studies suggest a lower incidence of prostate cancer in men who routinely consume tomato products. Tomatoes are the primary dietary source of lycopene, which is among the most potent antioxidants of the carotenoids. Men with clinical stage T1 or T2 prostate adenocarcinoma were recruited (n = 32) and consumed tomato sauce based pasta dishes for 3 weeks (equivalent to 30 mg of lycopene per day) before radical prostectomy. Prostate tissue from needle biopsy just before intervention and prostectomy after supplementation from a subset of 11 subjects was evaluated for both total lycopene and lycopene geometrical isomer ratios. A gradient HPLC system using a C(18) column with UV-vis absorbance detection was used to measure total lycopene. Because the absorbance detector was insufficiently sensitive, HPLC with a C(30) column and positive ion atmospheric pressure chemical ionization mass spectrometric (LC-MS) detection was developed as a new assay to measure the ratio of lycopene cis/trans isomers in these samples. The limit of detection of the LC-MS method was determined to be 0.93 pmol of lycopene on-column, and a linear response was obtained over 3 orders of magnitude. Total lycopene in serum increased 2.0-fold from 35.6 to 69.9 microg/dL (from 0.664 to 1.30 microM) as a result of dietary supplementation with tomato sauce, whereas total lycopene in prostate tissue increased 3.0-fold from 0.196 to 0.582 ng/mg of tissue (from 0.365 to 1.09 pmol/mg). all-trans-Lycopene and at least 14 cis-isomer peaks were detected in prostate tissue and serum. The mean proportion of all-trans-lycopene in prostate tissue was approximately 12.4% of total lycopene before supplementation but increased to 22.7% after dietary intervention with tomato sauce. In serum there was only a 2.8% but statistically significant increase in the proportion of all-trans-lycopene after intervention. These results indicate that short-term supplementation with tomato sauce containing primarily all-trans-lycopene (83% of total lycopene) results in substantial increases in total lycopene in serum and prostate and a substantial increase in all-trans-lycopene in prostate but relatively less in serum.     

52-Week oral gavage chronic toxicity study with ubiquinone in rats with a 4-week recovery

Potential ubiquinone (CoQ10; a natural fermentation product) toxicity was assessed in rats administered CoQ(10) by oral gavage for 1 year at 100, 300, 600, and 1200 mg/(kg day). No adverse changes in mortality, clinical signs, body weight, food consumption, or clinical pathology results occurred. CoQ(10) had elimination half-lives ranging from 10.7 to 15.2 h. At 1200 mg/(kg day), a high incidence of orange, granular, lumenal exudate in nasal turbinates occurred; microscopically, findings similar to those in the turbinates were occasionally observed in small granulomas within lung alveoli. A dose-related increased incidence of vacuolated macrophages (mesenteric lymph nodes) and vacuolated hepatic periportal cells was noted. Neither were associated with tissue damage or organ dysfunction, so they were not considered to be adverse. The nasal turbinate and lung findings were probably secondary to incidental exposure to crystallized test material. Overall, CoQ(10) was well tolerated by male and female rats at dose levels up to 1200 mg/(kg day).     

Effects of soy protein isolate feeding on severe kidney damage in DOCA salt-treated obese Zucker rats

This study assessed the effects of soy protein isolate (SPI) on severe kidney damage in deoxycorticosterone acetate (DOCA) salt-treated obese Zucker rats. These rats underwent heminephrectomy and were fed either casein or SPI diet for 12 weeks. From weeks 8 to 10 of the experiment, kidney damage was induced by biweekly injection of 25 mg/kg DOCA and administration of 0.5% NaCl (w/v) ad libitum. Urinary protein and N-acetyl-β-d-glucosaminidase excretions of SPI rats were much lower than those of casein rats at weeks 1 (p < 0.01) and 2 (p < 0.05) after DOCA treatment. Abnormal mineral excretions induced by DOCA treatment in casein rats were hardly detected in SPI rats. Severe atrophy of tubular epithelium and some flattened/detached renal tubules were also observed in casein rats, but not in SPI rats. These results indicate that consecutive treatment of SPI protects against renal dysfunction, particularly tubulointerstitial nephritis, in DOCA salt-treated obese Zucker rats.     

Effect of dietary omega 3 phosphatidylcholine on obesity-related disorders in obese Otsuka Long-Evans Tokushima fatty rats

Recent reports have shown that dietary phosphatidylcholine (PC) has various beneficial biological effects. Omega 3 polyunsaturated fatty acids (omega3 PUFAs) have also been reported to have lipid-lowering effects in animal models and human studies. In the present study, we investigated the effect of omega3 PUFAs containing PC (omega3-PC) on obesity-related disorders in Otsuka Long-Evans Tokushima fatty (OLETF) rats. Rats were fed semisynthetic diets that contained either 5% corn oil and 2% egg-PC or 5% corn oil and 2% omega3-PC for 4 weeks. During this 4 week feeding of the omega3-PC, the OLEFT rats showed a decrease of omental white adipose tissue weight. In addition, the omega3-PC diet significantly decreased liver weight and hepatic lipid levels in OLETF rats. These changes were attributable to the significant suppression of fatty acid synthase activity and significant enhancement in the activities of carnitine palmitoyltransferase and peroxisomal beta-oxidation. Moreover, the omega3-PC diet reduced serum glucose levels concomitant with the increase of serum adiponectin levels. These results show that compared with egg-PC, omega3-PC can prevent or alleviate obesity-related disorders through the suppression of fatty acid synthesis, enhancement of fatty acid beta-oxidation, and increase of the serum adiponectin level in OLETF rats.     

Changes in plasma lipid and antioxidant activity in rats as a result of naringin and red grapefruit supplementation

The aim of this investigation was to compare the influence of naringin versus red grapefruit juice on plasma lipid levels and plasma antioxidant activity in rats fed cholesterol-containing and cholesterol-free diets. The antioxidant activity of a correlated quantity of red grapefruit juice was higher than that of naringin. Forty-two male Wistar rats were randomly divided into six groups of 7 named control, naringin, grapefruit, Chol, Chol/naringin, and Chol/grapefruit. The rats of the control group were fed basal diet (BD) and 1-2 mL of distilled water. To the BD of the other five groups were added 0.46-0.92 mg of naringin dissolved in 1-2 mL of distilled water (naringin), 1-2 mL of red grapefruit juice (grapefruit), 1% of nonoxidized cholesterol (NOC) and 1-2 mL of distilled water (Chol), 1% of NOC and 0.46-0.92 mg of naringin in 1-2 mL of water (Chol/naringin), and 1% of NOC and 1-2 mL of red grapefruit juice (Chol/grapefruit). After 30 days of different feeding, it was found that diets supplemented with red grapefruit juice and to a lesser degree with naringin improved the plasma lipid levels mainly in rats fed cholesterol and increased the plasma antioxidant activity. In conclusion, naringin is a powerful plasma lipid lowering and plasma antioxidant activity increasing flavonone. However, fresh red grapefruit is preferable than naringin: it more effectively influences plasma lipid levels and plasma antioxidant activity and, therefore, could be used as a valuable supplement for disease-preventing diets.     

温度对有水保活石斑鱼代谢与鱼肉品质的影响

为探讨温度对有水保活珍珠龙胆石斑鱼代谢与肌肉品质的影响,该文对不同温度有水保活珍珠龙胆石斑鱼的存活率、保活前后的水质变化、血液生化指标与肌肉理化性质等进行了测定。将体质量为(503?31)g的石斑鱼暂养48 h后,以平均1~2℃/h的速度程序降温至13~14℃,分别在15,20,25℃的条件下保活。结果显示:珍珠龙胆石斑鱼在15、20和25℃下保活96 h后的存活率分别为100%,75%和17%。低温保活显著降低水体中代谢产物含量,15组与25℃组相比,珍珠龙胆石斑鱼在24~96 h内的总氨氮产量降低量在38.12%~57.76%。表明低温通过降低鱼体的呼吸代谢,减少水体中总氨氮与非离子氨氮的浓度而减缓水质恶化。休眠后鱼体受到低温应激作用血清皮质醇与血糖水平均显著上升(P0.05)。保活72 h后,与25℃组相比,15℃处理组鱼体血清皮质醇含量显著降低,但血糖水平显著增加(P0.05),表明低温能降低鱼体在保活过程中的应激反应,同时出现显著的高血糖症状。与新鲜的珍珠龙胆石斑鱼相比,保活72 h后,15℃处理组血清中谷丙转氨酶、谷草转氨酶和肌酸激酶活性均无显著性变化(P0.05),乳酸脱氢酶活性、尿素氮、尿酸、总蛋白含量均显著上升(P0.05);而甘油三酯含量显著下降(P0.05);且肌肉中糖原与粗脂肪质量分数分别下降32.50%和36.32%,水分、粗蛋白、乳酸含量、以及持水力和p H值均无显著变化(P0.05),总体优于25℃处理组。表明25℃保活条件下珍珠龙胆石斑鱼通过增强机体代谢酶活性,增加能量物质代谢,而导致肌肉品质下降;而在15℃保活鱼体能维持较低的代谢水平,生存能力提高,保活72 h后肌肉品质无显著变化。因此15℃适合珍珠龙胆石斑鱼的长途保活运输。该研究结果为珍珠龙胆石斑鱼的有水保活运输提供参考。     

Stereospecific analysis of phospholipid classes in skeletal muscle from rats fed different fat sources

The fatty acid (FA) and dimethylacetal profiles of the sn-1 and sn-2 positions of different phospholipid (PL) classes from skeletal muscle of rats as affected by dietary FA profiles were studied. Rats were fed either a control diet, an olive oil-enriched diet, or a sunflower oil-enriched diet. The FA composition of both positions of the studied PL classes was affected by diet to different extents. The FA composition of the sn-2 position of phosphatidylserine was the most influenced by diet, while phosphatidylinositol was less affected by dietary modification. The FA profile of phosphatidylcholine reflected consumed FA better than any other studied PL. Thus, olive oil rats showed higher oleic acid (C18:1 n-9) contents in both positions of phosphatidylcholine, and sunflower oil rats had higher proportions of arachidonic acid (C20:4 n-6) in the sn-1 position of this PL class. Dimethylacetals were scarcely affected by diet, and only the dimethylacetal composition of phosphatidylethanolamine showed significant modifications.     

Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic Acid, an important metabolite of proanthocyanidins in humans

Grape seed extract provides a concentrated source of polyphenols, most of which are proanthocyanidins. Polymeric proanthocyanidins are poorly absorbed in the small intestine of humans, and exposure may result from metabolism to phenolic acids by colonic bacteria. Any biological effects of proanthocyanidins may be due to the phenolic acid metabolites. Several phenolic acids have been identified as proanthocyanidin metabolites, but these may be derived from a range of other dietary sources. The aim of this study was to determine if 24-h urinary excretion of specific phenolic acids increased significantly and consistently following regular supplementation with grape seed extract. In a randomized, double-blind placebo-controlled trial, 69 volunteers received grape seed extract (1000 mg/day total polyphenols) or placebo for 6 weeks. Supplementation with grape seed polyphenols resulted in a consistent increase in the excretion of 3-hydroxyphenylpropionic acid (3-HPP, P < 0.001) and 4-O-methylgallic acid (P < 0.001) and a less consistent increase in the excretion of 3-hydroxyphenylacetic acid (P = 0.002). The observed increase in 3-HPP is in line with the suggestion that this compound is a major phenolic acid breakdown product of proanthocyanidin metabolism in vivo.     

Robust two-stage approach to repeated measurements analysis of chronic ozone exposure in rats

A robust two-stage approach is used to reanalyze the repeated measurements from an experiment of airway responsiveness in rats randomized to long-term exposure at four ozone doses. The concentration-response data generated for each rat may be represented as a hierarchical nonlinear model encompasing the sources of variation within and between individual profile for each rat, the conditional modeling approach can assess the adequacy of an assumed mean model, a fundamental advantage not intrinsic to marginal techniques. The two-stage population inference is based on the estimated individual parameters, thus maintaining an intuitive appeal to the toxicologists who traditionally have fitted a separate curve for each animal and then applied ANOVA to the summary statistics. However, we formally adjust the standard errors for the extra variability due to the initial estimation of the individual parameters and also allow for their within-rat correlation. The robust two-stage method appropriately down weights the a berrant responses arising sporadically within individualsand, more importantly, the rats which may be outlying relative to the usual population variation. The true effect of chronic ozone exposure, including a significant gender interaction, may be masked by a few rats which exert undue influence on the population estimates in a nonrobust analysis.     

Influence of dietary fat and vitamin E supplementation on free radical production and on lipid and protein oxidation in turkey muscle extracts

The objectives of this study were to investigate the effects of dietary fat (6% soy oil or rapeseed oil or tallow) and alpha-tocopheryl acetate supplementation at two levels (30 or 200 ppm) on radical production, measured by ESR spectroscopy, and on lipid and protein oxidation in turkey muscle extracts oxidized by an enzymic system (NADPH, ADP, FeSO(4)/cytochrome P450 reductase). Two muscles were tested: pectoralis major (glycolytic) and sartorius (oxidative) muscles. Radical production measured by ESR was higher in pectoralis major muscle than in sartorius muscle, whereas lipid and protein oxidation was more important in sartorius muscle, showing the importance of the pro-/antioxidant ratio in oxidative processes in muscular cells and of the measurement methodology to appreciate the free radical production. Dietary fat had no effect on the level of ESR signals, whereas feeding of animals with soy oil induced higher oxidation of lipids. Protein oxidation was less sensitive to the nature of the dietary fat than lipid oxidation. Vitamin E supplementation significantly decreased radical production, as measured by ESR spectroscopy. Vitamin E also decreased lipid and protein oxidation, but the effect of vitamin E on protein oxidation was less pronounced than on lipid oxidation.     

Absorption and bioavailability of artepillin C in rats after oral administration

Artepillin C (AC), an active ingredient of Brazilian propolis, permeates intact across Caco-2 cells by transcellular passive diffusion. The permeation of AC across Caco-2 cells is as efficient as that of phenolic acids and the microbial metabolites of poorly absorbed polyphenols, which are actively absorbed by the monocarboxylic acid transporter (MCT) (Biochim. Biophys. Acta 2005, 1713, 138-144). Here, the absorption of orally administered AC in rats has been studied to evaluate its pharmacokinetics and bioavailability in vivo in comparison with those of p-coumaric acid (CA), a substrate of MCT. Rats were given 100 micromol/kg of body weight of AC or CA, and blood was subsequently collected from the portal vein and abdominal artery. AC, CA, and their metabolites were quantified by coulometric detection using HPLC-ECD. The serum concentration of intact AC and CA in the portal vein peaked at 5-10 min after administration, with a C(max) of 19.7 micromol/L for AC and 74.8 micromol/L for CA. The area under the curve (AUC) for intact AC and CA in the portal vein was calculated from the serum concentration as 182.6 and 3057.3 micromol.min.L(-1), respectively. The absorption efficiency of CA was about 17-fold higher than that of AC. Furthermore, the bioavailability of CA was about 278-fold higher than that of AC, and the ratio of AUC in the abdominal artery to AUC in the portal vein was 0.04 and 0.70, for AC and CA, respectively. Thus, AC is likely to be more susceptible to hepatic elimination than is CA. The bioactive compound of AC in vivo should be investigated further.     

Induction of resistance to gray mold with benzothiadiazole modifies amino acid profile and increases proanthocyanidins in grape: primary versus secondary metabolism

Field treatments of grapevine (cv. Merlot) with the plant activator benzothiadiazole (BTH, 0.3 mM) induced resistance against gray mold caused by Botrytis cinerea. Both incidence and severity of the disease were reduced. The resistance was associated with an increase of total polyphenols in berry skins, in particular, the proanthocyanidin fraction, that increased up to 36%. The amino acid profile of leaves was also modified by treatments, particularly lysine, that augmented 4-fold. Other amino acids involved in resistance mechanisms to either biotic or abiotic stress increased as well. These results indicate that BTH treatments can be used to control gray mold, thereby limiting an excessive use of fungicides, and could be exploited to increase the content of micronutrients of high nutritional value, arising from both primary and secondary metabolisms.