Evaluation of 2-week repeated oral dose toxicity of 100 nm zinc oxide nanoparticles in rats / 한국실험동물학회지

The aim of this study was to verify subacute oral dose toxicity of positively charged 100 nm zinc oxide (ZnO(AE100[+])) nanoparticles (NPs) in Sprague-Dawley rats. ZnO(AE100[+]) NPs were administered to rats of each sex by gavage at 0, 500, 1,000, and 2,000 mg/kg/day for 14 days. During the study period, clinical signs, mortality, body weight, food consumption, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. Increased mortality and clinical signs, decreased body weight, feed consumption, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet (PT), and lymphocyte (LYM) and increased white blood cells (WBCs), neutrophils (NEUs), alkaline phosphatase (ALP), and histopathological alterations in the spleen, stomach, and pancreas were observed at 2,000 mg/kg/day. Increased clinical signs, decreased body weight, feed consumption, HB, HCT, MCV, MCH, MCHC, and LYM and increased WBCs, NEUs, ALP, and histopathological alterations in the spleen, stomach, and pancreas were seen at 1,000 mg/kg/day. Increased clinical signs, decreased MCV and MCH and increased histopathological alterations in the stomach and pancreas were found at 500 mg/kg/day. These results suggest that the target organs were the spleen, stomach, and pancreas in rats. The no-observed-adverse-effect level was <500 mg/kg for both sexes.

Effects of Nano-sized Carbon Black on the Lungs of High Fat-diet Induced Overweight Rats

OBJECTIVES: This study was conducted to determine whether nano-sized carbon black exposure results in greater damage in high fat diet-induced overweight rats than normal weight ones and to identify the possible causes of any differences. METHODS: Two groups of Sprague-Dawley rats allocated by body weight (normal and overweight) were exposed to aerosolized nano-sized carbon black for 6 hours a day, 5 days per week over a 4-week period. Differential cell counts, lactate dehydrogenase (LDH) activities and albumin concentrations were measured in bronchoalveolar lavage (BAL) fluid, and histopathological findings in the lungs were evaluated. Tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 were measured in BAL fluid and supernatants of lipopolysaccharide(LPS)-stimulated lymphocyte culture. RESULTS: Rats exposed to high concentrations of nano-sized carbon black showed significantly increased (p<0.05) polymorphonuclear leukocyte number and LDH activity in the BAL fluid from both overweight and normal rats. Mild histopathological changes were observed in normal rats irrespective of carbon black concentrations. However, severe histological scores were found in overweight rats (1.75+/-0.46, 2.25+/-0.46, and 2.88+/-0.35 after low, medium, and high concentration exposures). Proinflammatory cytokine levels of TNF-alpha and IL-6 were significantly higher in the supernatant of LPS-stimulated lymphocytes of overweight rats, whereas there was no significant difference in the BAL fluid between normal and overweight rats. CONCLUSIONS: Inflammation and damage to lungs exposed to nano-sized carbon black was more severe in high fat diet-induced overweight rats compared to normal rats.

Single-Dose Oral Toxicity of Fermented Scutellariae Radix Extract in Rats and Dogs

The aim of this study was to investigate the acute oral toxicity of fermented Scutellariae Radix (JKTMHGu-100) in rats and dogs. JKTM-HGu-100 was orally administered at a dose of 2,000 mg/kg in Sprague-Dawley rats. An escalating single-dose oral toxicity test in beagle dogs was performed at doses of 500, 1000, and 2000 mg/kg with 4-day intervals. Clinical signs, changes in body weight, mortality, and necropsy findings were examined for 2 weeks following oral administration. No toxicological changes related to the test substance nor mortality was observed after administration of a single oral dose of JKTM-HGu-100 in rats or dogs. Therefore, the approximate lethal dose (LD) for oral administration of JKTMHGu-100 in rats was considered to be over 2,000 mg/kg, and the maximum tolerance doses (MTDs) in rats and dogs were also estimated to be over 2,000 mg/kg. These results indicate that JKTM-HGu-100 shows no toxicity in rodents or non-rodents at doses of 2,000 mg/kg or less.

In vivo metabolism of Talosin A, new isoflavonol glycoside from Kitasatospora kifunensis, in rats

The isoflavonol glycoside Talosin A, genistein (GT)-7-alpha-L-6-deoxy talopyranose (GT-Tal), was first isolated from the culture broth of Kitasatospora kifunensis MJM341. The aim of the present study was to evaluate the oral absorption and metabolism of the newly isolated isoflavonol glycoside, GT-Tal compared to genistin (GT-7-O-beta-D-glucopyranoside; GT-Glu). Free GT-Glu and GT-Tal could not be detected prior to enzymatic hydrolysis of the corresponding conjugates in rat plasma. Following oral administration of GT-Tal (15 min), GT-Tal was rapidly absorbed through the gastrointestinal tract and metabolized into GT-Tal conjugates with a mean Cmax of 2.74 microg/mL. GT-Tal was further metabolized to its aglycone, free GT and conjugated GT. After oral administration, GT-Glu was absorbed after being convereted to its aglycone and then further metabolized into its conjugate metabolites (free GT with a mean Cmax of 0.24 mg/mL at 1.25 h; conjugated GT with a mean Cmax of 1.31 mg/mL at 2.00 h). Significant differences in absorption and metabolism of GT-Tal and GT-Glu were observed. GT-Tal was metabolized into its corresponding conjugates or underwent deglycosylation to form GT, whereas GT-Glu was metabolized into its aglycone, GT.

Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and oral administration in pigs

The pharmacokinetics and dosage regimen of norfloxacin-glycine acetate (NFLXGA) was investigated in pigs after a single intravenous (i.v.) or oral (p.o.) administration at a dosage of 7.2 mg/kg body weight. After both i.v. and p.o. administration, plasma drug concentrations were best fitted to an open two-compartment model with a rapid distribution phase. After i.v. administration of NFLXGA, the distribution (t1/2alpha) and elimination half-life (t1/2beta) were 0.36 +/- 0.07 h and 7.42 +/- 3.55 h, respectively. The volume of distribution of NFLXGA at steady state (Vdss) was 4.66 +/- 1.39 l/kg. After p.o. administration of NFLXGA, the maximal absorption concentration (Cmax) was 0.43 +/- 0.06 microgram/ ml at 1.36 +/- 0.39 h (Tmax). The mean absorption (t1/2ka) and elimination half-life (t1/2beta) of NFLXGA were 0.78 +/- 0.27 h and 7.13 +/- 1.41 h, respectively. The mean systemic bioavailability (F) after p.o. administration was 31.10 +/- 15.16%. We suggest that the optimal dosage calculated from the pharmacokinetic parameters is 5.01 mg/kg per day i.v. or 16.12 mg/kg per day p.o.

Plasma Choline Concentration of Some Korean Young Adults and Correlation with Dietary Choline Intake

The purpose of this study is to investigate the concentration of plasma choline of Korean and to clarify the relationship between plasma choline concentration and choline intake. Plasma choline concentration of 30 young adults (15 males, 15 females) aged 20 - 30 years living in Deajeon metropolitan city are analyzed and their dietary choline intake. Choline content of one day meal was directly analyzed with the use of enzymatic method. Plasma choline concentration from more than 12 hr fasting blood was analyzed by using HPLC-MS. Choline intakes of male subjects were in the range of 253.51 - 1724.14 mg and those of female subjects were in the range of 240.85 - 938.06 mg. Mean intakes of choline were 634.53+/-353.68 mg in male subjects and 473.99+/-183.76 mg in female subjects. Plasma choline concentration of total subjects was in the range of 5.08 - 14.01 micro mol/L. Mean plasma choline concentration was 9.19+/-2.05 micro mol/L in male subjects and 8.11+/-1.70 micro mol/L in female subjects. Plasma choline concentration did not show significant correlation with choline intake in male and total subjects, but showed positive correlation with choline intake in female subjects (p<0.05). This result shows that more studies on large scaled samples are needed.

The anti-thrombotic activity of surfactins

Platelet aggregation was inhibited and the density of platelet-rich plasma (PRP) clots was decreased by the preincubation of PRP with surfactins, an acidic lipopeptide of Bacillus subtilis complex BC1212 isolated from soybean paste, in dose-dependent manner. Our findings suggest that surfactins are able to prevent a platelet aggregation leading to an inhibition of additional fibrin clot formation, and to enhance fibrinolysis with facilitated diffusion of fibrinolytic agents.

Determination of Roxithromycin by Liquid Chromatography/Mass Spectrometry after Multiple-Dose Oral Administration in Broilers

A highly sensitive and specific method for the determination of roxithromycin in broiler tissues by LC/MS was developed and validated. A dichloromethane extract of the sample was separated on C18 reversed-phase column with acetonitrile-50 mM ammonium acetate (80:20, v/v) as the mobile phase and analyzed by LC/MS via atmospheric pressure ionization/electrospray ionization interface. The limit of detection and limit of quantitation were 1 ng/g and 5 ng/g. The method has been successfully applied to determine for roxithromycin in various tissues of broilers. Residue concentrations were associated with administered dose. At the termination of treatment, roxithromycin was found in all collected samples for both dose groups. Liver was detected to have the highest residual concentration of roxithromycin. Residue concentrations of roxithromycin were lower than its LOQ in all tissues from both dose groups 10 days after the treatment of roxithromycin mixed with drinking water at a dose rate of 15 mg/L or 60 mg/L to each broiler for 7 days.

Simultaneous Determination of Various Macrolides by Liquid Chromatography/Mass Spectrometry

Macrolides are frequently used in veterinary medicine as therapeutic and preventive agents for various diseases. It is difficult to determine macrolides simultaneously with conventional methods due to their similar structures. A simultaneous analysis for erythromycin, roxithromycin, tiamulin and tylosin with LC/MS has been developed. Separation was performed on C18 reversed phase column. Mobile phase was gradiently flowed with 10 mM ammonium acetate and methanol. The mass spectrometer was run in the positive mode and selective ion monitoring mode. The molecular ions were [M+H]+ form at m/z 837.5 for erythromycin, at m/z 859.5 for roxithromycin, at m/z 494.2 for tiamulin and at m/z 916.7 for tylosin. Limits of detection were in the range from 0.001 to 0.01 microgram/g lower than their MRLs.