Blood Glucose ; Humans ; Hydrocarbons, Brominated ; toxicity ; Occupational Exposure ; adverse effects

The production of water-soluble pigments by fungal strains indigenous to South Korea was investigated to find those that are highly productive in submerged culture. Among 113 candidates, 34 strains that colored the inoculated potato dextrose agar medium were selected. They were cultured in potato dextrose broth and extracted with ethanol. The productivity, functionality (radical-scavenging activities), and color information (CIELAB values) of the pigment extracts were measured. Five species produced intense yellowish pigments, and two produced intense reddish pigments that ranked the highest in terms of absorbance units produced per day. The pigment extracts of Penicillium miczynskii, Sanghuangporus baumii, Trichoderma sp. 1, and Trichoderma afroharzianum exhibited high radical-scavenging activity. However, the S. baumii extract showed moderate toxicity in the acute toxicity test, which limits the industrial application of this pigment. In conclusion, P. miczynskii KUC1721, Trichoderma sp. 1 KUC1716, and T. afroharzianum KUC21213 were the best fungal candidates to be industrial producers of safe, functional water-soluble pigments.
Agar ; Colorimetry ; Efficiency ; Ethanol ; Fungi* ; Glucose ; Korea ; Penicillium ; Solanum tuberosum ; Toxicity Tests, Acute ; Trichoderma

OBJECTIVEMyriocin (ISP-1) is a new type of immune inhibitor extracted from cordyceps sinensis. This study was to observe the effects of ISP-1 on the expression of cell cycle regulatory protein D1 (cyclinD1) in high glucose-induced hypertrophy rat glomerular mesangial cells (GMCs).

METHODSRat GMCs were cultured in vitro and divided into three groups: high glucose (450 mg/dL D-glucose), normal glucose (100 mg/dL D-glucose, control) and ISP-1 (450 mg/dL D-glucose plus 100 μg/mL ISP-1). The protein expression of cyclinD1 was detected by flow cytometry.

RESULTSThe expression of cyclinD1 in GMCs in the high glucose group increased significantly in a time-dependent manner compared with that in the control group. ISP-1 treatment significantly inhibited the up-regulated expression of cyclinD1 induced by high concentration glucose, and the expression of cyclinD1 was restored to the level of the control group 48 and 72 hrs after ISP-1 treatment.

CONCLUSIONSHigh concentration of glucose can up-regulate the expression of cyclinD1 in GMCs. ISP-1 may inhibit the up-regulated expression of cyclinD1, which might contribute to the protective effect of ISP-1 against GMC hypertrophy induced by high glucose.

Animals ; Cyclin D1 ; analysis ; Fatty Acids, Monounsaturated ; pharmacology ; G1 Phase ; Glucose ; toxicity ; Hypertrophy ; Mesangial Cells ; chemistry ; pathology ; Rats ; Rats, Sprague-Dawley

Bovine aortic endothelial cells (BAECs) were cultured with high glucose (33 mmol/L), 4 mg/L green tea polyphenols (GTPs) or 4 mg/L GTPs co-treatment with high glucose for 24 h in the presence or absence of Bafilomycin-A1 (BAF). We observed that high glucose increased the accumulation of LC3-II. Treatment with BAF did not further increase the accumulation of LC3-II. Results also showed an increased level of p62 and decreased Beclin-1. However, GTPs showed inversed trends of those proteins. Furthermore, GTPs co-treatment with high glucose decreased the level of LC3-II and a much higher accumulation of LC3-II was observed in the presence of BAF in comparison with high glucose alone. Results also showed a decreased p62 and increased Beclin-1. The results demonstrated that GTPs alleviated autophagy inhibition induced by high glucose, which may be involved in the endothelial protective effects of green tea against hyperglycemia.
Animals ; Autophagy ; drug effects ; Cattle ; Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; Gene Expression Regulation ; drug effects ; Glucose ; toxicity ; Macrolides ; pharmacology ; Polyphenols ; chemistry ; pharmacology ; Tea ; chemistry

AIMTo investigate the relation between Glu-R and the protective effect of hypothermia on oxygen and glucose deprivation (OGD) injury in hippocampal slices of rat.

METHODS(1) We had established OGD injury model in rat hippocampal slices. The changes of orthodromic population spike(OPS) during OGD and after administration of hypothermia (32 degrees C, 25 degrees C) were observed. (2) We had established Glu excitatory toxicity injury model in rat hippocampal slices. The changes of OPS after exposure to Glu and the effect of hypothermia (32 degrees C, 25 degrees C) against the Glu excitatory toxicity injury were observed. The non-NMDA receptor-mediated excitatory postsynaptic potentials (EPSP) in the CA1 area were recorded via adding the GABA-R specific agonists bicuculline (BMI) and NMDAR agonists D-(-)-2-Amino-5-phosphonopentanoic Acid (AP5) in normal artificial cerebrospinal fluid (nACSF), the NMDA receptor-mediated EPSP were recorded via adding the BMI and non-NMDA-R agonists 6,7-Dinitroquinoxaline-2, 3(1H,4H)-dione(CNQX) in nACSF. The variety of the changes of OPS during OGD14min in nACSF groups and added BMI compounded AP5 or BMI compounded CNQX ACSF groups were observed after administration of 25 degrees C hypothermia 28 min. (3) The changes of ultrastructure of CA1 area after OGD 1 h and the effect of hypothermia (25 degrees C) on it were observed.

RESULTS(1) OPS reduced and abolished quickly during OGD14min, and the recovery amplitude of OPS was very low after reoxygenation/glucose 1 h. While the time of OPS abolishing significantly elongated and the recovery of OPS was higher in hypothermia (32 degrees, 25 degrees C) groups. The effect in groups 25 degrees C was more significant than those in groups 32 degrees C. (2) In control groups, Glu (2 mmol/L, 14 min) decreased the amplitude of OPS, after the end of Glu exposure the recovery amplitude of OPS was very low. After administration of hypothermia (32 degrees C, 25 degrees C), the recovery amplitude and rate of OPS were significantly higher than those in the control groups, while the antagonism on Glu excitatory toxicity injury in H 25 degrees C was more significant than those in H 32 degrees C. The changes of OPS during OGD 14 min were no distinct difference in nACSF groups and added BMI (50 micromol/L) compounded AP5(20 micromol/L) or BMI (50 micromol/L) compounded CNQX (100 micromol/L) ACSF groups. The protection of hypothermia (25 degrees C) could not be cancelled by added AP5 compounded BMI or BMI compounded CNQX in nACSF. (3) After OGD (14 min) 1 h, the nuclear membrane of pyramidal cells in CA1 area was irregular, nucleus were homogenized, the organelle in the cytoplasm was degenerate, even more to necrosis or loss, mitochondrion swelled, ridge was vacuoles. In H 25 degrees C the nuclear membrane was regular, mitochondrion swelled only lightly. Small chromatin gathered to edge.

CONCLUSIONHypothermia shows the protective effects of against OGD injury in hippocampal slices. The mechanism is related to the antagonism of Glu excitor toxicity and maintenance the ATP level in cells, and the antagonism perhaps is mediated by NMDA-R and non-NMDA-R.

Animals ; Cell Hypoxia ; Glucose ; metabolism ; Glutamic Acid ; toxicity ; Hippocampus ; metabolism ; Hypothermia ; Membrane Potentials ; N-Methylaspartate ; metabolism ; Neurons ; metabolism ; Organ Culture Techniques ; Oxygen ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of diabetes mellitus on amplitude of distortion product otoacoustic emissions ( DPOAE) and whether streptozotocin has ototoxicity or not.

METHODSTwenty-four SD rats were divided into diabetes mellitus group, insulin therapy group and control group. Diabetes was induced by streptozotocin. The blood glucose of insulin group was controlled by insulin. The amplitude of DPOAE was tested before streptozotocin injection and 3 months, 5 months after injection, respectively.

RESULTSThe amplitude of DPOAE in diabetes rats was decreased in 3 months and there was statistical significance (P <0. 05) in 1038, 4126 and 5200 Hz, while obviously reduced in 5 months in all frequencies and there was also statistical significance (P <0. 01). The amplitude of DPOAE in all frequencies lacked of any significance between insulin therapy group and control group.

CONCLUSIONSDiabetes mellitus could induce the amplitude of DPOAE decreasing. Streptozotocin had not evident toxicity for inner ear.

Animals ; Blood Glucose ; analysis ; Diabetes Mellitus, Experimental ; physiopathology ; Ear, Inner ; drug effects ; physiopathology ; Hearing Tests ; Male ; Otoacoustic Emissions, Spontaneous ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; toxicity

OBJECTIVETo explore the effects of serum glucose and lipids by on chronically lanthanum exposure in rat.

METHODSThe Wistar rats were treated with oral exposure dose 0.1, 2 and 40 mg/kg of lanthanum chloride (LaCl(3)) respectively, after 90 days the rats were sacrificed and the blood was collected for measuring the glycosylated hemoglobin A (HbA1c), the serum was used for measuring glucose, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels.

RESULTSThere were no any differences among the control and 3 dose LaCl(3) exposed rats on the blood HbA1c and serum Glu, TG and LDL-C levels (P > 0.05). The serum TC in 0.1 and 2 mg/kg LaCl(3) dose group rats were (1.38 +/- 0.14) mmol/L and (1.37 +/- 0.26) mmol/L respectively. It was lower than that of the controls (1.57 +/- 0.14) mmol/L significantly (P < 0.05), the serum HDL-C in 0.1 mg/kg dose group rats was (0.79 +/- 0.12) mmol/L and obviously lower than that of control group rats (0.93 +/- 0.10) mmol/L (P < 0.05).

CONCLUSION0.1 - 40 mg/kg LaCl(3) chronically exposed have not greater effect on serum glucose, TG and LDL-C levels in rats, but the lower dose LaCl(3) chronic exposure might cause serum TC and HLD-C level decreasing.

Animals ; Blood Glucose ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Environmental Exposure ; Glycated Hemoglobin A ; Lanthanum ; toxicity ; Lipids ; blood ; Male ; Rats ; Rats, Wistar ; Triglycerides ; blood

OBJECTIVESTo investigate the effects of cadmium exposure on insulin expression in rats.

METHODSEighteen adult SD rats were administered cadmium subcutaneously (0.5, 1.0, and 2.0 mg/kg x bw). The effects on endocrine of pancreas were assessed. The levels of cadmium and zinc in pancreas, blood and urine glucose, serum insulin and urine NAG (N-acyetyl-beta-glucosaminidase) were determined. The gene expressions of metallothionein (MT) and insulin were also measured, and the oral glucose tolerance tests (OGTT) were carried out.

RESULTSThe contents of cadmium in pancreas in cadmium-treated rats were higher than that in the control group, which was associated with slight increase of zinc in pancreas. Cadmium-exposed rats (1.0 and 2.0 mg/kg x bw) demonstrated a marked glucose intolerance. But the levels of serum insulin did not change significantly after cadmium administration, and the UNAG had no change in Cd-treated group. The gene expression of insulin decreased in 1.0 and 2.0 mg/kg x bw cadmium-exposed groups, compared with the control group. The expression of MT-I was higher in the groups exposed to 1.0 and 2.0 mg/kg x bw cadmium while the expression of MT-II was higher in the group exposed to 2.0 mg/kg x bw cadmium.

CONCLUSIONSCadmium may be accumulated in the pancreas, resulting in the change of the expression of insulin, MT-I and MT-II genes. Cadmium can influence the biosynthesis of insulin, but does not induce the release of insulin. The dysfunction of pancreas occurs earlier than that of kidney after administration of cadmium.

Animals ; Base Sequence ; Blood Glucose ; analysis ; Cadmium ; toxicity ; DNA Primers ; Gene Expression ; drug effects ; Glucose Tolerance Test ; Glycosuria ; urine ; Insulin ; blood ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo study the effect of different treatment period, of isoniazid (INH) on the metabonomic profile of rat urine and its relationship with traditional toxicity evaluation of blood biochemical indicators and histopathology and to explore the feasibility of metabonomics in the application of drug toxicity.

METHODSSixty male Wistar rats were orally administrated with 0, 50, 100, 200, and 400 mg x kg(-1) INH for 3, 7, and 14 days, respectively. Rat urine was then collected and its 1H nuclear magnetic resonance (NMR) spectra were acquired. All animals underwent traditional toxicity evaluation.

RESULTSHepatotoxicity was revealed by traditional toxicity evaluation in rats treated with higher dosage and longer treatment of INH. Time-response relationship existed during the treatment. Time-dependent metabonomics changes conformed with the results of traditional toxicity evaluation. The urine metabonomics showed a trajectory bias from those of the controls or pre-administration, and such bias exaggerated along with the prolongation of treatment, indicating a severer toxic injury. Along with the increase of the concentrations of urinary taurine and glucose and the decrease of the concentrations of urinary citrate and 2-oxoglutarate, the 1H NMR spectra of urine in rats treated with INH also changed.

CONCLUSIONSThe metabonomics technique can distinguish the onset and development of toxicity, which helps track and identify biomarkers. The hepatic toxicity induced by INH is related to the injury of mitochondrial function, reduction of energy metabolism in tricarboxylic acid cycle, and perturbations in the metabolism of glucose and lipid. The effect of INH on the rat urine metabonomic profile is related with INH toxicology. Therefore, metabonomics can be recognized as an ideal technique to explore and evaluate the drug toxicities.

Animals ; Antitubercular Agents ; toxicity ; Biomarkers ; chemistry ; urine ; Chemical and Drug Induced Liver Injury ; metabolism ; urine ; Citric Acid ; chemistry ; urine ; Citric Acid Cycle ; drug effects ; Glucose ; chemistry ; metabolism ; Isoniazid ; toxicity ; Ketoglutaric Acids ; chemistry ; urine ; Lipids ; Magnetic Resonance Spectroscopy ; Male ; Metabolome ; drug effects ; Mitochondria ; drug effects ; Rats ; Rats, Wistar ; Taurine ; chemistry ; urine ; Toxicity Tests ; methods

BACKGROUND: A1chieve(R) was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. METHODS: Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. RESULTS: Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7+/-15.9 to 72.5+/-13.5) while the mean body weight was slightly increased (0.6+/-3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%+/-2.2%, 2.5+/-4.7 mmol/L, and 4.0+/-6.4 mmol/L, respectively. CONCLUSION: The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.
Biphasic Insulins ; Body Weight ; Diabetes Mellitus, Type 2 ; Drug Toxicity ; Fasting ; Glucose ; Hemoglobins ; Humans ; Incidence ; Insulin ; Insulin Aspart ; Insulin, Isophane ; Insulin, Long-Acting ; Patient Selection ; Plasma ; Quality of Life ; Republic of Korea ; Treatment Outcome ; Insulin Detemir