• Journal of Food Hygiene and Safety
• /
• v.18 no.3
• /
• pp.153-160
• /
• 2003

This study was performed to determine the urinary metabolites of methidathion in rats. Urine samples were collected for 24 hours in metabolic cages following after oral administration and dermal application of methidation to rats. The urinary metabolites were identified by GC/MS and the excretion time courses of urinary dialkyl phosphate metabolites were analyzed by CG/FPD. The results obtained are summarized as follows: Three dialkyl phosphate metabolites, DMP, DMTP. and DMDTP, were detected in the rat urine. Urinary dialkyl phosphate metabolites were identified on the basis of their mass spectra by GC/MS. The molecular ions of DMP, DMTP,and DMDTP, were identified at m/z 198, and m/z 158, respectively. A comparison of excretion time courses of urinary dialkyl phosphate metabolites between the orally administrated and dermally applicated rats were also established, After oral administration, 79.2% of DMP, 93.9% of DMTP, and 83.0% of DMDTP were excreted into the urine by 12, 24, and 12 hours, respectively. After dermal application, 71.1% of DMP, 82.8% of DMTP 87.7% of DMDTP were excreted into the urine by 24, 48, 48 hours, respectively. Consequently, almost all of the dialkyl phosphates in oral administration were excreted within 48 hours. However, the metabolites in dermal application were excreted up to 168 hours. In the study, three urinary metabolites of methidation, DMP, DMTP and DMDTP, were detected in the rat both after oral administraion and dermal application with methidathion. And the urinary excretion in dermal application was more delayed than that in oral administration. Based on the results, it tis suggested that three urinary dealkyl phosphates, DMP, DMTP, and DMDTP, could be used as the biomarkers of exposure for methidathion.

• Biomolecules & Therapeutics
• /
• v.1 no.2
• /
• pp.211-219
• /
• 1993

The general and some pharmacological actions of DWP 302 were investigated in animals and the following results were obtained. In central nervous system, DWP 302 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in the mice and body temperature in the rat. DWP 302 showed no depressive action on the convulsion induced by strychnine and electronic shock. From these results, DWP 302 was considered to have no or little pharmacological effect on the central nervous system. Furthermore, DWP 302 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 302 showed neither contractive nor relaxing effects against the acetylcholine ($10^{-6}g/mι$), histamine ($10^{-6}g/mι$) and $BaCl_2$ ($10^{-4}g/mι$) at a concentration of $1.9{\times}10^{-4}g/mι$ in bath. But it caused a slight increase in basal tone at a concentration of $6.3{\times}10^{-4}g/mι$ and this effect was inhibited by atropine $10^{-7}g/mι.$ In the isolated trachea and vas deference, DWP 302 showed no effect on the contractions produced by histamine and norepinephrine, respectively. And DWP 302 showed no effect on the contractions produced by acetylcholine and oxytocin in the isolated nonpregnant rat uterus. DWP 302 had no effect on bile excretion, urine volume, pH and gastrointestinal motility, But, DWP 302 showed a significant inhibitory effect on gastric secretion in the rat.

• The Journal of Internal Korean Medicine
• /
• v.29 no.3
• /
• pp.787-799
• /
• 2008

Objective : Diabetic nephropathy is the most common cause of end stage renal disease. AGE, $TGF-{\beta}1$ type IV collagen, and macrophage/monocyte infiltration are the main factors of diabetic nephropathy. We investigated the effects of Salvia miltiorrhiza on renal function and histopathological changes in streptozotocin(STZ)-induced diabetic nephropathy rat model. Methods : Diabetes was induced in male Sprague-Dawley rats(290${\pm}$10g) by injecting STZ(45mg/kg) into the tail vein. Rats were divided into 3 groups(n = 6): normal, control, and salvia. After 8 weeks of administration of Salvia miltiorrhiza extract on the Salvia group, we checked 24 hrs urine, blood biochemistry and renal tissue to evaluate renal function and histopathological changes by examining parameters including albuminuria, BUN, creatinine, cholesterol, LDL, TG, macrophage/monocyte antigen(ED-1), $TGF-{\beta}1$, AGE, and type IV collagen. Results : Salvia miltiorrhiza decreased the amount of 24hrs proteinuria, and inhibited histopathological changes of diabetic nephropathy including the expression and accumulation of various factors which could promote development of diabetic nephropathy. Conclusion : These findings suggest that Salvia miltiorrhiza might protect the renal function and inhibit the development of renal injury by regulating factors including AGE, $TGF-{\beta}1$ Type IV collagen, macrophage and monocyte infiltration. So Salvia miltiorrhiza can be used for diabetic patients to prevent the progression of diabetic nephropathy.

• Biomolecules & Therapeutics
• /
• v.4 no.1
• /
• pp.78-83
• /
• 1996

The pharmacokinetics and tissue distribution of DA-3285 (recombinant human erythropoietin, recently manufactured by Research Laboratories of Dong-A Pharmaceutical Company) were studied in the laboratory animals. The plasma, urine, and tissue concentration of DA-3285 were measured by a double-antibody sandwich enzyme immunoassay. After intravenous administration of DA-3285, 20, 100, 500 and 2500 units/kg to rats, the plasma concentrations declined polyexponentially with the terminal half-lives of 2.15, 2.10, 2.31, and 2.35 hr, respectively. Total body clearance (20.7∼26.6 mι/hr/kg) and apparent volume of distribution at steady state (57.2∼70.1 mι/kg) were independent of the dose and AUC increased proportionally with the dose. The renal clearance was much lower than total body clearance, suggesting that extrarenal clearance, presumably metabolism , plays a significant role in elimination of DA-3285. In all rat tissues, the tissue to plasma ratios were smaller than unity, indicating less affinity of DA-3285 to rat tissues and was proved by considerably less value of Vdss. After 3 times a week for consecutive 3 weeks i.v. administration of DA-3285, 100 units/kg to rats, the plasma concentrations and pharmacokinetic parameters of DA-3285 were not significantly different from those in a single administration. After s.c. administration to the rat, plasma concentrations of DA-3285 peaked at 6 hr and the extent of bioavailability was 26.7%. In mice, rabbits and dogs, at DA-3285 dose of 100 units/kg, the mean terminal haw-lives were 2.78, 3.05, and 4.01 hr, respectively. Compared with reported data in the literatures, DA-3285 has similar properties to rh-EPO manufactured by other companies in view of pharmacokinetics.

• Toxicological Research
• /
• v.20 no.3
• /
• pp.195-203
• /
• 2004

4-Tert-Octylphenol (OP) is a surfactant additive widely used in the manufacture of a variety of detergents and plastic products. OP can disrupt endocrine function in humans and animals. This study was carried out to obtain toxicokinetic parameters of OP in male Sprague-Dawley (SD) rats. Male rats were administered with OP by single oral application of 200 mg/kg body weight. Blood, urine and tissues samples were taken at several time intervals after administration. Analysis of samples for OP was performed by column-switching high performance liquid chromatography (HPLC). In addition, we exam-ined tissue distribution and accumulation of OP after single oral application of 50, 100, and 200 mg/kg, single intravenous injection of 1, 5 and 10 mg/kg or daily application of 50 mg/kg for 14 consecutive days. After single oral administration of 200 mg/kg, Cmax of 213 $\pm$ 123 ng/ml was reached within the first 1.3 hr (Tmax) in the plasma. AUC was calculated for 1,333$\pm$484 ngㆍhr/ml. The final elimination half-life of plasma was longer than that of urine, but urinary clearance was lower than oral. A very small fraction of OP (Fe < 0.0017%) was excreted in urine within 24 hr. These results indicated that the major excretion route of OP was not urine. The mean maximal tissue distribution of OP was obserbed at 6 hr after treatment and slowly decreased time-dependently. High OP concentrations were detected in fat at 24 hr. The OP in fat was slowly released with longer elimination half-life and lower clearance than that of other tissues. OP was not accumulated in the liver following single oral application but 14-day oral treatments resulted in two-fold accumulation. It was probably due to the saturation of detoxification pathways. On the other hand, the mRNA expression of cytochrome P450 isoforms except CYP2C11 was not affected by OP at any dose. The expression of CYP2C11 mRNA decreased in a dose-dependent manner. This result suggests that OP changes expression of the male-specific cytochrome P450 isoforms in rat liver, and these changes are closely related to the toxic and estrogenic effect of OP.

• Korean Journal of Environmental Biology
• /
• v.22 no.4
• /
• pp.513-518
• /
• 2004

Pine needle oil and Korean medicinal herbs (KMH) are known as effective therapeutic agents on various blood vessel disease. We have already reported the ameliorative effect of complex of pine needle oil and Korean medicinal herbs against hyperlipidemia. But safety and non - toxicity of pine needle oil and Korean medicinal herbs to normal animal cells have not been studied clearly. In this study, we investigated whether pine needle oil and Korean medicinal herbs show side effects on rat or not. These materials were administered to rats, and subacute toxicity was examined by measuring the hematological values, CBC differentiation, biochemical levels of blood (TP, total protein; albumin; ALP, alkaline phosphotase; AST, aspatate aminotrans- ferase; ALT, alanine aminotransferase; T-Chol., total cholesterol; T-Bil., total bilirubin) and urine analysis, suggesting that the sample have no side effects and cytotoxicity. These results indicate that the complex of pine needle oil and Korean medicinal herbs may effective non- toxic, safety therapeutic agents on hepatocytes and hyperlipidemia.

• Environmental Mutagens and Carcinogens
• /
• v.22 no.4
• /
• pp.279-288
• /
• 2002

According to the epidemiological studies in chromium workers, hexavalent chromium is associated with the risk of lung cancer. Cellular oxidative damages by reactive oxygen species produced by hexavalent chromium exposure may play an important role in the carcinogenesis process. We investigated the availabilities of malondialdehyde measurement for the assessments of oxidative damages from chromium exposure with an experimental inhalation study in vivo. Lipid peroxidation, one kind of cellular oxidative damage, was measured in blood plasma of the rats which inhaled the hexavalent chromium mist for 1, 2 and 3 weeks. The concentrations of malondialdehyde (MDA), the metabolite of lipid peroxidation, in all exposed groups were higher than those of controls with dose-dependant manner. The levels of MDA were also correlated with urine chromium levels of the rats. Therefore, MDA as an indicator of lipid peroxidation could be proper biologic marker for the assessment of the oxidative damage from chromium exposure, which might be involved in carcinogenesis.

• Toxicological Research
• /
• v.22 no.2
• /
• pp.135-144
• /
• 2006

This study was performed to evaluate repeated-dose toxicities of STB-HO-BM in Sprague-Dawley rats. STB-HO-BM was administered orally to rats at dose levels of 0, 100, 300 and 1,000 mg/kg/day for 13 weeks. In recent study, there were no dose related changes in mortality, clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with STB-HO-BM. Gross and histopathological findings revealed no evidence of specific toxicity related to STB-HO-BM. These results suggest that the oral no observed adverse effect level (NOAEL) of STB-HO-BM may be over 1,000 mg/kg in rats.

• Nutritional Sciences
• /
• v.6 no.2
• /
• pp.94-99
• /
• 2003

The purpose of this study was to investigate in vivo lipid peroxidation in rats under conditions of streptozotocin-induced oxidative stress and the antioxidant effects of probucol. In vivo lipid peroxidation was observed by measuring low molecular weight aldehydes and related carbonyl compounds in rat urine. Three groups of male Wistar rats weighing 165-190 g were used: normal (N), streptozotocin-induced oxidative stress (OS) and oxidative stress plus probucol treatment (P). following streptozotocin treatment of the rats, a variety of secondary lipid peroxidation products were increased. The levels of butanal, hexanal, hex-2-enal, kept-2-enal, octanal, non-2-enal, deca-2,4-dienal, 4-hydroxyhex-2-enal, 4-hydroxyno n-2-enal, malondi aldehyde(MDA), and unknown carbonyl compounds were significantly increased in the oxidative stress group compared to the control group. Treatment with probucol resulted in significant decreases in buoal, hexanal, hex-2-enal, octanal, deca-2,4-dienal, 4-hydroxyhex-2-enal, MDA and unknown carbonyl compounds. Hept-2-enal, hepta-2,4-dienal and non-2-enal appeared to have a tendency to decrease due to pobucol treatment.

• Journal of Society of Preventive Korean Medicine
• /
• v.7 no.1
• /
• pp.55-66
• /
• 2003

Osteoporosis is characterized by bone loss and mobidity with osteoporotic fracture. This study was performed to evaluate the effect of on the bone mass and its related factors in estrogen-deficient animal model. The model rats of osteoporsis showed a significant decrease in bone density, bone ash density, calcium content of femur bone. At the 14th day after ovariectomy-surgery, rats were administered with DBE, extract of Dioscorea batatas, per orally, and continued for 10 weeks. And osteoporosis related parameters were determined to investigate the effect of DBE. Osteoporetic rats showed lower serum estrogen level, higher body weight than normal rats, and showed atrophy of uterine horns. DBE showed inhibitory effect on bone loss in osteoporetic condition, and reduced the increase of ALP activity and osteocalcin level in serum, and reduced the increase of OH-proline level in urine. But, DBE had no effect on cell proliferation and ALP activity in rat calvarial cell culture.