• Toxicological Research
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• 제24권4호
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• pp.281-287
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• 2008

Impairment of hepatic metabolism of sulfur-containing amino acids has been known to be linked with induction of liver injury. We determined the early changes in the transsulfuration reactions in liver of rats challenged with a toxic dose of $CCl_4$ (2 mmol/kg, ip). Both hepatic methionine concentration and methionine adenosyltransferase activity were increased, but S-adenosylmethionine level did not change. Hepatic cysteine was increased significantly from 4 h after $CCl_4$ treatment. Glutathione (GSH) concentration in liver was elevated in $4{\sim}8$ h and then returned to normal in accordance with the changes in glutamate cysteine ligase activity. Cysteine dioxygenase activity and hypotaurine concentration were also elevated from 4 h after the treatment. However, plasma GSH concentration was increased progressively, reaching a level at least several fold greater than normal in 24 h. ${\gamma}$-Glutamyltransferase activity in kidney or liver was not altered by $CCl_4$, suggesting that the increase in plasma GSH could not be attributed to a failure of GSH cycling. The results indicate that acute liver injury induced by $CCl_4$ is accompanied with extensive alterations in the metabolomics of sulfurcontaining amino acids and related substances. The major metabolites and products of the transsulfuration pathway, including methionine, cysteine, hypotaurine, and GSH, are all increased in liver and plasma. The physiological significance of the change in the metabolomics of sulfur-containing substances and its role in the induction of liver injury need to be explored in future studies.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.137-137
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• 1998

Stability, efficacy, absorption and toxicity of a new nasal spray formulation including salmon calcitonin were studied in the laboratory animals. After the effects of many excipients on the stability of salmon calcitonin were evaluated using HPLC system, we selected taurine. Our experimental composition of salmon calcitonin contains taurine as a stabilizer and HPMC (hydroxypropylmethyl cellulose) as an adhesive polymer. After intranasal administration of salmon calcitonin formulations, Mia$\^$(R)/, Men$\^$(R)/ and experimental composition, 22 IU to rats, the reduction percentages of calcium concentration in plasma (ΔD%) were 16.3%, 12.9% and 20.8%, respectively. After intranasal administration of Mia$\^$(R)/, Men$\^$(R)/ and experimental composition to rats, C$\sub$MAX/ (205${\pm}$161, 244${\pm}$117, and 330${\pm}$202 pg/$m\ell$, respectively) and AUC (41585${\pm}$22070, 41191${\pm}$19125, and 63357${\pm}$43126 pg. min/$m\ell$, respectively) were calculated. The permeation coefficients 10$\^$-7/,cm/sec) of salmon calcitonin in Mia$\^$(R)/, Men$\^$(R)/ and experimental composition using Ussing chamber with rabbit nasal mucosa were 4.7${\pm}$1.5, 0.75${\pm}$0.4 and 5.3${\pm}$1.1, respectively. The experimental composition with taurine and HPMC was proved to be excellent because it improved the stability of salmon calcitonin and inhanced the absorption of salmon calcitonin and was not irritative to the nasal mucosa.

• Asian-Australasian Journal of Animal Sciences
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• 제30권11호
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• pp.1633-1642
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• 2017

Objective: Evaluation of exercise effects in racehorses is important in horseracing industry and animal health care. In this study, we compared metabolic patterns between before and after exercise to screen metabolic biomarkers for exercise effects in thoroughbreds. Methods: The concentration of metabolites in muscle, plasma, and urine was measured by $^1H$ nuclear magnetic resonance (NMR) spectroscopy analysis and the relative metabolite levels in the three samples were compared between before and after exercise. Subsequently, multivariate data analysis based on the metabolic profiles was performed using orthogonal partial least square discriminant analysis (OPLS-DA) and variable important plots and t-test was used for basic statistical analysis. Results: From $^1H$ NMR spectroscopy analysis, 35, 25, and 34 metabolites were detected in the muscle, plasma, and urine. Aspartate, betaine, choline, cysteine, ethanol, and threonine were increased over 2-fold in the muscle; propionate and trimethylamine were increased over 2-fold in the plasma; and alanine, glycerol, inosine, lactate, and pyruvate were increased over 2-fold whereas acetoacetate, arginine, citrulline, creatine, glutamine, glutarate, hippurate, lysine, methionine, phenylacetylglycine, taurine, trigonelline, trimethylamine, and trimethylamine N-oxide were decreased below 0.5-fold in the urine. The OPLS-DA showed clear separation of the metabolic patterns before and after exercise in the muscle, plasma, and urine. Statistical analysis showed that after exercise, acetoacetate, arginine, glutamine, hippurate, phenylacetylglycine trimethylamine, trimethylamine N-oxide, and trigonelline were significantly decreased and alanine, glycerol, inosine, lactate, and pyruvate were significantly increased in the urine (p<0.05). Conclusion: In conclusion, we analyzed integrated metabolic patterns in the muscle, plasma, and urine before and after exercise in racehorses. We found changed patterns of metabolites in the muscle, plasma, and urine of racehorses before and after exercise.