• Mass Spectrometry Letters
• /
• v.10 no.3
• /
• pp.88-92
• /
• 2019

A sensitive analytical method of rhodanthpyrone A in rat plasma was developed using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Rhodanthpyrone A and rhodanthpyrone B (internal standard) in rat plasma were extracted by a liquid-liquid extraction method with ethyl acetate. This extraction method gave results in high and reproducible extraction recovery in the range of 73.75-79.90% with no interfering peaks around the peak elution time of rhodanthpyrone A and B. The standard calibration curves for rhodanthpyrone A ranged from 0.5 to 2000 ng/mL were linear with $r^2$ > 0.994 and the inter- and intra-day accuracy and precision and the stability were within acceptance criteria. Using this validated analytical method, pharmacokinetics of rhodanthpyrone A following intravenous and oral administration of rhodanthpyrone A at doses of 2 mg/kg and 30 mg/kg, respectively, were investigated. Rhodanthpyrone A in rat plasma showed multi-exponential elimination pattern with high clearance and volume of distribution values. The absolute oral bioavailability of this compound was calculated as 3.7%. Collectively, the newly developed sensitive LC-MS/MS analytical method of rhodanthpyrone A could be successfully applied to investigate the pharmacokinetic properties of this compound and would be useful for the further studies on the efficacy, toxicity, and biopharmaceutics of rhodanthpyrone A.

• Proceedings of the SCSK Conference
• /
• 1999.10a
• /
• pp.145-154
• /
• 1999

A novel retinol derivative, polyethoxylated retinamide (Medimin A) was synthesized, as an anti-aging agent. Collagen synthesis, skin permeation, stability, and toxicity of Medimin A were evaluated and compared with those of retinol and retinyl palmitate. In vitro collagen synthesis was evaluated by quantitative assay of [$^3H$]-proline incorporation into collagenase sensitive protein in fibroblast cultures. For in vitro skin permeation experiments, Franz diffusion cells (effective diffusion area: $1, 766{\;}\textrm{cm}^2$) and the excised skin of female hairless mouse aged 8 weeks were used The stabilities of retlnoids were evaluated at two different temperature ($25{\;}^{\circ}C$ and $40{\;}^{\circ}C$) and under UV in solubilized state and in OW emulsion. To estimate the safety, acute oral toxicity, acute dermal toxicity, primary skin irritation, acute eye irritation and human patch test were performed The effect of Medimin A on collagen synthesis was similar to that of retinol. The skin permeability of Medimin A was higher than those of retinol and retinyl palmitate. The Medimin A was more stable than retinol and retinyl palmitate. Medimin A was nontoxic in various toxicological tests. These results suggest that Medimin A would be a good anti-aging agent for enhancing bioavailability and stability.

• Journal of Pharmaceutical Investigation
• /
• v.41 no.4
• /
• pp.239-247
• /
• 2011

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.

• Journal of Soil and Groundwater Environment
• /
• v.16 no.4
• /
• pp.23-30
• /
• 2011

Risk based pollution level of Pb and Cd in metal contaminated soils depending on physicochemical properties of soil in a target site was assessed using biotic ligand model. Heavy metal activity in soil solution defined as exposure activity (EA) was assumed to be toxic to Vibrio fischeri and soil organisms. Predicted effective activity (PEA) determined by biotic ligand model was compared to EA value to calculate risk quotient. Field contaminated soils (n = 10) were collected from a formes area and their risk based pollution levels were assessed in the present study using the calculated risk quotient. Concentrations of Pb determined by aqua regia were 295, 258, and 268 mg/kg in B, H and J points and concentrations of Cd were 4.73 and 6.36 mg/kg in G and I points, respectively. These points exceeded the current soil conservation standards. However, risk based pollution levels of the ten points were not able to be calculated because concentrations of Pb and Cd in soil solution were smaller than detection limits or one (i.e., non toxic). It was because heavy metal activity in soil solution was dominant toxicological form to organisms, not a total heavy metal concentration in soil. In addition, heavy metal toxicity was decreased by competition effect of major cations and formation of complex with dissolved organic carbon in soil solution. Therefore, it is essential to consider site-specific factors affecting bioavailability and toxicity for estimating reliable risk of Pb and Cd.

• Toxicological Research
• /
• v.25 no.2
• /
• pp.79-84
• /
• 2009

Cerium oxide nanoparticles (size: 30 nm) were prepared by the supercritical synthesis method, Acute oral toxicity and tissue distribution of the nanoparticles were evaluated by a single administration in rats. Oral administration of the nanoparticles to the rats did not lead to death when the animals were treated by a dose of 5 g/kg (high dose) as well as 100 mg/kg (low dose). Abnormal clinical signs, changes in serum biochemistry and hematology were not observed in high-dose treated group compared to the vehicle control group. Lesions in liver, lung and kidney were not observed in high-dose treated group by histopathological examination. Tissue distribution analysis in liver, kidney, spleen, lung, testis and brain was performed on day 1, day 7 and day 14 after treatment. The average values of the accumulated cerium oxide nanoparticles were elevated in all tissues but statistical significance was only shown in lung. Low levels of tissue distributions after a single oral administration seem to be the low bioavailability of the nanoparticles.

• Korean Journal of Environmental Agriculture
• /
• v.37 no.2
• /
• pp.146-149
• /
• 2018

BACKGROUND: Selenium is an essential element for all life forms but can be toxic above certain narrow levels. Prevalent forms of selenium in oxic environment are selenium oxyanions such as selenite and selenate, which may be contaminants in soils and water bodies. Bacterial reduction of more mobile selenium species (selenite or selenate) to less mobile elemental selenium may suggest a benign solution for alleviating toxicity and bioavailability of the selenium species. METHODS AND RESULTS: A facultative anaerobic bacterium, Citrobacter strain SE4-1 was isolated from the contaminated stream sediments and found to effectively reduce selenite to elemental selenium. Aqueous phase of selenite was analyzed by inductively couple plasma spectroscopy and the precipitated sphere-shaped elemental selenium was observed by transmission electron microscopy. CONCLUSION: The bacterial strain SE4-1 isolated in this study suggests a potential role in biogeochemical cycle of selenium by the selenite reduction in the stream environment, and potentials for biotechnological applications to reduceselenium concentrations in selenium-contaminated systems such as wastewater, soil, and groundwater.

• Journal of Korean Society on Water Environment
• /
• v.29 no.5
• /
• pp.691-702
• /
• 2013

This review paper summarizes the theory, application, and potential drawbacks of diffusive gradient in thin film (DGT) probe which is a widely used in-situ passive sampling technique for monitoring inorganic contaminants in aquatic environments. The DGT probe employs a series of layers including a filter membrane, a diffusive hydrogel, and an ionic exchange resin gel in a plastic unit. The filter side is exposed to an aquatic environment after which dissolved inorganic contaminants, such as heavy metals and nuclides, diffuse through the hydrogel and are accumulated in the resin gel. After retrieval, the contaminants in the resin gel are extracted by strong acid or base and the concentrations are determined by analytical instruments. Then aqueous concentrations of the inorganic contaminants can be estimated from a mathematical equation. The DGT has also been used to monitor nutrients, such as ${PO_4}^{3-}$, in lakes, streams, and estuaries, which might be helpful in assessing eutrophic potential in aquatic environments. DGT is a robust in-situ passive sampling techniques for investigating bioavailability, toxicity, and speciation of inorganic contaminants in aquatic environments, and can be an effective monitoring tool for risk assessment.

• Korean Journal of Ecology and Environment
• /
• v.41 no.1
• /
• pp.66-72
• /
• 2008

Total metals, soluble metals, and bioavailable metals were monitored at the sediments of urban lakes located in Seoul, Korea during spring season 2006. The metals measured were zinc, arsenic, chromium, copper, nickel, and cadmium, which are known to be toxic to human health and ecosystems. The main sources of heavy metals in the lakes were urban runoff and atmospheric deposition associated with air pollution in urban areas. Extraction by using a weak electrolyte solution (0.1 M $Ca(NO_3)_2$) was used to predict bioavailability of the metals. Among the six heavy metals studied, copper was the most bioavailable, based the weak electrolyte extraction techniques. Since metal toxicity is related to metal bioavailability, the results were consistent with the high ecotoxicity of copper, compared to other heavy metals. Overall results suggest that there was no direct relationship between total and bioavailable metal concentration, although zinc, copper and cadmium show some relationships.

• The Korean Journal of Food And Nutrition
• /
• v.21 no.4
• /
• pp.397-402
• /
• 2008

Over the past few years, anthocyanin has been demonstrated to exert potentially anti-oxidative and bioavailability effects including anti-cardiovascular disease and cancer-preventive effects in humans. This study was conducted to assess the toxicity of anthocyanin extracts from black soybean seed coats via oral administration in a mice feeding test. The final anthocyanin-containing products induced signs of toxicity on mortality in the 4-week feeding test. The incidence of clinical signs and changes in body and organ weight were also not observed in all anthocyanin-treated groups as compared with the control groups. In hematology analysis, RBC indices concluding MCV, MCH, and MCHC and WBC differential counting such a NEU, LYM, MONO, EOS, and BASO evidenced no significant differences between the anthocyanin treatment and control groups. The biochemical parameters in serum analysis - ALT, AST, BUN, Crea etc.- were also not significantly altered in those groups. Absolute and relative organ weights were not increased after 4 weeks of treatment with anthocyanin extracts in mice. In conclusion, anthocyanin extracts from the black soybean has biological activity without any toxic effects, which also suggests that the consumption of soy containing anthocyanin products may be a good source for health and medical supplies.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.25 no.4 s.34
• /
• pp.145-154
• /
• 1999

A novel retinol derivative, polyethoxylated retinamide(Medimin A) was synthesized, as an anti-aging agent. Collagen synthesis, skin permeation, stability, and toxicity of Medimin A were evaluated and compared with those of retinol and retinyl palmitate. In vitro collagen synthesis was evaluated by quantitative assay of $[^3H]-proline$ incorporation into collagenase sensitive protein in fibroblast cultures. For in vitro skin permeation experiments, Franz diffusion cells(effective diffusion area: 1,766 $cm^2$) and the excised skin of female hairless mouse aged 8 weeks were used, The stabilities of retinoids were evaluated at two different temperature($25^{\circ}C\;and\;40^{\circ}C$) and under UV in solubilized state and in O/W emulsion. To estimate the safety, acute oral toxicity, acute dermal toxicity, primary skin irritation, acute eye irritation and human patch test were performed. The effect of Medimin A on collagen synthesis was similar to that of retinol. The skin permeability of Medimin A was higher than those of retinol and retinyl palmitate. The Medimin A was more stable than retinol and retinyl palmitate. Medimin A was nontoxic in various toxicological tests. These results suggest that Medimin A would be a good anti-aging agent for enhancing bioavailability and stability.