• Title/Summary/Keyword: Serum Metabolism

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Effects of Organic Ca Supplements on Ca Bioavailability and Physiological Functions in Ovariectomized Osteoporotic Model Rats (난소절제 골다공증 흰쥐모델에서 유기태 칼슘보충제가 칼슘 이용성과 생리기능에 미치는 영향)

  • Cho, Su-Jung;Park, Mi-Na;Kim, Hee-Kyong;Kim, Jae-Hong;Kim, Min-Ho;Kim, Wan-Sik;Lee, Yeon-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.5
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    • pp.665-672
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    • 2011
  • We evaluated the effects of organic Ca supplements chelated with milk protein (CaMP) in ovariectomized osteoporotic rats. Eight week-old Sprague-Dawley female rats were ovariectomized and fed a low $CaCO_3$ diet (0.1%) for 4 weeks to create an osteoporotic model. At that point, L4-$CaCO_3$ rats were sacrificed and the rest of the rats were divided into 4 groups, each of which was fed an experimental diet for 4 weeks: low-$CaCO_3$ (0.1%; L8-$CaCO_3$) and CaMP at 3 Ca levels: low (0.1%; L8-CaMP), normal (0.5%; N8-CaMP), and high (1.5%; H8-CaMP). Daily weight gain, serum ALP, weight and breaking force of femurs, Ca content of the lumbar, and Ca absorption were measured. Daily weight gain increased in the N8-CaMP and H8-CaMP groups compared to the low Ca groups. The ALP activity in the CaMP-fed rats was significantly lower than in the $CaCO_3$-fed rats. Both breaking force and femur weight were higher in the N8-CaMP and H8-CaMP groups compared to the L8-$CaCO_3$ group. Ca content of the lumbar increased dose-dependently with Ca intake levels of CaMP. Ca absorption rates of the CaMP-fed rats increased more than that of the rats fed low Ca levels of $CaCO_3$. These results demonstrate that the CaMP supplement had positive effects on bone metabolism and Ca bioavailability in ovariectomized osteoporotic rats. Therefore, CaMP may be recommended as a useful Ca supplement to prevent bone loss in osteoporosis.

Effects of Processed Cuttlefish on Lipid and Immunoglobulin Levels in Mice Blood (가공오징어의 섭취가 쥐의 혈중 지질 조성 및 항체 형성 농도에 미치는 영향)

  • Jeong, Hyang-Suk;Ha, Ji-Hye;Oh, Sung-Ho;Kim, Seoung-Seop;Jeong, Myoung-Hoon;Choi, Geun-Pyo;Park, Uk-Yeon;Park, Sung-Jin;Lee, Hyeon-Yong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.3
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    • pp.474-479
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    • 2010
  • The content levels of taurine, DHA, and EPA of dried cuttlefish powder were $11.67{\pm}6.62\;g/kg$, $3001.11{\pm}11.42\;mg/100\;g$ and $688.13{\pm}10.51\;mg/100\;g$, respectively, which were 10~20% higher than those of the salt processed cuttlefish. After feeding dried and salt processed cuttlefish for 4 weeks, total cholesterol concentrations in mice blood were 81.3 mg/dL and 88.1 mg/dL, respectively, which was higher than 78.9 mg/dL of the control. It was also found that dried cuttlefish increased HDL-cholesterol concentrations to 71.6 mg/dL, compared to 63.1 mg/dL of salt processed cuttlefish. The triglyceride contents of dried sample was higher than that of processed sample. Blood glucose concentrations in mice fed dried or salt processed cuttlefish were 77.7 mg/dL and 90.3 mg/dL, respectively. IgG levels increased to 48.1 ng/mL by feeding the processed cuttlefish, compared to 40.3 ng/mL of the dried cuttlefish. Therefore, by analysis of serum lipid, it can be suggested that processed cuttlefish can improve immune activities through adding taurine and polyunsaturated fatty acids.

Effect of Fermented Cucumber Beverage on Ethanol Metabolism and Antioxidant Activity in Ethanol-treated Rats (오이 발효음료가 만성적으로 에탄올을 급여한 흰쥐의 에탄올 대사와 항산화방어계에 미치는 영향)

  • Lee, Hae-In;Seo, Kwon-Il;Lee, Jin;Lee, Jeom-Sook;Hong, Sung-Min;Lee, Ju-Hye;Kim, Myung-Joo;Lee, Mi-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.8
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    • pp.1099-1106
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    • 2011
  • Cucumber fermentation has been used as a means of preservation. This study was performed to investigate the effects of fermented cucumber beverage (CF) containing beneficial materials for an ethanol hangover based on Hovenia dulcis (SKM) on ethanol-induced hepatotoxicity. Male Sprague-Dawley rats were randomly divided into three groups: ethanol control, ethanol plus SKM, and ethanol plus CF+SKM. SKM or CF+SKM was orally administered at a dose of 7 mL/kg body weight once per day for 5 weeks. Control rats were given an equal amount of water. CF+SKM significantly lowered plasma ethanol levels, whereas SKM tended to decrease the levels compared to the control. Both SKM and CF+SKM significantly lowered the plasma acetaldehyde levels and serum transaminase activities compared to those in the control. SKM and CF+SKM did not affect hepatic alcohol dehydrogenase activity; however, it significantly inhibited cytochrome P450 2E1 (CYP2E1) activity. Hepatic aldehyde dehydrogenase (ALDH) activity was significantly higher in the SKM and CF+SKM groups than that in the control group. Plasma acetaldehyde concentration was significantly correlated with hepatic CYP2E1 (r=0.566, p<0.01) activity and ALDH (r=-0.564, p<0.01) activity. Hepatic superoxide dismutase and catalase activities as well as glutathione content increased with the SKM and CF+SKM administration, whereas lipid peroxide content decreased significantly. Furthermore, SKM and CF+SKM lowered plasma and hepatic lipid content and lipid droplets compared to those in the control group. These results indicate that SKM and CF+SKM exhibit hepatoprotective properties partly by inhibiting CYP2E1 activity, enhancing ALDH activity and stimulating the antioxidant defense systems in ethanol-treated rats.

Validation of Stem-loop RT-qPCR Method on the Pharmacokinetic Analysis of siRNA Therapeutics (Stem-loop RT-qPCR 분석법을 이용한 siRNA 치료제의 생체시료 분석법 검증 및 약물 동태학적 분석)

  • Kim, Hye Jeong;Kim, Taek Min;Kim, Hong Joong;Jung, Hun Soon;Lee, Seung Ho
    • Journal of Life Science
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    • v.29 no.6
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    • pp.653-661
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    • 2019
  • The first small interfering RNA (siRNA) therapeutics have recently been approved by the Food and Drug Administration in the U.S., and the demand for a new RNA therapeutics bioanalysis method-which is essential for pharmacokinetics, including the absorption, distribution, metabolism, and excretion of siRNA therapeutics-is rapidly increasing. The stem-loop real-time qPCR (RT-qPCR) assay is a useful molecular technique for the identification and quantification of small RNA (e.g., micro RNA and siRNA) and can be applied for the bioanalysis of siRNA therapeutics. When the anti-HPV E6/E7 siRNA therapeutic was used in preclinical trials, the established stem-loop RT-qPCR assay was validated. The limit of detection was sensitive up to 10 fM and the lower limit of quantification up to 100 fM. In fact, the reliability of the established test method was further validated in three intra assays. Here, the correlation coefficient of $R^2$>0.99, the slope of -3.10 ~ -3.40, and the recovery rate within ${\pm}20%$ of the siRNA standard curve confirm its excellent robustness. Finally, the circulation profiles of siRNAs were demonstrated in rat serum, and the pharmacokinetic properties of the anti-HPV E6/E7 siRNA therapeutic were characterized using a stem-loop RT-qPCR assay. Therefore, the stemloop RT-qPCR assay enables accurate, precise, and sensitive siRNA duplex quantification and is suitable for the quantification of small RNA therapeutics using small volumes of biological samples.

The Effects of Isopropyl 2-(1,3-dithioetane-2-ylidene)-2-[N-(4-methyl-thiazol-2-yl)carbamoyl]acetate (YH439) on Potentiated Carbon Tetrachloride Hepatotoxicity (상승적 화학적 간독성에 미치는 YH439의 영향)

  • Kim, Sang-Geon;Cho, Joo-Youn
    • The Korean Journal of Pharmacology
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    • v.32 no.3
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    • pp.407-416
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    • 1996
  • The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

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