• Applied Biological Chemistry
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• 제37권3호
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• pp.194-202
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• 1994

$^{14}C-{\alpha}-endosulfan$을 공시어인 잉어(Cyprinus carpio L.)에 대해서 $LC_{10}$ 농도$(4.5\;{\mu}g/L)$로 처리하여 in vivo 대사과정을 추적한 결과 endosulfan은 처리 직후에 공시어에 빠르게 흡수되었다가 시간이 경과됨에 따라 잉어체내로부터 제거되었다. 잉어의 간과 신장, 소화관에서 발견된 endosulfan의 대사물질로는 EE(endosulfan ether), EA(endosulfan alcohol), EHE(endosulfan hydroxyether), EL(endosulfan lactone)이었으며 주된 대사물질은 EE와 EA이었다. 다만 식물체와 포유류 등에서 발견되는 것으로 알려진 ES(endosulfan sulfate)는 공시어의 어느 조직에서도 발견되지 않았다. $^{14}C-endosulfan$의 공시어 머리와 근육, 소화관에서의 흡수는 처리 8시간 후에 최대에 이르렀으나 간과 신장에서는 각각 처리 30분과 4시간 후에 최대의 흡수량을 보였다. 공시어의 모든 조직에서 방사능량은 처리 8시간 후에는 급격히 감소하였으며 이때 간, 신장, 소화관 조직에서 $^{14}C-endosulfan$의 회수율은 $80{\sim}90%$로 나타났다. 하지만 처리 8시간이 경과한 이후부터는 추출되지 않은 방사능량이 증가$(27{\sim}31%)$되었으며 8시간을 중심으로 수용성 물질의 생성이 증가되었다.

• Asian-Australasian Journal of Animal Sciences
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• 제26권6호
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• pp.879-885
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• 2013

Fifty-four, mixed-sex, halothane-carrier crossbred (Yorkshire${\times}$Landrace) pigs with an average initial BW of $108.2{\pm}0.8$ kg were randomly allotted to one of three dietary treatments for 5 d before slaughter: i) a control corn-soybean meal finisher diet devoid of supplemental magnesium; ii) a diet supplemented with 1.5 g/kg of elemental Mg from magnesium acetate; and iii) a diet supplemented with 1.5 g/kg of elemental Mg from magnesium sulfate heptahydrate. Serum creatine kinase (CK), lactate and glucose were analyzed at slaughter. Muscles from longissimus (LM) were packaged and stored to simulate display storage for muscle lactate and glycogen determinations at 0, 1, 2, 3, and 4 d. Mg supplementation reduced (p<0.05) serum CK and lactate concentration, but had no effect (p>0.05) on serum glucose. Daily change of muscle lactate concentration linearly increased (p<0.01), while glucose concentration linearly decreased (p<0.05) as storage time increased in all treatments. However, dietary Mg acetate and Mg sulfate supplementation in pigs elevated (p<0.05) muscle glycogen and reduced (p<0.05) muscle lactate concentrations, especially during the first 2 d of display, compared with pigs fed the control diet. This study suggests that short-term feeding of magnesium acetate and magnesium sulfate to heterozygous carriers of the halothane gene has beneficial effects on stress response and pork quality by improving blood and muscle biochemical indexes.

• Biomolecules & Therapeutics
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• 제30권6호
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• pp.510-519
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• 2022

Tofacitinib, a Janus kinase 1 and 3 inhibitor, is mainly metabolized by CYP3A1/2 and CYP2C11 in the liver. The drug has been approved for the chronic treatment of severe ulcerative colitis, a chronic inflammatory bowel disease. This study investigated the pharmacokinetics of tofacitinib in rats with dextran sulfate sodium (DSS)-induced ulcerative colitis. After 1-min of intravenous infusion of tofacitinib (10 mg/kg), the area under the plasma concentration-time curves from time zero to time infinity (AUC) of tofacitinib significantly increased by 92.3%. The time-averaged total body clearance decreased significantly by 47.7% in DSS rats compared with control rats. After the oral administration of tofacitinib (20 mg/kg), the AUC increased by 85.5% in DSS rats. These results could be due to decreased intrinsic clearance of the drug caused by the reduction of CYP3A1/2 and CYP2C11 in the liver and intestine of DSS rats. In conclusion, ulcerative colitis inhibited CYP3A1/2 and CYP2C11 in the liver and intestines of DSS rats and slowed the metabolism of tofacitinib, resulting in increased plasma concentrations of tofacitinib in DSS rats.

• Nutrition Research and Practice
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• 제16권2호
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• pp.147-160
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• 2022

BACKGROUND/OBJECTIVES: Patients with chronic kidney disease (CKD) have a high concentration of uremic toxins in their blood and often experience muscle atrophy. Indoxyl sulfate (IS) is a uremic toxin produced by tryptophan metabolism. Although an elevated IS level may induce muscle dysfunction, the effect of IS on physiological concentration has not been elucidated. Additionally, the effects of ursolic acid (UA) on muscle hypertrophy have been reported in healthy models; however, it is unclear whether UA ameliorates muscle dysfunction associated with chronic diseases, such as CKD. Thus, this study aimed to investigate whether UA can improve the IS-induced impairment of mitochondrial biogenesis. MATERIALS/METHODS: C2C12 cells were incubated with or without IS (0.1 mM) and UA (1 or 2 μM) to elucidate the physiological effect of UA on CKD-related mitochondrial dysfunction and its related mechanisms using real-time reverse transcription-polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. RESULTS: IS suppressed the expression of differentiation marker genes without decreasing cell viability. IS decreased the mitochondrial DNA copy number and ATP levels by downregulating the genes pertaining to mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam, Sirt1, and Mef2c), fusion (Mfn1 and Mfn2), oxidative phosphorylation (Cycs and Atp5b), and fatty acid oxidation (Pdk4, Acadm, Cpt1b, and Cd36). Furthermore, IS increased the intracellular mRNA and secretory protein levels of interleukin (IL)-6. Finally, UA ameliorated the IS-induced impairment in C2C12 cells. CONCLUSIONS: Our results indicated that UA improves the IS-induced impairment of mitochondrial biogenesis by affecting differentiation, ATP levels, and IL-6 secretion in C2C12 cells. Therefore, UA could be a novel therapeutic agent for CKD-induced muscle dysfunction.

• Toxicological Research
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• 제13권1_2호
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• pp.117-125
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• 1997

In order to assess the possibility whether CYP2D is involved in caffeine metabolism, we have purified and characterized the rat liver microsomal cytochrome P4502D1 (CYP2D1), equivalent to CYP2D6 in human liver, and have utilized the reconstituted CYP2D1 in the metabolism of 4 primary caffeine (1, 3, 7-trimethylxanthine) metabolites such as paraxanthine (1, 7-dimethylxanthine), 1, 3, 7-trimethylurate, theophylline (1, 3-dimethylxanthine) and theobromine (3, 7-dimethylxanthine). Rat liver CYP 2D1 has been purified to a specific content of 8.98 nmole/mg protein (13.4fold purification, 1.5% yield) using $\omega$-aminooctylagarose, hydroxlapatite, and DE52 columns in a sequential manner. As judged from sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), the purified CYP2D1 was apparently homogeneous. Molecular weight of the purified CYP2D1 was found to be 51, 000 Da. Catalytic activity of the purified and then reconstituted CYP2D1 was confirmed by using bufuralol, a known subsFate of CYP2D1. The reconstituted CYP2D1 was found to produce to 1-hydroxylbufuralol at a rate of 1.43$\pm$0.13 nmol/min/nmol P450. The kinetic analysis of bufuralol hydroxylation indicated that Km and Vmax values were 7.32$\mu M$ and 1.64 nmol/min/nmol P450, respectively. The reconstituted CYP2D1 could catalyze the 7-demethylation of PX to 1-methylxanthine at a rate of 12.5 pmol/min/pmol, and also the 7- and 3- demethylations of 1, 3, 7-trimethylurate to 1, 3-dimethylurate and 1, 7-dimethylurate at 6.5 and 12.8 pmol/min/pmol CYP2D1, respectively. The reconstituted CYP2D1 could also 3-demethylate theophylline to 1-methylxanthine at 5 pmol/min/pmol and hydroxylate the theophylline to 1, 3-dimethylurate at 21.8 pmol/min/pmol CYP2D1. The reconstituted CYP2D1, however, did not metabolize TB at all (detection limits were 0.03 pmol/min/pmol). This study indicated that CYP2D1 is involved in 3-and 7-demethylations of paraxanthine and theophylline and suggested that CYP2D6 (equivalent to CYP2D1 in rat liver) present in human liver may be involved in the secondary metabolism of the primary metabolites of caffeine.

• 약학회지
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• 제42권4호
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• pp.422-430
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• 1998

In order to study the effects of Rhei rhizoma, Ephedrae herba and Scutellariae radix on hepatic metabolism, we examined the pretreatment effect of those on the metabolism of 7-e thoxycoumarin (EC). Water extracts (1g/kg) of Rhei rhizoma, Ephedrae herba and Scutellariae radix were administered orally to rats for 7 days, respectively. Livers were then isolated and perfused with 100mcM EC for 2 hours. The metabolites of EC, 7-hydroxycoumarin, sulfate conjugate and glucuronide conjugate were measured in the perfusates. The amount of glucuronide conjugates was decreased in Rhei rhizoma pretreated rats (p<0.01), however, 7-hydroxycoumarin was increased in Ephedrae herba pretreated rats (p<0.01). We examined whether the change of enzyme activity is related to the change of cytochrome P4501A1 and P4502B1 mRNA level in the perfused rat liver, which are responsible for EC metabolism. CYP1A1 and CYP2B1 mRNA level was increased, which was was not statistically significant with rhei rhizoma nor ephedrae herba pretreatment. We also assessed the hepatotoxicity of Rhei rhizoma, Ephedrae herba and Scutellariae radix. The activities of ALT and AST were assayed at 24 hours after 7 days administration. Only the ratio of ALT over AST was increased in ephedrae herba pretreated rats (p<0.05). Lipid peroxidation was increased in Rhei rhizoma treatment (p<0.05), while histopathological examination performed after liver perfusion did not show any difference compared with vehicle treatment. These results suggest that Ephedrae herba pretreatment increases the o-deethy-lation of 7-ethoxycoumarin in rats, which may be mediated by CYP1A1 mRNA induction.

• Journal of Interdisciplinary Genomics
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• 제2권2호
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• pp.20-25
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• 2020

Mucopolysaccharidosis type III (MPS III or Sanfilippo syndrome) is a multisystem lysosomal storage disease that is inherited in an autosomal recessive manner. It consists of four subtypes (MPS IIIA, B, C, and D), each characterized by the deficiency of different enzymes that catalyze the metabolism of the glycosaminoglycan heparan sulfate at the lysosomal level. The typical clinical manifestation of MPS III includes progressive central nervous system (CNS) degeneration with accompanying systemic manifestations. Disease onset is typically before the age of ten years and death usually occurs in the second or third decade due to neurological regression or respiratory tract infections. However, there is currently no treatment for CNS symptoms in patients with MPS III. Invasive and non-invasive techniques that allow drugs to pass through the blood brain barrier and reach the CNS are being tested and have proven effective. In addition, the application of genistein treatment as a substrate reduction therapy is in progress.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2001년도 추계학술발표대회
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• pp.545-548
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• 2001

Microbiologically influenced corrosion (MIC) of metal is common in the natural environment and sulfate reducing bacteria are representative microorganisms for MIC. We found that biofilm fomlation by SRB on the metal surface might be controlled by quorum sensing, which is a cell density dependent regulation of cell metabolism. As cell free culture fluids (spent media) of Desulfovibrio vulgaris and D. desulfuricans were tested for quontrn sensing related test strains, it was found that spent media of two SRB induced increased luminescence of Vibrio harveyi BB886 (sensor 1+, sensor 2-) and BB170 (sensor 1-, sensor 2+). Quorum activities of D. vulgaris and D. desulfuricans appeared to be parallel to growth patterns, i.e., it was low in the lag phase, highly increased in the exponential phase, and reached maximum in the stationary phase. Interestingly, however, luminescence of V. harveyi BB886 and BB170 induced by a unit cell mass of the SHB showed a maximal peak in the late lag phase. Hence, it was suspected that quorum sensing of these two SHB play unknown roles in shifting cells from dormant to growth stages.

• 대한수의학회지
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• 제25권2호
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• pp.145-148
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• 1985

Nickel toxicity and interactions of nickel with zinc, copper, and lead were studied in glowing chicks fed supplemented diet. Feed intake and growth rate of the chick were reduced by 250mg nickel as a sulfate salt per kg of feed. The toxicity of nickel was decreased by zinc or copper supplementation, but not lead. High nickel feed increased nickel level in kidney and decreased zinc levels in tibia and plasma. However, low zinc levels in tibia and in plasma were reversed by zinc supplementation. Hemoglobin, packed cell volume, and aortic elastin content were increased in chicks fed nickel. These results suggest that nickel toxicity is induced by interference with zinc metabolism.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.248.1-248.1
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• 2003

Glucocorticoids are used most widely for the treatment of inflammatory bowel disease (IBD). For the efficient treatment and reduction of side effects, colon-specific delivery of a glucocorticoid is highly desirable. Previously, we synthesized prednisolone 21-sulfate sodium (PDS) as a colon-specific prod rug of prednisolone (PD) expecting that it might be stable and nonabsorbable in the upper intestine and hydrolyze in the colon to release PD. (omitted)