• 제목/요약/키워드: SKF 525A

검색결과 15건 처리시간 0.021초

자성 흰쥐의 파라치온 급성독성 및 대사에 미치는 페노바르비탈 및 SKF-525-A의 영향 (EFFECT OF PHENOBARBITAL AND / OR SKF 525-A ON THE METABOLISM AND ACUTE TOXICITY OF PARATHION IN ADULT FEMALE PATS)

  • 최재화;임혜경;김영철
    • Toxicological Research
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    • 제6권1호
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    • pp.51-59
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    • 1990
  • Effects of altering hepatic mixed-function oxidase (MFO) enzyme activities on the metabolism and acute toxicity of parathio were investigated in adult female rats. In vitro hepatic metabolism of parathion to paraoxon was increased by phenobarbital pretreatment (50 mg/kg/day, ip, for 4 consecutive days) and SKF 525-A (50 mg/kg, ip, 1 hr prior to sacrifice) decreased paraoxon formation indicating that phenobarbital induces that form(s) of cytochrome P-450 catalyzing conversion of parathion to paraoxon. Degradation of paraoxon to p-nitrophenol was increased by phenobarbital pretreatment, but not affected by SKF 525-A suggesting that MFO activities play only a minor role in the detoxification of the active metabolite of this insecticide. The phenobarbital-induced increase in paraoxon formation was partially antagonized by SKF 525-A. Significant activity for both parathion activation and paraoxon degradation was also observed in the lung preparation, however, this extrahepatic parathion and paraoxon metabolizing activity was not induced by phenobarbital or inhibited by SKF 525-A pretreatment. Phenobarbital pretreatment increased paraoxon level in livers of rats when measured 3 hr following parathion injection (2 mg/kg, ip). SKF 525-A did not alter parathion or paraoxon levels in brain, blood and liver. Phenobarbital pretreatment decreased the toxicity of parathion (4mg/kg, ip) or paraoxon (1.5 mg/kg, ip) as determined by decreases in lethality and inhibition of brain and lung acetylcholinesterases. An additional SKF 525-A treatment failed to decrease the protective effects of phenobarbital against parathion or paraoxon toxicity. These results suggest that some unknown factors other than hepatic MFO induction are involved in the protective action of phenobarbital against parathion and paraoxon toxicity.

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SKF 525A가 휜쥐의 대동맥에서 Sodium nitroprusside, Acetylcholine, Pinacidil에 의한 이완반응에 미치는 효과 (The effect of SKF S25A on SNP-, Ach-, or Pinacidil-Induced Relaxation in the Aorta of Rat)

  • 박조영;김학림;김주원;신창열;최윤미;김진학;안형수;손의동;허인회
    • 약학회지
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    • 제44권1호
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    • pp.80-86
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    • 2000
  • TEA, glibenclamide, L-NAME and SKF 525A-induced contraction were investigated using acetylcholine, sodium nitroprusside (SNP, NO donor) and pinacidil (ATP sensitive $K^{+}$ channel opener) in rat abdominal and thoracic aorta. The relaxant effects of acetylcholine, SNP and pinacidil were not different in the abdominal aorta and in the thoracic aorta. Acetylcholine-induced relaxation was dependent on endothelial cell, but pinacidil was independent endothelia cell. In the presence of TEA, glibenclamide, L-NAME, mepacrine and SKF 525A, acetylcholine and SNP did not change, but pinacidil-induced relaxation was significantly reduced in presence of glibenclamide, which is ATP sensitive $K^{+}$ channel blocker. SKF 525A, which is inhibitor of cytochrome P$_{450}$ dependent epoxygenase, partially inhibited the pinacidil-induced relaxation. These results indicate that the pinacidil-induced relaxation may be mediated by ATP sensitive $K^{+}$ channel and partially by EETs, which is produced by cytochrome P$_{450}$ dependent epoxygenase.enase.

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흰쥐의 대동맥 이완반응에 대한 재수축효과 (The Reversible Contraction on Relaxation of Isolated Rat Aorta)

  • 김진학;신창열;박조영;민영실;최경범;염지현;이남인;김학림;손의동
    • Biomolecules & Therapeutics
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    • 제8권2호
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    • pp.113-118
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    • 2000
  • TEA, glibenclamide, L-NAME and SKF 525A-induced reversible contraction were investigated using acetylcholine, sodium nitroprusside (SNP) and pinacidil in rat abdominal and thoracic aorta. Acetylcho-line, SNP or pinacidil produced in a dose dependent manner relaxation on phenylephrine-induced contraction In rat aorta. TEA, SKF 525A, and L-NAME produced reversible contractions on acetylcholine-induced relaxation, but not on SNP- or pinacidil-induced relaxation. Glibenclamide significantly produced reversible con- traction on pinacidll-induced relaxation. The reversible effect of TEA on the acetylcholine-induced relaxation was reduced by SKF 525A. These results indicate that the acetylcholine-induced relaxation may be mediated by NO, cytochrome P$_{450}$-dependent epoxygenase pathway, or $Ca^{2+}$ activated $K^{+}$ channel, and the pinacidil-induced relaxation may be mediated by ATP-sensitive $K^{+}$ channel.annel.

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Sodium Phenobarbitone 및 β-Diethylaminoethyl Diphenylpropyl Acetate (SKF 525 A)가 Ngaione에 중독(中毒)된 흰쥐의 간장병변(肝臟病變)에 미치는 영향(影響) (Effect of Sodium Phenobarbitone and β-Diethylaminoethyl Diphenylpropyl Acetate(SKF 525 A) on the Liver Lesions Caused by a Single Intraperitoneal Dose of Ngaione in the Rat)

  • 이준섭
    • 대한수의학회지
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    • 제14권2호
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    • pp.215-219
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    • 1974
  • Ngaione isolated from leaves of Myoporum deserti was dosed to the phenbarbitone and SKF 525 A pretreated male rat and studied the liver lesions. The results obtained were summarized as follows: 1. The liver lesions are mostly zonally distributed and involved the midzonal parenchyma chiefly with tendence to include also associated periportal hepatocytes. 2. The histopathology of liver due to ngaione after phenoharbitone pretreatment is characterized by the consistent pretence of degeneration and necrosis of the periportal parenchyma. 3. Zonal liver lesions caused by ngaione in the SKF 525 A pretreated rat are consistently periacinar in location.

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A Comparison of the In Vitro Inhibitory Effects of Thelephoric Acid and SKF-525A on Human Cytochrome P450 Activity

  • Song, Min;Do, HyunHee;Kwon, Oh Kwang;Yang, Eun-Ju;Bae, Jong-Sup;Jeong, Tae Cheon;Song, Kyung-Sik;Lee, Sangkyu
    • Biomolecules & Therapeutics
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    • 제22권2호
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    • pp.155-160
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    • 2014
  • Thelephoric acid is an antioxidant produced by the hydrolysis of polyozellin, which is isolated from Polyozellus multiplex. In the present study, the inhibitory effects of polyozellin and thelephoric acid on 9 cytochrome P450 (CYP) family members (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) were examined in pooled human liver microsomes (HLMs) using a cocktail probe assay. Polyozellin exhibited weak inhibitory effects on the activities of all 9 CYPs examined, whereas thelephoric acid exhibited dose- and time-dependent inhibition of all 9 CYP isoforms ($IC_{50}$ values, $3.2-33.7{\mu}M$). Dixon plots of CYP inhibition indicated that thelephoric acid was a competitive inhibitor of CYP1A2 and CYP3A4. In contrast, thelephoric acid was a noncompetitive inhibitor of CYP2D6. Our findings indicate that thelephoric acid may be a novel, non-specific CYP inhibitor, suggesting that it could replace SKF-525A in inhibitory studies designed to investigate the effects of CYP enzymes on the metabolism of given compounds.

THE EFFECTS OF ALTERING THE HEPATIC DRUG METABOLIZING ENZYME ACTIVITY ON THE ACUTE TOXICITY OF DIETHYL-4-NITROPHENYL PHOSPHOROTHIOATE (PARATHION) IN FEMALE RATS1.

  • Kim, Young-Chul;Park, Jae-Hwa;Lim, Hye-Kyung
    • Toxicological Research
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    • 제4권2호
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    • pp.107-115
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    • 1988
  • The effects of altering the hepatic mixed-function oxidase(MFO) activities on the acute toxicity of parathion were examined in female rats. Phenobarbital sodium pretreatment (50mg/kg/day, i.p.) for 4 consecutive days has resulted in significant decreases in the toxicity of parathion (2 or 4 mg/kg, i.p.) as determined by lethality and cholinesterase activities wheras the toxicity arising from a single dose of CCl4(2 mmol/kg, i.p.) 24 hr prior to parathion challenge was potentiated.

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Antiestrogen등 약물이 cytochrome P450와 AEBS에 미치는 효과의 관계

  • 신윤용;정세영
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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    • pp.100-100
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    • 1993
  • Antiestrogen은 에스트로젠 의존성 유방암 치료에 사용되는 약물로써 표적 세포 내에서 에스트로젠 수용체와 작용하여 세포 증식 억제 작용을 나타내고 동시에 에스트로젠 수용체와는 구분되는 소포체 분획의 antiestrogen specific binding site (AEBS) 와도 결합을 하는 것으로 알려져 있다. 그러나, 아직 이 AEBS의 생리적 또는 약리적 기능은 밝혀져 있지 않다. 따라서 본 실험에서는 AEBS의 기능을 조사하기 위하여 cytochrome P45O III 효소군과 AEBS와의 관계를 자옹 백서를 이용하여 면역 화학 반응 실험 및 경쟁적 결합 반응 실험을 하였고, 그 결과는 다음과 같다. 1) AEBS에 대해서 SKF-525A와 metyrapone은 결합 능력을 나타내었다. 2) 자성쥐에서는 주령이 증가함에 따라 cytochrome P450양이 감소하였다. 3) 자옹성쥐 모두에서 phenobarbital 처치에 의해 cytochrome P450 III 효소양이 증가하였고, AEBS도 증가하였다. 4) 웅성쥐에서는 testosterone에 의하여 AEBS가 증가하였다. 5) 자웅성쥐 모두에 tamoxifen 관류시 cytochrome P450 III 효소양이 증가하였고 estradiol과 병용 관류시에는 tamonifen 단독 관류시보다 감소하였다. 이상의 결과에서 tamoxifen이 cytochrome P450 III을 유도할 수 있는 것으로 사료되며 cytochrome P450 III 효소군과 안티에스트로젠 결합부위와 밀접한 관련이 있는 것으로 생각된다.

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해면체에서 추출한 Pectenotoxin 2의 마우스에서의 반복적인 투여에 의한 독성 및 간대사효소계에 주는 영향 (Toxicity and Changes in Hepatic Metabolizing Enzyme System Induced by Repeated Administration of Pectenotoxin 2 Isolated from Marine Sponges)

  • 윤미영;김영철
    • 생약학회지
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    • 제28권4호
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    • pp.280-285
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    • 1997
  • Pectenotoxin 2 (PTX2), isolated from marine sponges, was examined for its hepatotoxic potential using male ICR mice. PTX2 $(20\;or\;100\;{\mu}g/kg/day,\;ip)$ was administered to mice repeatedly for one or two week. Histopathological examination revealed an increase in granularity in the liver from the mice treated with PTX2. PTX2 did not alter the parameters for hepatotoxicity and nephrotoxicity such as sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Cytochrome P-450, cytochrome $b_5$, or NADPH cytochrome c reductase was net changed by repeated administration of PTX2. Hepatic microsomal activity of p-nitroanisole O-demethylase, but not aminopyrine N-demethylase, was slightly depressed by PTX2 administerd repeatedly $(100\;{\mu}g/kg/day,\;ip)$ fur 2 weeks. The toxicity of PTX2 $(200\;{\mu}g/kg/day,\;ip)$ was determined in mice pretreated with a metabolic inducer or inhibitor such as phenobarbital, 3-methyl-cholanthrene, $CoCl_2$, or SKF 525-A. Significant alterations in lethality and hepatotoxicity of PTX2 were observed in mice pretreated with a metabolic modulator. The results suggest that liver seems to be the target organ for PTX2 toxicity and also that induction of the PTX2 toxicity may be associated with hepatic drug metabolizing activity.

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Polychlorinated biphenyl 전처리한 횐쥐 간장의 S-9 분획에서 Stanozolol의 Hydroxylation 대사체의 생성 (In vitro Metabolism of Stanozolol to 3'-Hydroxystanozolol in the Liver S-9 Fraction of Polychlorinated Biphenyl-treated Rats)

  • 권오승;류재천
    • 약학회지
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    • 제44권5호
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    • pp.379-383
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    • 2000
  • Stanozolol (STZ, 17$\alpha$-methyl-17$\beta$-hydroxy-5$\alpha$-androstano-(3,2-c) pyrazole), an anabolic steroid, is an abused drug by body-builders or atheletes, as well as medicine for treatment of aplastic anemia and vascular thrombosis. In human volunteers, the major urinary metabolite of STZ was reported to be 3'-hydroxystanozolol that was identified by gas chromatography-mass selective detector (GC/MSD). The objective of this experiment is to investigate the in vitro metabolism of STZ in liver S-9 faction of polychlorinated biphenyl-induced rats. Reaction mixture including STZ as substrate and the S-9 faction was extracted with diethyl ether and quantified by the selected ion monitoring mode of GC/MSD. The selected concentration of substrate STZ is 100 nmole and the selected time for incubation in the reaction mixture was determined to 60 min. The amount of 3'-hydroxystanozolol produced was increased by about 6-fold in the reaction medium including the liver S-9 fraction of polychlorinated biphenyl-induced rats, compared to that of untreated rats. Inhibitors of cytochrome P450, SKF-525A and 7,8-benzoflavone, decreased the production of 3'-hydroxystanozolol by about 89~100% and 65~75%, respectively; In conclusion, hydroxylation of STZ into 3'-hydroxystanozolol is confirmed by GC/MSD and is catalyzed by cytochrome P450.

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Protein kinase A 억제제인 KT5720이 글루카곤 매개성 항산화 효소의 발현감소에 미치는 영향 (Effects of the Protein Kinase A Inhibitor KT5720 on Glucagon-Mediated Decrease in Expression of Antioxidant Enzymes)

  • 오수진;조재훈;박창식;김상겸;김봉희
    • Environmental Analysis Health and Toxicology
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    • 제21권3호
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    • pp.245-253
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    • 2006
  • We reported previously that glucagon decreased alpha- and pi-class glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEN) protein levels in primary cultured rat hepatocytes. The present study examines the effects of Protein kinase A (PKA) inhibitor, KT5720, on the glucagon-mediated decrease in expression of GSTs and mEN. To assess cell viability. lactate dehydrogenase release and MTT activity were examined in hepatocytes treated KT5720. Cell viability was significantly decreased in a concentration dependent manner after incubation with KT5720 at the concentrations of 1 $\mu$M or above for 24 h, which was inhibited by the cytochrome P450 inhibitor SKF-525A. In contrast, another PKA inhibitor H89 (up to 25 $\mu$M) was not toxic to hepatocytes. The glucagon-mediated decrease in expression of alpha- and pi-class GSTs and mEH was completely inhibited by 25 $\mu$M H89 and attenuated by 0.1 $\mu$M KT5720. This study demonstrates that KT5720 may cause cytotoxicity in rat hepatocytes through cytochrome P450-dependent bioactivation. The present study implicates PKA in mediating the inhibitory effect of glucagon on expression of alpha- and pi- class GSTs and mEH.