• Title/Summary/Keyword: mixed-function oxidase system

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Effects of Calorie Restriction on Microsomal Mixed Function Oxidase System and Free Radical in Kidney of SAMP8 Mice

  • kim, Hyun-Jeong;Choi, Jin-Ho;Rhee, Soon-Jae
    • Nutritional Sciences
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    • v.7 no.4
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    • pp.189-195
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    • 2004
  • 1bis study investigated the antioxidative effect in kidney of senescence-accelerated prone SAMP8 mice with calorie restriction. 4-weeks-old SAMP8 female mice were divided into 4 groups according to the experimental feeding period: for 4, 8, 12 month, and at natural death. Each group was subdivided into 2 groups, with thirteen mice each one, as ad libitum group and as dietary restriction group (60% of ad libitum feeding amount). After feeding for a given period, the mice were sacrificed to get the following results: among the experimental groups, there wereno significant differences in xanthine oxidase (XOD) activity in their kidney tissues. The contents of cytochrome $P_{450}$ decreased in ad libitum group and dietary restriction group by age. The activity of NADPH-cytochrome $P_{450}$ reductase showed a trend similar to cytochrome $P_{450}$. Superoxide radical content increased with age. At the 4th, 8th and 12 months of the experimental period, the activity in the dietary restriction group was less than that of ad libitum group by as much as 17% 14% and 14% respectively. For hydrogen peroxide, the contents were increased in the ad libitum group with age, while no correlation between content and age was observed in the dietary restriction group. In the 8th and 12th months of the experimental period, the were in the dietary restriction group less than that of ad libitum group counterpart as much as 17% and 20o/c, respectively. For the cellular membrane stability of the kidney, no significant correlation with age was observed in either the dietary restriction group or the ad libitum group. However at the 12th month of the experiment, however, the stability in the dietary restriction group was 11 % higher than that in the ad libitum group. In conclusion, with these results obtained from the SAMP8 mouse model, we demonstrate that dietary restriction has the effects of anti-oxidation and anti-senescence in the kidney.

Toxic action of N-dimethylphosphinothioyl carbofuran by oxidative activation process (산화적 활성화 과정을 통한 N-dimethoxyphosphinothioyl carbofuran의 독성발현)

  • Yang, Kyew-Wan;Lee, Seog-Jong;Kim, Song-Mun;Han, Dae-Sung;Hur, Jang-Hyun
    • The Korean Journal of Pesticide Science
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    • v.2 no.2
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    • pp.10-15
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    • 1998
  • The bimolecular inhibition rate constants of carbofuran and N-dimethylphosphinothioyl carbofuran(PSC) to acetylcholinesterase(AChE) were $7.7{\times}10^{5}\;M^{-1}{\cdot}min^{-1}$ and $1.2{\times}10^{3}\;M^{-1}{\cdot}min^{-1}$, respectively. These results showed that PSC required a bioactivation process for its toxic action because it didn't inhibit the target enzyme effectively. The potency of PSC as an inhibitor of AChE increased when PSC and AChE were incubated with microsomes fortified with NADPH compared with microsome alone. Piperonyl butoxide(PBO) addition to these coupled systems greatly reduced the inhibition of the target enzyme by blocking the bioactivation process. In vivo inhibition study of mouse brain AChE, $I_{50}$ value for AChE was 28 mg/kg for PSC and the value increased to 57 mg/kg when PBO was pretreated. This result showed that cytochrome $P_{450}$ would also play a role in the bioactivation process of PSC in vivo. And conversioin of carbofuran from PSC was 55 % in a chemical oxidation system using meta-chloroperoxybenzoic acid. The oxidative activation of PSC to carbofuran was shown to be essential for showing its toxicological action and cytochrome $P_{450}$ was identified as an important enzyme which participated in this process.

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In vitro and in vivo Responses of MFO Systems in Olive Flounder (Paralichthys olivaceus) Exposed to TBT and TPT for Short-term Period (유기주석화합물에 단기간 노출시킨 넙치 간장 약물대사효소의 in vivo 및 in vitro 반응)

  • 전중균;이지선;전미정;심원준;임한규
    • Korean Journal of Environmental Biology
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    • v.22 no.1
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    • pp.177-183
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    • 2004
  • Cytochrome P45O (CYP) contents and 7-ethoxyresorufin-O-deethylase (EROD) activity were determined in hepatic microsome of olive flounder (Paralichthys olivaceus) exposed to tributyltin chloride (TBTC), tributyltin oxide (TBTO), and triphenyltin chloride (TPTC). In addition, effects of in vivo (intraperitoneal injection of 7.5 mg $kg^{-1}$ BW) exposure of flounder to TPTC on CYP, NADPH cytochrome c reductase, NADH cytochrome b5 yeductase and EROD levels were measured. In in vitro exposure of hepatic microsome to organotins, TBTC, TBTO and TPTC reduced CYP contents and inhibited EROD activity. The TPTC was the strongest inhibitor, which is followed by TBTO and TBTC. The degree of inhibition, especially EROD acitivity, depended on the exposure duration. In addition, all the target enzymes in flounder were inhibited by TPTC with the in vivo exposure to TPTC. As EROD activity was the most sensitive to the inhibitions and demonstrated good reproducibility of the results, it could be used as a helpful tool toy monitor effects of organotin compounds on mixed funciton oxygenase system in marine fish.

Study of the possible mode of action of O-ethyl S-methyl ethylphosphonothioate via the formation of S-oxide in chemical and metabolic oxidation systems (화학적, 대사적 산화반응 중 생성되는 S-oxide를 이용한 O-ethyl S-methyl ethylphosphonothioate (1) 의 독성 기작에 관한 연구)

  • Hur, J.H.;Fukuto, T.R.;Han, D.S.
    • Korean Journal of Environmental Agriculture
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    • v.10 no.2
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    • pp.167-177
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    • 1991
  • O-ethyl S-methyl ethylphosphonothioate [$LD_{50}$ (rat, oral) 4.6mg/kg ; $K_i$(bovine erythrocyte acetylcholinesterase) 303 $M^{-1\;min-1}$] was selected as a model compound to study the mode of action of O, S-dialkyl alkylphosphonothioates which have been hypothesized to be toxic via a bioactivation process. Two chemical oxidants, meta-chloroperoxybenzoic acid and monoperoxyphthalic acid, and rat liver microsomal oxidases were used to mimic the action of mixed function oxidases on the model compound. The formation of S-oxide, a very unstable active intermediate, was proposed based on the identification of metabolic products.Furthermore, a trapping experiment with ethanol showed that the unstable intermediate S-oxide had the ability to phosphorylate acetylcholinesterase which is an important enzyme in nerve systems. The S-oxide intermediates are presumed to be responsible for the toxicity of O,S-dialkyl alkylphosphonothioates.

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