• Fisheries and Aquatic Sciences
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• 제5권1호
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• pp.28-31
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• 2002

Effects of cimetidine, a cytochrome P450 inhibitor, on the benzo[a]pyrene (BaP)-mediated cytochrome P450 induction and lipid peroxidation of liver in olive flounder, Paralichthys olivaceus, were investigated. Fish were fed either a cimetidine-supplemented diet or a cimetidine-free control diet once daily to satiation for 3 days. After 6 hrs of last feeding, the fish received intraperitoneal (i.p.) injection of BaP (20 mg/kg of body weight) dissolved in sterile corn oil $(100 \mu L)$ or received only a corn oil i.p. injection. At 1, 2, 3, and 7 days after the injection, hepatic cytochrome P450 and thiobarbituric acid reactive substances (TBARS), an indicator of lipid peroxidation, were analyzed. BaP injection resulted in an increase of hepatic cytochrome P450, and the fish fed the cimetidine-supplemented diet before injection of BaP showed delayed increase of hepatic cytochrome P450 compared to the fish fed a cimetidine-free diet and BaP injected. Injection of BaP clearly induced hepatic lipid peroxidation, and consistently higher TBAR values were shown in the fish fed a cimetidine­supplemented diet before injection of BaP than the fish injected with BaP alone.

• 한국미생물·생명공학회지
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• 제24권5호
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• pp.591-596
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• 1996

In the course of screening lipid peroxidation inhibitor from basidiomycetes, a mushroom, which was collected at O-Dae mountain in Kangweon- Do, was found to have active compound. The mushroom was identified as Polyzellus multiplex, which belongs to Aphylloporalles Thelephoraceae, on the basis of macroscopic and microscopic characteristics of the fruiting body. The methanol extract of fruiting body was extracted with benzene and ethylacetate, sequentially. By using various kinds of chromatographies, PM1, and PM2 and PM3, were purified from the ethylacetate extract and the benzene extract, respectively. Color reaction and analyses of IR, UV, and NMR spectra indicated that PM1 was a derivative of thelephoric acid, and PM2 and PM3 were linoleic acid and oleic acid, respectively. IC$_{50}$ of PM1 for inhibition of lipid peroxidation was 1.96 ppm and LD$_{50}$ was 500 mg/kg.

• 한국미생물·생명공학회지
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• 제26권6호
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• pp.558-561
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• 1998

식용버섯인 버들송이(Agrocybe cylindracea)로부터 새로운 생리활성물질을 탐색하던 중 버들송이 자실체의 methanol 추출물로부터 Diaion HP-20 column chromatography, ethyl acetate extraction 및 silica gel column chromatography를 행하여 AG 8을 분리하였다. 분리된 AG 8의 구조해석을 위하여 Mass, $^1$H 및 $^{13}$C NMR, irradiation실험 및 HMBC를 실시한 결과 분자량이 297, 분자식이 $C_{11}$ $H_{15}$$N_{5}$$O_3$S인 nucleoside계 화합물 5'-deoxy-5'-methylthioadenosine(MTA)으로 동정하였다. AG 8의 지질과산화 저해활성은 $IC_{50}$/ 값이 3.2 $\mu\textrm{g}$/$m\ell$ 이었으며 양성 대조구인 vitamin E보다 3배 정도 낮은 활성을 보여주었다. 본 화합물은 고등동물의 대사과정에 관여하는 효소 대사 조절물질로 고등동물을 비롯한 각종 생물체에 존재하는 것이 보고되었으나 담자균류로부터는 본 연구에 의하여 처음 분리되었다.

• 생약학회지
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• 제31권3호
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• pp.264-267
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• 2000

Anti-human immunodeficiency virus (HIV) type I protease (PR) and anti-lipid peroxidation effects on Rosa davurica were investigated. Of the various parts tested from R. davurica, the water extracts of stem and leaves inhibited the HIV-1 PR activity by more than 45% at a concentration of $100\;{mu}g/mL$. Hyperoside from the percarp of title plant showed 25% inhibition on HIV-1 PR at $200\;{mu}M$. The methanol extract of the root of R. davurica reduced the level of lipid peroxides induced by bromobenzene in vivo.

• 대한의생명과학회지
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• 제10권4호
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• pp.341-346
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• 2004

Tumor necrosis factor-α (TNF-α) or its mRNA expression are increased in acute nephrosis of various types including ischemia/reperfusion injury. This study was undertaken to determine whether pentoxifylline (PTX), an inhibitor of TNF-α production, provides a protective effect against hypoxia-induced cell injury in rabbit renal cortical slices. To induce hypoxia-induced cell injury, renal cortical slices were exposed to 100% N₂ atmosphere. Control slices were exposed to 100% O₂ atmosphere. The cell injury was estimated by measuring lactate dehydrogenase (LDH) release and p-aminohippurate (PAH) uptake. Exposure of slices to hypoxia increased the LDH release in a time-dependent manner. However, when slices were exposed to hypoxia in the presence of PTX, the LDH release was decreased. The protective effect of PTX was dose-dependent over the concentrations of 0.05∼1 mM. Hypoxia did not increase lipid peroxidation, whereas an organic hydroperoxide t-butylhydroperoxide (tBHP) resulted in a significant increase in lipid peroxidation. PTX did not affect tBHP-induced lipid peroxidation. Hypoxia decreased PAH uptake, which was significantly attenuated by PTX and glycine. tBHP-induced inhibition of PAH uptake was not altered by PTX, although it was prevented by antioxidant deferoxarnine. The PAH uptake by slices in rabbits with ischemic acute renal failure was prevented by PTX pretreatment. These results suggest that PTX may exert a protective effect against hypoxia-induced cell injury and its effect may due to inhibition of the TNF-α production, but not by its antioxidant action.

• Biomolecules & Therapeutics
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• 제30권2호
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• pp.184-190
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• 2022

Targeting the cystine/glutamate exchange transporter, system x_c^-, is a promising anticancer strategy that induces ferroptosis, which is a distinct form of cell death mediated by iron-dependent lipid peroxidation. The concentration of ⳑ-cystine in culture medium is higher than the physiological level. This study was aimed to evaluate the effects of ⳑ-cystine concentration on the efficacy of ferroptosis inducers in hepatocellular carcinoma cells. This study showed that treatment with sulfasalazine or erastin, a system x_c^- inhibitor, decreased the viability of Huh6 and Huh7 cells in a dose-dependent manner, and the degree of growth inhibition was greater in medium containing a physiological ⳑ-cystine concentration of 83 µM than in commercial medium with a concentration of 200 µM ⳑ-cystine. However, RSL3, a glutathione peroxidase 4 inhibitor, decreased cell viability to a similar extent in media containing both ⳑ-cystine concentrations. Sulfasalazine and erastin significantly increased the percentages of propidium iodide-positive cells in media with 83 µM ⳑ-cystine, but not in media with 200 µM ⳑ-cystine. Sulfasalazine- or erastin-induced accumulation of lipid peroxidation as monitored by C11-BODIPY probe was higher in media with 83 µM ⳑ-cystine than in media with 200 µM ⳑ-cystine. In contrast, the changes in the percentages of propidium iodide-positive cells and lipid peroxidation by RSL3 were similar in both media. These results showed that sulfasalazine and erastin, but not RSL3, were efficacious under conditions of physiological ⳑ-cystine concentration, suggesting that medium conditions would be crucial for the design of a bioassay for system x_c^- inhibitors.

• Journal of Microbiology and Biotechnology
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• 제10권2호
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• pp.233-237
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• 2000

As part of a continuing investigation to identify free radical scavengers from the fruit bodies of basidiomycetes, we isolated two p-terphenyl compounds, designated as PAl and PA2l, from cethanolic extract of the fruit body of Pasillus panuoides. The methanolic extract was processed by ethyl acetate extraction and silica gel column chromatography to yield two active fraction. PAl was obtained from one of the fractions through Sephadex LH-20 and silica gel column chromatographies and reverse-phase HPLC. The other fraction was purified by Sephadex LH-20 and reverse-phase column chromatographies to produce PA2. The compounds PA1 and PA2 were identified as leucomentin-4 and leucomentin-2, respectively, on the basis of various spectroscopic analyses. These compounds exhibited strong inhibitory activities against lipid peroxidation in rat liver microsomes with IC_{50}$ values of 0.10 and $0.06{\;}\mu\textrm{g}ml$, respectively.

• 대한의생명과학회지
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• 제15권4호
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• pp.355-362
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• 2009

I evaluated the protective effect of N-methyl-D-aspartate (NMDA)/glycine receptor antagonist, 7-chlorokinurenic acid (CKA) on cultured mouse astrocytes damaged by ischemia-like condition (ILC). The protective effect of CKA was assessed by cell viability, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD)-like activity and lipid peroxidation. To examine the effect of CKA on the cell apoptosis, the expression and the activity of caspase 3 were assessed by Western blotting. CKA increased the cell viability decreased by ILC. CKA also decreased the LDH activity and antioxidative effects such as SOD-like activity and inhibitory activity of lipid peroxidation. In addition, CKA suppressed the expression of caspase 3 associated with apoptosis, and increased the cell viability by the decrease of caspase 3 activity as like the caspase 3 inhibitor, Av-DVED-MED. From these results, these results suggest that ILS induces cell cytotoxicity in cultured astrocytes and CKA, NMDA/glycine receptor antagonist, is effective on the prevention of the cytotoxicity due to ILS by the antioxidative effect and the inhibition of apoptosis.

• Archives of Pharmacal Research
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• 제16권1호
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• pp.13-17
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• 1993

Several naturally occurring furanocoumarins significantly inhibited microsomal lipid peroxidation not only mediated by endogeneous iron and NADPH but also initiated by $CCL_4$ metabolites, phellopterin, a potent inhibibitor of cytochrome p-450, exhibited an almost complete inhibition of $CCL_4$-induced hepatotoxicity as measured by sGPT activity 24 hr after $CCL_4$ intoxication, whereas other furanocoumarins such as imperation, byakangelicin and oxypeucedanin methanolate exerted no protective effect. When compared with other cytochrome P-450 inhibitors(SKF-52A, AIA) and silymarin given at the same dose level $(ED_{50})$, phellopterin still showed a significant inhibition of hepatotoxicity which was even stronger than that of AIA, known as a typical suicide inhibitor. Phellopterin was partially effective when given 30 min after $CCL_4$ treatment. Repeated administrations of phellopterin, however, resulted in a complete loss of the protection against $CCL_4$-induced hepatotoxicity.

• 대한약리학회지
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• 제27권2호
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• pp.155-166
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• 1991

Paraquat 독성작용에 있어서 mitochondria의 잠재적인 역할을 평가하기 위하여, 이 약물의 산소 radical 생성과 지질과산화 반응에 미치는 영향을 mouse간의 submitochondrial particle 과 microsome에서 비교하여 보았다. Submitochondrial particle 사용시 NADH를, microsome 사용시 NADPH를 전자공여체로 이용한 경우 paraquat는 두 분획에서 superoxide anion과 hydrogen peroxide의 생성을 증가시켰다. 동일한 조건하에서 paraquat는 hydroxyl radical의 생성을 시사하는 methional로 부터 ethylene의 생성을 증가시켰다. 그러나, paraquat에 의한 이들 각각의 효과는 microsome에서 보다 submitochondrial particle에서 약간 낮았다. 한편, 두 분획 모두에서 paraquat는 지질과산화 반응을 촉진시켰다. Submitochondrial particle과 microsome에서의 Paraquat에 의한 지질과산화반응은 i) 두 분회에서 지질과산화는 SOD에 의해서 부분적으로 억제됨을 보였고, DETAPAC(iron chelator)에 의해서는 완전히 억제되었고, catalase와 hydroxyl radical scavenger에 의해서는 억제되지 아니하였으며, ii) 반응내 $ADP-Fe^{3+}$ 첨가로 paraquat에 의한 지질과산화는 더욱 증가되었지만 methional로 부터 ethylene 생성은 감소하여 hydroxyl radical 생성과 지질과산화 사이에는 상관성이 없음으로 보아 같은 기전을 통해 촉진됨을 알 수 있었고 이러한 촉진작용은 perferryl ion을 통하여 일어나리라 추측되었다. Submitochondrial particle에서 paraquat에 의해 촉진된 산소라디칼 생성과 지질과산화 반응은 p-hydroxymercuribenzoate(NADH dehydrogenase 억제제)에 의하여 억제되었으나 다른 respiratory chain 차단제들에 의해서는 거의 영향을 받지 않음으로 보아 mitochondria에서의 paraquat의 redox-cycling은 CoQ 보다는 NADH dehyrogenase와 관련이 있음을 시사하였다. 이상의 결과로 보아 산소 radical의 생성과 지질과산화를 유도하는 paraquat의 redox-cycling은 microsome에서와 마찬가지로 mitochondria에서도 일어나며, 이결과 생체내에서의 paraquat의 독작용에 관여함을 짐작할 수 있다.