• Fisheries and Aquatic Sciences
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• v.5 no.1
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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.

• Microbiology and Biotechnology Letters
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• v.24 no.5
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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.

• Microbiology and Biotechnology Letters
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• v.26 no.6
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• pp.558-561
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• 1998

In the screening for lipid peroxidation inhibitors from edible mushroom, Agrocybe cylindracea, a bioactive compound AG 8 was isolated. The AG 8 was purified from methanol extract of its fruit body by Diaion HP-20 column chromatography, ethyl acetate extraction, and silica gel column chromatography, consecutively. Based on various NMR studies including $^1$H irradiation and HMBC experiments, the AG 8 was identified as MTA, 5'-deoxy-5'-methylthioadenosine. This compound inhibited lipid peroxidation with an $IC_{50}$/ value of 3.2 $\mu\textrm{g}$/$m\ell$. The MTA was isolated for the first time from basidiomycetes.

• Korean Journal of Pharmacognosy
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• v.31 no.3
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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.

• Biomedical Science Letters
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• v.10 no.4
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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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• v.30 no.2
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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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• v.10 no.2
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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.

• Biomedical Science Letters
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• v.15 no.4
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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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• v.16 no.1
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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.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.155-166
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• 1991

In order to evaluate a potential role of mitochondria in the mediation of toxicity of paraquat (PQ), submitochondrial particle and microsome of mouse liver were compared by oxygen radical generation and lipid peroxidation. With NADH in submitochondrial particle and NADPH in microsome as electron donors, PQ stimulated production of superoxide anion and $H_2O_2$ in both fractions. Under the same conditions, PQ enhanced the generation of ethylene from methional suggestiong stimulation of OH production by PQ. But these effects by PQ were somewhat lower in submitochondrial particle than in microsome. In addition, lipid peroxidation(measured as MDA production) was stimulated by PQ in both fractions. The stimulation of lipid peroxidation in both fractions seemed to occur by the same mechanism probably through perferryl ion. This was supported by the following findings: i) The lipid peroxidation in both fractions was partially inhibited by SOD and completely inhibited by DETAPAC(an iron chelator) but not by catalase or OH scavenger. ii) Addition of $ADP-Fe^{3+}$ further increased PQ-induced lipid peroxidation but decreased ethylene production from methional suggesting no correlation between OH production and lipid peroxidation. The redox-cycling of PQ in mitochondria appeared to be linked to NADH dehydrogenase, not to CoQ since all of the observed stimulations by PQ in submitochondrial particle were inhibited by p-hydroxymercuribenzoate(a NADH dehydrogenase inhibitor) but not affected by other respiratory chain blockers. The above results demonstrate that redox-cycling properties of PQ leading to oxygen radical generation and lipid peroxidation can also occur in mitochondria in the same manner as in microsome. Therefore, the observed actions of PQ in mitochondria suggest that mitochondria may also contribute to toxicity of this drug in vivo.