• 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.

• Animal cells and systems
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• v.10 no.4
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• pp.211-217
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• 2006

Heavy metals are well known as important environmental pollutants and also considered as endocrine disrupters. This study was performed to evaluate the direct effects of heavy metals such as cadmium (Cd), zinc (Zn), mercury (Hg), lead (Pb), cobalt (Co), and arsenic (As) on the various steroidogenic enzymes in frog ovarian follicles. Ovarian follicles from Rana catesbeiana were isolated and cultured for 18 hours in the presence of frog pituitary homogenate (FPH, 0.05 gland/ml) or various steroid precursors with or without heavy metals (0.01-100 ${\mu}M$), and steroid levels in the follicle or culture medium were measured by radioimmunoassay (RIA). Thus, the steroidogenic enzyme activities were indirectly evaluated by measuring the converted steroid levels from the added precursor steroid. Among heavy metals, Hg, Cd and Zn significantly inhibited FPH-induced pregnenolone ($P_5$) production by the follicles ($EC_{50},\;4.0{\mu}M,\;25.6{\mu}M\;and\;5.7{\mu}M$, respectively ), and also suppressed the conversion of testosterone (T) to estradiol $17{beta}\;(E_2)\;(EC_{50},\;4.2{\mu}M,\;7.5{\mu}M\;and\;80.0{\mu}M) while Pb, Co and As are not or less effective in the inhibition. Other enzymes such as $C_{17-20}$ lyase and $17{\beta}$-hydroxysteroid dehydrogenase ($17{\beta}$-HSD) were suppressed only in the high concentration of Hg, Cd and Zn. Taken together, these data demonstrate that cytochrome P450 side chain cleavage (P450scc) and aromatase are much more sensitive to heavy metals than other steroidogenic enzymes and Hg, Cd and Zn show stronger toxicity to follicles than other heavy metals examined.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.2
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• pp.37-49
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• 2008

In this study, we experimented the influence of three herbal medicines, which are Saussurea lappa Clarke, Poncirus trifoliata Rafin, Citrus aurantium Linne, which are called 'Yigiyak(理氣藥)' on drug metabolizing enzyme cytochrome P450 3A4 in Human Liver Microsome. Above all, the reason for this study is that herbal medicines can be assumed that herbs might have interactions with drugs, other herbs, alcohol and chemicals whether those are much better synergy effects than expected effects when the medicine was treated alone or not. As a result, we showed that all of five traditional herbal medicines had no CYP 3A4 inhibition effect on 10, 20, 30, 40, $50{\mu}g/m{\ell}$ doses in Human Liver Microsome even Saussurea lappa Clarke showed a little inhibition as about 93% and 79% inhibition rate of control. However, this result are mostly not enough to prove that SLC has a CYP 3A4 inhibition effect. Moreover, it is not that those rates showed that those herbal medicines have CYP 3A4 induction effect. In conclusion, the result could support that those herbal medicines are more safe than chemical drugs even if this is the basic step to prove that result. Therefore, more specific studies to support this result, which are Kinetic study, cell and animal study then finally until clinical research, are required.

• BMB Reports
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• v.46 no.3
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• pp.151-156
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• 2013

Phylogenetic and amino acid sequence analysis indicated that rice allene oxide synthase-1 (OsAOS1) is CYP74, and is clearly distinct from CYP74B, C and D subfamilies. Regio- and stereo-chemical analysis revealed the dual substrate specificity of OsAOS1 for (cis,trans)-configurational isomers of 13(S)- and 9(S)-hydroperoxyoctadecadienoic acid. GC-MS analysis showed that OsAOS1 converts 13(S)- and 9(S)-hydroperoxyoctadecadi(tri)enoic acid into their corresponding allene oxide. UV-Visible spectral analysis of native OsAOS1 revealed a Soret maximum at 393 nm, which shifted to 424 nm with several clean isobestic points upon binding of OsAOS1 to imidazole. The spectral shift induced by imidazole correlated with inhibition of OsAOS1 activity, implying that imidazole may coordinate to ferric heme iron, triggering a heme-iron transition from high spin state to low spin state. The implications and significance of a putative type II ligand-induced spin state transition in OsAOS1 are discussed.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.243-248
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• 2009

The purpose of this study was to investigate the effects of morin, an antioxidant, on the bioavailability of doxorubicin (DOX) in rats. Thus, DOX was administered intravenously (10 mg/kg) or orally (50 mg/kg) with or without oral morin (0.5, 3 and 10 mg/kg). In the presence of morin, the total area under the plasma concentration-time curve (AUC) of DOX was significantly greater than that of the control. In the presence of 3 and 10 mg/kg of morin, the peak concentration $C_{MAX}$) was significantly higher than that of the control. Consequently, the absolute bioavailability (AB) of DOX in the presence of morin was 3.7-8.3%, which was significantly enhanced compared with those of the control group (2.7%). The relative bioavailability (RB) of DOX was 1.36 to 3.02 times higher than those of the control group. Compared to the intravenous control, the presence of morin increased the AUC of DOX, but was not significantly affected. The enhanced bioavailability of oral DOX by oral morin may be due to the inhibition of both P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A in the intestine and/or liver by morin. This result may suggest that the development of oral DOX combination with morin is feasible, which is more convenient than the i.v. dosage forms. The present study raised the awareness about the potential drug interactions by concomitant use of DOX with morin.

• Journal of Microbiology and Biotechnology
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• v.15 no.1
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• pp.188-191
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• 2005

Abstract Cyclosporins are a family of clinically-important immunosuppressive cyclic peptides produced by Tolypocladium inflatum. The structural modification of cyclosporins via hydroxylation at various positions of N-methyl leucines in cyclosporin A leads to a dramatic change of their bioactive spectra. Among over 100 soil actinomycetes screened, two actinomycetes species, Sebekia benihana and Pseudonocardia autotrophica, were identified to contain superior cyclosporin A hydroxylation activities. A HPLC-based cyclosporin A hydroxylation assay revealed that each strain possesses distinctive hydroxylation specificity and regiospecificity; mono-hydroxylation at the 4th N-methyl leucine of cyclosporin A by S. benihana, and di-hydroxylations at both 4th and 9th N-methyl leucines of cyclosporin A by P. autotrophica. The conversion yields for cyclosporin A hydroxylation by both S. benihana and P. autotrophica were significantly improved from less than 10% and 18% up to 58% and 45%, respectively, in the optimized culture containing molybdenum with 0.05 g/l of cyclosporin A concentration. An ancymidol-specific inhibition of cyclosporin hydroxylation also suggested that the regiospecific cyclosporin hydroxylation might be catalyzed by a putative cytochrome P450 mono-oxygenase enzyme.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.88.1-88.1
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• 2003

CJ-11668 is a new potent and selective COX-2 inhibitor (IC$\sub$50/ COX-2 65nM; COX-l/COX-2 ratio 770). The pharmacokinetic profile of CJ-11668 (20 mg/kg, p.o.) in the rat was characterized by high bioavailability (90%) and long plasma half-life (11.7 hr) with low clearance (0.4 L/hr/kg). In the dog, the PK profiles (2 mg/kg, p.o.) also showed long plasma half-life (l7.9hr) with low clearance (0.5 L/hr/kg), and the bioavalability of 60%. The inhibition of CJ-11668 infive different cytochrome P450 isozymes (1A2, 2C9, 2C19, 2D6 and 3A4) was determined in vitro and had observed no significant effect. (omitted)

• Biomedical Science Letters
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• v.9 no.2
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• pp.93-98
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• 2003

To investigate the cyclohexane and xylene mixture treatment on the liver damage, the rats were treated by the mixture of cyclohexane and xylene (CH＋X) and then, liver damage was demonstrated by liver function findings based on liver weight/body weight, serum level of alanine aminotransferase (ALT), xanthine oxidase (XO) and then compared with cyclohexane treated group (CH group) and xylene-treated group (X). The CH＋X group showed merely severer liver damge than CH or X group. On the other hand, CH＋X group showed lower activity of hepatic cytochrome P-450 dependent aniline hydroxylase (CYPdAH) than CH or X group, but no statical differences were demonstrated among three experimental groups. Especially the hepatic GSH content was merely declined than CH or X group and the activity of hepatic GST was higher in CH＋X group than CH or X group. In conclusion, cyclohexane and xylene mixture treated animals showed merely severer liver damage than cyclohexane or xylene treated group and such a fact may be caused by inhibition of cyclohexane or xylene metabolism and oxygen free radical.

• YAKHAK HOEJI
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• v.22 no.4
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• pp.175-192
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• 1978

Chlorination of the polluted water may produce odoriferous and objectionable-tasting chlorophenols which are hazardous to health. These studies were undertaken to investigate the hazardous effects of chlorophenols to the rat. 1. The chlorophenols such as o-chlorophenol and 2,6-dichlorophenol inhibited rat growth and caused increment of the ratio between liver weight and body weight. 2. The hemoglobin content, hamatocrit ratio and A/G of rat blood were decreased by chlorophenols administration. The activities of alkaline phosphatase, lactic dehydrogenase (LDH) and glutamate oxaloacetate transaminase (GOT) in serum as well as in liver were increased provisonally and decreased after one or two weeks adminstration. 3. The liver mitochondrial respiration ($QO_{2}$) was inhibited by chlorophenols treatment in in-vivo and in-vitro test. 4. The liver microsomal cytochrome P-450 was decreased by chlorophenols administration 5. Liver tissue was degenerated with congestion, atrophy, swelling, vacuolation, dilation of rough endoplasmic reticulum and denature of mitochondrial particle with swelling, and cristal destruction by chlorophenols adminstration. 6. After one and two weeks of adminstration of chlorophenols to rat, the aberrations of bone marrow chromosome and inhibition of its mitosis were observed respectively.

• Toxicological Research
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• v.14 no.3
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• pp.321-328
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• 1998

This study was performed to evaluate the effect of liver damage on toluene metabolism in rats pretreated with carbon tetachloride. Liver damage in rats was induced by administration of 0.1ml of carbon tetrachloride per 100g of body wight intraperitoneally every day for four weeks except the last day before sacrifice. One day before sacrifice, toluene was administered to the animals instead of carbon tetrachloride. Rats were sacrificed at the 1st, the 2nd, the 3rd and the 4th week after the first administration of carbon tetachloride. Based on the histopathological findings, liver weight and serum alanine aminotransferase, the $CCl_4$-preteated group was found to have gradual severe liver damage. Especially the degree of liver injury became increasingly severe throughout the whole course of the experiment. The contnts of hippuric acid in urine lower in the all groups pretreated with $CCl_4$than that of the control. The contents of hepatic cytochrome P450(CYP), benzylalcohol dehydrogenase and benzaldehyde dehydrogenase activities were decreased in $CCl_4$-pretreated rats than those of the control. The $CCl_4$treated animals showed the gradual decreased activities of these enzyme as injection times elapsed. Km values of the benzylalcohol dehydrogenase in pooled liver samples from $CCl_4$-pretreated or control groups were similar. On the other hand, Vmax values of the $CCl_4$-pretreated group was lower than of the control. Therefore, it can be concluded that reduction of the toluene metabolism in damaged rat liver induced with $CCl_4$was due to the inhibition of CYP content, bezylalcohol and benzaldehyde dehydrogenase activities which related with toluene metabolic enzyme system.