• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.43-48
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• 2004

• Proceedings of the Korean Society of Toxicology Conference
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• 2004.05a
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• pp.43-48
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• 2004

• Journal of Life Science
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• v.12 no.2
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• pp.136-143
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• 2002

Jaboyangyeong-hwan (IAE) has been known as a traditional medicine for the treatment of debility, fatigue, and liver diseases. The hepatoprotective effect of the water extract of Jaboyangyeong-hwan was investigated against carbon tetrachloride ($CCl_4$)-induced hepatic damage. A single intraperitoneal injection of $CCl_4$produced liver damage in rats as manifested by the significant rise of aspartate aminotransferase (AST, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in serum as compared to those of untreated normal group. Pretreatments of rats with the JAE extract (300, 600, and 1200 mg/kg for 7 days) were significantly reduced AST, ALT, and ALP levels compared with $CCl_4$-treated control group. Treatment of rats with $CCl_4$led to significantly increase in lipid peroxidation and significantly decrease in cytochrome P450 and P450 reductase. The oral administration of the JAE extract significantly inhibited the accumulation of microsomal thiobarbituric acid reactive substance (TBARS) and increased the cytochrome P450 and P450 reductase activity. All these biochemical alterations resulting from $CCl_4$administration were inhibited by the pretreatment with JAE extract. These results suggest that JAE water extract can be useful as a hepatoprotective agent.

• Journal of Preventive Medicine and Public Health
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• v.32 no.1
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• pp.88-94
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• 1999

Objectives. In order to gain a better understanding of the mechanism of DMF toxicity, recent studies have focused on hepatic drug metabolizing enzymes. In this study, we investigated the effects of DMF on the induction of P450 and the activities of other related enzymes in rat liver microsomes. Methods. DMF was administered to male Sprague Daweley rats by intraperitoneal injection at 0(control), 450(D1), 900(D2), 1,800(D3) mg DMF/kg body weight in olive oil once a day for three days. Hepatic P450 was measured by method of Omura and Sato. We evaluated selective assays for the three drug metabolizing cytochrome P450 isoenzymes 1A1, 2B1 and 2E1. Results. The content of microsomal protein, P450 and b5 were tended to be decreased in DMF treated group, but they were not statistically significant. The activity of NADPH-cytochrome P450 reductase was significantly increased dose dependently(p<0.01), but the activity of NADH-b5 reductase was decreased in the treated group(p<0.01). The activities of PROD and EROD were not significant between control and treated group. The activities of pNPH in the DMF treated groups were higher than that of the control group(p<0.01). When Western immunoblottings were carried out utilizing three monoclonal antibodies which were specific against P4501A1/1, P4502B1/2 and P4502E1, the strong density band corresponding to P4502E1 was observed with the microsomes obtained from the rats treated with DMF. But there were no significant increased in the P4501A1/2 and P4502B1/2 band densities in immunoblotting. Conclusions. These result suggested that P4502E1 was inducible by DMF and P4502E1 isozyme might be responsible for the hydroxylation of DMF to HMMF.

• 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.

• Korean Journal of Environmental Biology
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• v.21 no.1
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• pp.18-25
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• 2003

Effects of tributyltin chloride (TBTC) in vitro on mixed function oxygenase (MFO) system on liver microsome of eight marine fish species were investigated. To determine the effects on MFO system, cytochrome P45O (CYP) and cytochrome b5 con-tents, activities of two reductases (NADH-cytochrome b5 reductase and NADPH-cy-tochrome P450 reductase) and four dealkylation enzymes (EROD, PROD, MROD and ECOD) were measured in fish microsoms exposed to TBTC for 20 min. The WP content was reduced to 10% of the control group in 6 out of 8 species exposed to TBTC, whereas there was no significant change in the cytochrome bs content. the response of NAD(P)H dependant reductases depended on fish species. The dealkylation enzyme activities in microsome were also apparently inhibited by TBTC. The degree of inhibition was different among fish species and four enzymes. The EROD activities in eight species were decreased to the range of 1∼65% of control group.

• Korean Journal of Environmental Biology
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• v.26 no.2
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• pp.102-108
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• 2008

Many alternative biocidal additives were applied to antifouling paint to replace TBT, and Sea-Nine 211 is one of alternating organic booster compounds used in antifouling paint. In this study, extent of Sea-Nine 211 toxicity on marine benthic bivalve is evaluated. Sea-Nine 211 was injected to surf clam, Pseudocardium sachalinensis, that inhabitate northern part of Gangwon Province, Korea. Survival rate of the clam and xenobiotics metabolizing enzyme activities in digestive gland were measured during 4 day-exposure period. The results were compared with those of TBT exposed clam. There were no mortality of clam in the solvent (DMSO) control group and the three Sea-Nine 211 exposure groups (5, 25, 50 mg kg$^{-1}$ body weight), while the clam exposed to 1, 2 and 5 mg kg$^{-1}$ TBT chloride (TBTC) demonstrated 70, 30 and 0% survival rate, respectively. The Sea-Nine 211 exposure group showed a tendency of cytochrome P450 (CYP) induction according to the exposure duration, on the other hand, CYP content was decreased in the TBT exposure group. NADPH cytochrome P450 reductase activity slightly increase according to the exposure duration in the Sea-Nine 211 exposure group, while TBTC inhibit its activity as CYP content. Moreover, there was no significant change of NADH cytochrome b5 reductate activity in the clam epxosed to Sea-Nine 211. In the TBTC exposure group, its activity increased in early exposure period and then significantly decreased the rest of exposure period. All the results indicate that Sea-Nine 211 demonstrated a tendency to induce CYP level, while TBTC inhibits the CYP level, NADPH cytochrome P450 reductase and NADH cytochrome b5 reductase activities.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.143-143
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• 2001

Human cytochrome P450 (CYP or P450) 3A4 (CYP3A4) is the most abundant among P450s in human liver. We previously reported that the expression of CYP3A4 in membranes prepared from E. coli coexpressed the bicistronic construct of CYP3A4 and NADPH-P450 reductase with cytochrome b$_{*}$ (b5) was showed 20-60% higher than that in membranes from E. coli expressed only the bicistronic construct with culturing longer times (48-72h).(omitted)

• Korean Journal of Pharmacognosy
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• v.34 no.4 s.135
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• pp.297-302
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• 2003

Cnidii Rhizoma water extract (CRW) was tested for liver cancer chemopreventive potential by measuring the inhibition of phase I enzyme and benzo[a]pyrene-DNA adduct formation and induction of phase II detoxification enzymes. There was 17.0% inhibition in the activity of cytochrome P450 1A1 enzyme with the treatment of 150 mg/ml CRW. At concentration of 30 mg/ml CRW, the binding of $[^3H]B[a]P$ metablites to DNA of NCTC-clone 1469 cell was inhibited by 33.3%. CRW was potent inducer of quinone reductase (QR) and glutathione S-transferase (GST) activities in cultured murine hepatoma Hepalc1c7 cells. However, hepatic glutathione (GSH) level was not influenced by CRW. These findings suggest that CRW has chemopreventive potential of liver cancer by inhibiting cytochrome P450 1A1 activity and benzo[a]pyrene-DNA adduct formation and inducing QR and GST activities.

• YAKHAK HOEJI
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• v.23 no.2
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• pp.111-118
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• 1979

It was previously reported that cytochrome P$_{450}$ content in liver was increased when Capsicum acetone extract was given chronically to rats. The present study is aimed to investigate the effect of capsaicin, a principal component of red pepper, on the drug metabolizing enzymes in rat liver. Capsaicin (5mg/kg) was given intraperitoneally once a day for seven days and zoxazolamine paralysis time and hexobarbital sleeping time were determined 24 hrs after the last dose of capsaicin. Plasma hexobarbital concentration was also determined five and 15 min after hexobarbital administration to rats. Zoxazolamine paralysis time and hexobarbital sleeping time were shortened by 31.6% and 37.1%, respectively, compared with control group. Plasma hexobarbital concentration was lowered by 26.2% after five min and by 35.2% after 15 min, respectively, compared with control group. However, administration of single dose of capsaicin did not affect the zoxazolamine paralysis time and hexobarbital sleeping time. Microsomal cytochrome P$_{450}$ content and NADPH-cytochrome C reductase activity were increased by 14.6% and 11.6%, respectively in the rats pretreated with capsaicin for seven days, while cytochrome b$_{5}$ content was not changed. These results suggest that treatment with capsaicin for seven days may induce the drug metabolizing enzyme in rat liver.