• Environmental Analysis Health and Toxicology
• /
• 제19권3호
• /
• pp.251-259
• /
• 2004

Xenoestrogens are chemicals with diverse structure that mimic estrogen. Bisphenol A, a monomer of polycarbonate and epoxy resins, has been detected in canned food and human saliva. Bisphenol A stimulate cell proliferation and induce expression of estrogen -response genes in vitro. The purpose of the this study was to evaluate cell proliferation of bisphenol A in the presence of a rat liver 59 mix contaning cytochrome P450 enzymes and Cu (II). The fragmentation of intact DNA, a parameter of apoptotic cell death, was evaluated quantitatively by diphenylamine reaction method. Bisphenol A induced apoptotic cell death in a dose-dependent manner The effect of radical scavenger on the apoptotic cell death induced bisphenol A was investigated. The DNA fragmentation induced by bisphenol A was significantly inhibited by addition of radical scavenger to the culture medium. This indicated that elevated oxidative stress caused by imbalance between the production and removal of free radicals occurred in cells. Taken together, these results suggest that free radical reacts with Cu (II) leading oxidative stress.

• Toxicological Research
• /
• 제31권1호
• /
• pp.25-32
• /
• 2015

The objectives of this study were to investigate the individual characteristics, lifestyle habits, exposure levels, and genetic diversity of xenobiotic-metabolizing enzymes involved in toluene metabolism in Korean and foreign workers exposed to toluene at a manufacturing plant. This study was conducted to determine the effects of culture or ethnicity on toluene metabolism. The results showed that blood and urinary toluene concentrations were dependent on the level of exposure to toluene. We analyzed the correlation between toluene metabolism and genetic diversity in glutathione S-transferase (GST) (M1), GSTT1, and cytochrome p-450 (CYP) $2E1^*5$ as well as lifestyle habits (smoking, drinking, and exercise habits). The results revealed significant correlations between toluene metabolism and GSTM1 and GSTT1 genetic diversity, as well as smoking and exercise.

• Environmental Analysis Health and Toxicology
• /
• 제18권3호
• /
• pp.175-182
• /
• 2003

Bisphenol A shares similarities in structure, metabolism and action with DES, a known human teratogen and carcinogen. Bisphenol A, a monomer of polycarbonate and epoxy resins, has been detected in canned food and human saliva. The purpose of the this study was to evaluate the cytotoxicity, cell proliferation of bisphenol A In the presence of a rat liver S9 mix, contaning cytochrome P450 enzymes, and Cu (II). In the present study, Bisphenol A in combination with Cu (II) exhibited a enhancement in cytotoxicity which were inhibited by free radical scavengers. The content of malondialdehyde, an end product of lipid peroxidation, was also found to increase with concentration of bisphenol A. Also, we examined the change of CuZn-SOD, Mn-SOD, catalase and GPx activities in the MCF-7 cells exposed to bisphenol A. The activities of CuZn-SOD, CPx, catalase were found to decrease with bisphenol A concentration. Meanwhile, the activity of Mn-SOD was unchanged. This indicated that elevated oxidative stress caused by imbalance between the production and removal of free radicals occurred in cells.

• Preventive Nutrition and Food Science
• /
• 제3권1호
• /
• pp.67-70
• /
• 1998

To investigate an effect of Gam-Roa tea on the free radical or alcohol detoxicating enzyme activities, the rats got a drink at the Gam-Roa tea instead of water for 3 months, and then the animals were sacrificed and obtained the following findings. The animals receiving Gam-Roa tea showed a decreasing tendency of hepatic xanthine oxithine oxidase activity and significantly incresed content of cytochrome P-450 compared with the control. Furthermore, hepatic superoxide dismutase and glutathione S-transferase activities were also more increased in rats received Gam-Roa tea than in the control group, those receiving water. On the other hand, alcohol or aldehyde dehydrogenase activities were more increased in rats receiving Gam-Roa tea than the control. In conclusion, it is likely that the liver of rats receiving Gam-Roa tea may have the oxygen free radical or alcohol detoxication potential.

• 한국환경성돌연변이발암원학회:학술대회논문집
• /
• 한국환경성돌연변이발암원학회 2004년도 춘계학술대회
• /
• pp.57-57
• /
• 2004

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.286.2-287
• /
• 2003

The purpose of this paper was to identify the metabolic pathway of a new neuroprotective agent, KR-31543 for ischemia-reperfusion damage in human liver microsomes and characterize cytochrome P450 (CYP) enzymes involved in the in vitro metabolism of KR-31543 generates two metabolites in human liver microsomes : M1, N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine and M2, hydroxy-KR-31543. (omitted)

• Toxicological Research
• /
• 제3권1호
• /
• pp.1-8
• /
• 1987

In vitro induction of cytochrome 450 associated monooxygenase activities by phenobarbital (PB) and 3-methylcholanthrene (MC) was investigated in primary cultures of adult rat hepatocytes. PB and MC were added to the culture 24 hr after the initial plating of hepatocytes. A signiftcant increase of the activities of 7-ethoxycoumarin 0-deethylase and aryl hydrocarbon hydroxylase were observed in MC and PB treated culture. MC caused about 500% induction of the initial oxidation rates of both enzymes in 48 hr. However the PB maintained both enzyme activities close to the level of freshly isolated hepatocytes. Biphenyl 4-hydroxylase and aminopyrine N-demethylase activities were also induced by MC and PB. But the level of induction was less than that occuring with 7-ethoxycoumarin 0-deethylase and aryl hydrocarbon hydroxylase. When aflatoxin $B_1$ was added to the hepatocyte cultures which have been treated with MC or PB, it caused a significant increase of the unscheduled DNA synthesis at higher dose of aflatoxin $B_1$ as compared to those of untreated control hepatocyte cultures. The results suggest that microsomal enzyme activities can be selectively controlled preferably in hepatocyte cultures by the in vitro induction method. This principle may be useful for studying the metabolism and other toxicological studies.

• 한국식품영양과학회지
• /
• 제28권6호
• /
• pp.1364-1368
• /
• 1999

This study was carried out to investigate the inhibiton effects of Coprinus comatus ethanol extract of edible mushroom on liver damage in benzo(a)pyrene (B(a)P) treated mice. The activities of serum aminotransferase, cytochrome P 450 and hepatic content of lipid peroxide after B(a)P treatment were increased than those of control, but those levels were significantly decreased by the treatment of Coprinus comatus ethanol extract. Whereas, the hepatic glutathione content and glutathione S transferase activity were decreased by B(a)P treatment than those of control, but those were increased by the treatment of Coprinus comatus ethanol extract. Also the activities of superoxide dismutase, catalase and glutathione peroxidase after B(a)P treatment were markedly increased than those of control, but those levels were decreased by the treatment of Coprinus comatus ethanol extract. These results suggest that Coprinus comatus ethanol extract have a protective effect on liver damage by benzo(a)pyrene through the mechanisms of decreasing lipid peroxide and activities of free radical generating enzymes.

• Biomolecules & Therapeutics
• /
• 제19권2호
• /
• pp.237-242
• /
• 2011

This study was designed to investigate the effects of glipizide on the pharmacokinetics of carvedilol after oral or intravenous administration of carvedilol in rats. Clinically carvedilol and glipizide can be prescribed for treatment of cardiovascular diseases as the complications of diabetes, and then, Carvedilol and glipizide are all substrates of CYP2C9 enzymes. Carvedilol was administered orally or intravenously without or with oral administration of glipizide to rats. The effects of glipizide on cytochrome P450(CYP) 2C9 activity and P-gp activity were also evaluated. Glipizide inhibited CYP2C9 activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of 18 ${\mu}M$. Compared with the control group, the area under the plasma concentration-time curve (AUC) was significantly increased by 33.0%, and the peak concentration ($C_{max}$) was significantly increased by 50.0% in the presence of glipizide after oral administration of carvedilol. Consequently, the relative bioavailability (R.B.) of carvedilol was increased by 1.13- to 1.33-fold and the absolute bioavailability (A.B.) of carvedilol in the presence of glipizide was increased by 36.8%. After intravenous administration, compared to the control, glipizide could not significantly change the pharmacokinetic parameters of carvedilol. Therefore, the enhanced oral bioavailability of carvedilol may mainly result from inhibition of CYP2C9-mediated metabolism rather than both P-gp-mediated effl ux in the intestinal or in the liver and renal elimination of carvedilol by glipizide.

• 대한한의학회지
• /
• 제38권2호
• /
• pp.15-30
• /
• 2017

Objectives: Hwangryunhaedok-tang (HHT; Huanglianjiedu-tang, Orengedoku-to), a traditional herbal formula, is used for treating inflammation, hypertension, gastritis, liver dysfunction, cerebrovascular diseases, dermatitis and dementia. The objective of this study was to assess the sub-acute toxicity of HHT in Sprague-Dawley (SD) rats, and its effect on the activities of human microsomal cytochrome P450s (CYP450s) and UDP-glucuronosyltransferases (UGTs). Methods: Male and female SD rats were orally administered HHT once daily at doses of 0, 500, 1000 and 2000 mg/kg for 4 weeks. We analyzed mortality, clinical observations, body weight, food consumption, organ weights, urinalysis, hematology, serum biochemistry, and histopathology. The activities of major human CYP450s (CYP1A2, CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP2E1) and UGTs (UGT1A1, UGT1A4, and UGT2B7) were assessed using in vitro fluorescence- and luminescence-based enzyme assays, respectively. Results: No toxicologically significant changes related to the repeated administration of HHT were observed in both male and female SD rats. The no observed adverse effect level (NOAEL) value was more than 2000 mg/kg/day for both sexes. HHT inhibited the activities of human microsomal CYP1A2, CYP2C19, CYP2D6, and CYP2E1, whereas it weakly inhibited the activities of CYP2B6, CYP2C9, CYP3A4, and UGT1A1. In addition, HHT negligibly inhibited the activities of human microsomal UGT1A4 and UGT2B7 with $IC_{50}$ values in excess of $1000{\mu}g/mL$. Conclusions: Our findings indicate that HHT may be safe for repeated administration up to 4 weeks. In addition, these findings provide information on the safety and effectiveness of HHT when co-administered with conventional drugs.