• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.579-585
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• 2003

The studies were carried out on the correlation between microsomal lipid peroxidation level and drug metabolizing enzyme activities in rat liver microsomal suspensions on various ages (2-week-old, 2, 4, 8, and 12-month-old). The lipid peroxidation levels of liver homogenates tended to be elevated in a 4-month-old rat livers, but it was a little decreased in 8 and 12-month-old rat livers. The lipid peroxidation levels of microsomal suspension was not shown any significant differences by ages. Lipid peroxidation levels and microsomal cytochrome P450 and NADPH-cytochrome c reductase activity showed a direct correlation (r=0.72 and r=0.64), respectively. The activities of cytochrome P450-dependent aminopyrine-N-demethylase and benzpyrene hydroxylase in rat liver microsomes were increased by ages up to 8-month-old rats and maintained in 12-month-old rats. The correlation between lipid peroxidation levels and these cytochrome-dependent enzyme activities showed a high direct correlation (r=0.97 and r=0.81), respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1757-1760
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• 2012

Breast cancer is a major cause of death in women worldwide. Mammary tissue expressing xenobiotic metabolizing enzymes metabolically activate or detoxify potential genotoxic breast carcinogens. Deregulation of these xenobiotic metabolizing enzymes is considered to be a major contributory factor to breast cancer. The present study is focused on the expression of the xenobiotic metabolizing gene, CYP1A1, in breast cancer and its possible relationships with different risk factors. Twenty five tumors and twenty five control breast tissue samples were collected from patients undergoing planned surgery or biopsy from different hospitals. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and western-blotting were used to investigate the expression of CYP1A1 in breast cancer control and disease samples. mRNA expression of CYP1A1 was down-regulated in 40% of breast tumor samples. Down-regulation was also observed at the protein level. Significnat relations were noted with marital status and tumour grade but not histopathological type. In conclusion, CYP1A1 protein expression was markedly reduced in tumor breast tissues samples as compared to paired control tissue samples.

• Korean Journal of Pharmacognosy
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• v.24 no.1
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• pp.69-77
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• 1993

Saikosaponins, originally isolated from Bupleuri Radix, were reported to exhibit diverse biological activities especially concerning with liver function. To elucidate the mode of protective action of saikosaponins on liver injury due to the acetaminophen administration, effects on drug metabolizing enzymes system and some transferase activities were checked. As the result, activities of transferase were shown to be strengthened by saikosaponin treatments significantly.

• YAKHAK HOEJI
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• v.30 no.2
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• pp.62-67
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• 1986

It was attempted to observe the effect of garlic on the hepatic purine metabolizing enzymes in this study. The activities of adenosine deaminase, guanase, and uricase in rats were not changed significantly following the feeding of 5% garlic juice. Whereas, garlic juice inhibited significantly the hepatic xanthine oxidase activity compared to control group with the lapse of treated-period. The orate level of serum in rats was significantly decreased by the treatment of garlic juice. The above inhibitory effect of garlic was greater in boiled garlic juice than fresh garlic juice-treated group. These results indicated that, according to the chemical properties of allicin which is unstable in heat, other components than allicin in garlic may regulate the hepatic purine metabolizing enzymes.

• Archives of Pharmacal Research
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• v.13 no.3
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• pp.265-268
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• 1990

The effects of lignans, related to macelignan, on hepatic microsomal drug-metabolizing enzyme (DME) activity were evaluated to elucidate the structure-activity relationship in mice and rats. The compounds carrying the methylenedioxyphenyl nucleus were found to be the msot potent among compounds tested; which not only produced a marked inhibition of DME with a single dose but a significant induction with repeated treatments. Lack of the methylenedioxy group caused marked decrease in the activity, implying that a methylenedioxy group is essential and of major importance eliciting DME modifying activity.

• Environmental Mutagens and Carcinogens
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• v.23 no.1
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• pp.23-29
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• 2003

To determine the frequencies of the genotypes of estrogen metabolising enzyme (CYP17, CYP1A1, CYP1B1, and COMT) and to identify the high-risk genotypes of these metabolic enzymes to breast cancer in Korean, the author has analysed 115 breast cancer patients and corresponding age and sex matched heathy controls using polymerase chain reaction-restiction fragment length polymorphism (PCR-RFLP). A2/A2 genotype in CYP17 polymorphism, m2/m2 genotype in CYP1A1 polymorphism, and Val/Val genotype in CYP1B1 had 0.95, 1.40 and 0.76 relive risks to breast cancer comparing with reference genotypes of each polymorphism, respectively. Among the genotypes of COMT enzyme polymorphism, L/H and L/L genotypes had 0.97 and 1.54 relative risks to breast cancer, respectively. According to the number of high risk genotype, the patients with one or two putative high risk genotypes had 0.95 and 1.94 relative risks to breast cancer, respectively. This study have demonstrated the unique frequency of genotypes of estrogen metabolizing enzyme in Korean healthy women, which will provide the basic data and insights to study the estrogen related conditions in Korean women including breast and endometrial cancers. And it also indicates that the well-known high risk genotypes of estrogen metabolizing enzymes are not significantly associated with the development of breast cancer in Korean women.

• Fisheries and Aquatic Sciences
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• v.15 no.1
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• pp.21-27
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• 2012

Ground seawater in the east area of the volcanic Jeju Island contains abundant minerals. We investigated the metabolic activity of electrodialyzed, desalted ground seawater (EDSW) from Jeju in both cultured cells and animals. The addition of EDSW to the culture medium (up to 20%, v/v) reduced the leakage of lactate dehydrogenase and increased MTT activity in CHO-IR cells. EDSW (10%) promoted insulin-induced glucose consumption in L6 muscle cells as well as the activities of the liver ethanol-metabolizing enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. Moreover, EDSW suppressed palmitate-induced intracellular fat accumulation in human hepatoma $HepG_2$ cells. Activities of AMP-stimulated protein kinase and acetyl CoA carboxylase, enzymes that modulate fat metabolism, were altered by EDSW in $HepG_2$ cells toward the suppression of intracellular lipid accumulation. EDSW also suppressed hepatic fat accumulation induced by a high-fat diet in mice. Taken together, EDSW showed beneficial metabolic effects, including the enhancement of ethanol metabolism and insulin-induced glucose consumption, and the suppression of intrahepatic fat accumulation.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.253-265
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• 2024

Orally administered ginsenosides, the major active components of ginseng, have been shown to be biotransformed into a number of metabolites by gastric juice, digestive and bacterial enzymes in the gastrointestinal tract and also in the liver. Attention is brought to pharmacokinetic studies of ginseng that need further clarification to better understand the safety and possible active mechanism for clinical application. Experimental results demonstrated that ginsenoside metabolites play an important role in the pharmacokinetic properties such as drug metabolizing enzymes and drug transporters, thereby can be applied as a metabolic modulator. Very few are known on the possibility of the consistency of detected ginsenosides with real active metabolites if taken the recommended dose of ginseng, but they have been found to act on the pharmacokinetic key factors in any clinical trial, affecting oral bioavailability. Since ginseng is increasingly being taken in a manner more often associated with prescription medicines, ginseng and drug interactions have been also reviewed. Considering the extensive oral administration of ginseng, the aim of this review is to provide a comprehensive overview and perspectives of recent studies on the pharmacokinetic properties of ginsenosides such as deglycosylation, absorption, metabolizing enzymes and transporters, together with ginsenoside and drug interactions.

• The Journal of Korean Medicine
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• v.42 no.4
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• pp.10-24
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• 2021

Objectives: Yongdamsagan-tang (YST) and Paljung-san (PJS) in traditional medicine and finasteride in modern medicine are used to treat benign prostatic hyperplasia (BPH). In recent, the use of combination herbal remedies with conventional drugs has been increasing. Therefore, we investigated the anti-inflammatory effects of these drugs to treat BPH and the influence of herbal formulas on finasteride metabolism. Methods: The inhibitory effects of the herbal formulas and finasteride on the production of inflammatory mediators and cytokines were determined in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Additionally, the influence of herbal formulas on activities of human drug metabolizing enzymes (DMEs) was assessed using human microsomal enzymes. Results: We observed that YST, PJS and finasteride inhibited the production of nitric oxide (NO), prostaglandin E₂ (PGE₂) and interleukin-6 (IL-6) in RAW 264.7 cells. The half maximal inhibitory concentration (IC₅₀) of YST on PGE₂ production was calculated to be below 25 ㎍/mL. YST inhibited the activity of uridine diphosphate-glucuronosyltransterase (UGT) 1A4 with an IC₅₀ value of 49.35 ㎍/mL. The activities of cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP3A4, and UGT1A1 were inhibited by PJS (IC₅₀ < 100 ㎍/mL, each). Although PJS and YST inhibited the activities of CYP3A4 and UGT1A4, respectively, these formulas may not influence the metabolism of finasteride because the IC₅₀ values of herbal formulas on DMEs are too high to affect metabolism. Conclusions: Our results suggest that the combination of finasteride and YST or PJS might not influence their drug metabolism and that the drugs may have synergistic effects against BPH.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.911-920
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• 2006

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.