• Archives of Pharmacal Research
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• 제13권3호
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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.

• 대한수의학회지
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• 제43권4호
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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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2006년도 Proceedings of The Convention
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• pp.51-66
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• 2006

The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2006년도 Proceedings of The Convention of The Korean Society of Applied Pharmacology
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• pp.51-66
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• 2006

The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.36-41
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• 1996

Drugs mean not only medicines but also poisons, pesticides, food additives, cosmetics, cleaning agents, environmental pollutants and so on, which are normally considered foreign to the body, It is important to know what happens to these drugs when they get into the body. In the past the metabolic changes of drugs had been referred to as “detoxication mechanism”, but since there are many instances in which drugs are converted in the body to more active substances. Thus, metabolism of drugs is responsible for activation and inactivation of the drugs in the body. The major reactions in drug metabolism are oxidation, reduction, hydrolysis and conjugation. Of these four areas, most of the attention had been focused on the oxidation. Therefore, in contract of ample literatures on drug-oxidizing enzymes, there were relatively few reports on drug-reducing enzymes. In recent years, however, the reduction has received an increasing interest due to its pharmacological or toxicological significance. The present lecture is organized keeping with a focus on drug-reducing enzymes which have been explored by us and by other groups.

• 대한한의학회지
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• 제42권4호
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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.

• 생약학회지
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• 제24권1호
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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.

• Food Science and Biotechnology
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• 제16권3호
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• pp.439-443
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• 2007

The effects of the methanol extract of the leaves of Brassica juncea and isorhamnetin $3-O-{\beta}-D-glucopyranoside$, major compound isolated from the ethyl acetate fraction of this plant on hepatic lipid peroxidation and drug-metabolizing enzymes, were evaluated in rats treated with bromobenzene. The extract and isorhamnetin $3-O-{\beta}-D-glucopyranoside$ of oral administration did not show any significant effects on activities of aminopyrine N-demethylase and aniline hydroxylase, enzymes forming toxic epoxide by bromobenzene as well as on glutathione content. However, both methanol extract and isorhamnetin $3-O-{\beta}-D-glucopyranoside$ significantly recovered the decreased activities of glutathione s-transferase and epoxide hydrolase, and also reduced the lipid peroxide level in rats treated with bromobenzene. From the results, the protections of this plant against bromobenzene-induced hepatotoxicity are thought to be via enhancing the activities of epoxide hydrolase and glutathione s-transferase, enzymes removing toxic epoxide, and reducing the lipid peroxide level.

• Archives of Pharmacal Research
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• 제29권10호
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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.

• 한국어병학회지
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• 제36권2호
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• pp.337-348
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• 2023

본 연구에서는 넙치의 해독 과정에서 amprolium hydrochloride의 영향을 평가하기 위해 수행되었다. 이전 연구에서 보고된 amprolium의 LD₅₀ 값을 이용하여 두 가지 실험을 진행하였다. 첫 번째는 30마리의 넙치를 5개의 대조군 및 실험군으로 나누었고 4, 8, 16, 32 mg/kg 용량의 amprolium을 근육 내 주사 투여하였다. 주사 후 8, 24, 48 시간에 간과 신장을 적출하여 약물 대사 효소와 전염증성 사이토카인 유전자의 발현을 분석하였다. 32 mg/kg 용량의 실험군에서 IL-1β mRNA의 높은 발현을 확인하였고, CYP1A는 이와 반대의 결과를 보였으며, 간에서 UGT와 GST mRNA의 발현은 유의하게 감소하는 것을 확인하였다. 또한 신장에서 amprolium 주사 투여 후 약물 대사 효소와 사이토카인 유전자의 억제가 관찰되었다. 또 다른 실험에서는 4, 8, 16, 32 mg/kg과 60, 80, 100, 120 mg/kg의 용량을 설정하여 근육 내 주사 투여하였다. 주사를 완료하고 6일 후 간을 적출하여 유전자의 발현을 확인하였다. IL-1β의 발현은 4 mg/kg 용량 실험군에서 유의적으로 매우 높은 발현을 보였다. GST의 mRNA 발현 또한 4 mg/kg 용량 실험군에서 높은 발현을 보였다. 결론적으로 우리의 결과는 amprolium이 가축 산업의 가장 안전한 합성 항콕시듐 약물 중 하나로 간주되지만 넙치의 간접 또는 직접적인 물리적 또는 생물학적 독성을 유발하는 것으로 판단된다.