• Development and Reproduction
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• v.10 no.3
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• pp.197-202
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• 2006

Sex steroids are generally considered as natural sex inducers in fish, and aromatase (cytochrome P450 aromatase) that catalyzes androgens into estrogens in the steroidogenic pathway is also known to be involved in sex differentiation. The timing of aromatase action is, thus, of central importance in the study of fish sex differentiation. We treated sexually undifferentiated tilapia (Oreochromis niloticus) larvae with $Fadrozole^{TM}$, a non-steroidal aromatase inhibitor (AI), by immersing the fish in a solution containing AI during the sex differentiation period to narrow down the critical period of aromatase action. Fish were treated once at 11 or 13 days post fertilization (dpf), or twice at 11 and 13 dpf. The concentrations of AI at each time of the treatment were 0 mg/L (control), 50 mg/L or 100 mg/L. Survival rate was not statistically associated with AI immersion treatment (p>0.25). However, sex ratio was significantly altered by the treatment, with higher concentration and double immersion being more effective in masculinizing genetic females (p<0.05). These results suggest that aromatase action for sex differentiation in this fish species would begin at least from 11 dpf which is much earlier than previously expected, and that only 3 hours of brief immersion in AI solution is powerful enough to alter genetically programed sex.

• The Korean Journal of Pharmacology
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• v.17 no.1 s.28
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• pp.17-25
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• 1981

No evidence has accumulated that lead compound is an essential component for biological function in animals. Lead is absorbed primarily through the epithelial mucosal cells in duodenum and the absorption can be enhanced by the substances which bind lead and increase its solubility. Iron, zinc and calcium ions, however, decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. Therefore, the absorption of lead is increased in iron deficient animals. Lead shows a strong affinity for ligands such as phosphate, cysteinyl and histidyl side chains of proteins, pterins and porphyrins. Hence lead can act on various active sites of enzymes, inhibiting the enzymes which has functional sulfhydryl groups. lead inhibits the activity of ${\delta}$-aminolevulinic acid dehydratase for the biosynthesis of hemoproteins and cytochrome, which catalyzed the synthesis of monopyrrole prophobilinogen from ${\delta}$-aminolevulinic acid. Accordingly lead decrease hepatic cytochrome p-450 content, resulting an inhibition of the activity of demethylase and hydroxylase in liver. Little informations are available on the effect of lead on digestive system although the catastrophic effects of lead intoxication are well documented. The present study was, therefore, attempted to investigate the effect of lead on pancreaticobiliary secretion in rats. Albino rats of both sexes weighing $170{\sim}230g$ were used for this study. The animals were divided into one control and three treated groups, i.e., control (physiologic saline 1.5ml/kg i.p.), lead acetate $(l0{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and EDTA$(each\;10{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and $FeSO_4(each\;l0{\mu}mole/kg/day\;hp)$. The pancreatico-biliary juice was collected under urethane anesthesia, and activities of amylase and lipase were determined by employing Sumner's and Cherry and Crandall's methods. The summarized results are follows. 1) In the experiment for acute toxicity of lead acetate, 20% of mortality was observed in rat treated with lead acetate as well as inhibition of the activity of amylase in the juice at the 3 rd day of the treatment. 2) No increases in body weight were observed in rats treated with lead acetate, while in control group the significant increases were observed. However, the body weights of animals were increased in the group lead acetate plus EDTA or $FeSO_4$. 3) Lead acetate decreased significantly the volume of pancreatico-biliary juice whereas additional treatment of EDTA and $FeSO_4$ prevented it. 4) Total activity of amylase was markedly reduced due to lead acetate treatment, but no change was showed following additional treatment with EDTA and $FeSO_4$. 5) No changes in the cholate and lipase output were observed in rats treated with lead acetate as compared with that of control rats. 6) Increase in bilirubin output in rats treated with lead acetate was shown on the 2nd and 3rd weeks treatment. 7) In the case of in vitro experiment, lead acetate also markedly inhibited release of amylase from pancreatic fragment. 8) Histologic finding indicated that acini vacuolation was induced in the pancreatic tissue of rat treated with lead acete. From the above results, it might be concluded that lead acetate decreases the volume of pancreatico-biliary secretion and inhibits the amylase activity, by acting directly on pancreatic cells.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.479-484
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• 2013

Given the CYP3A4 and CYP3A5's impact on the efficacy of drugs, the genetic backgrounds of individuals and populations are regarded as an important factor to be considered in the prescription of personalized medicine. However, genetic studies with Korean population are relatively scarce compared to those with other populations. In this study, we aimed to identify CYP3A4/5 polymorphisms and compare the genotype distributions among five ethnicities. To identify CYP3A4/5 SNPs, we first performed direct sequencing with 288 DNA samples which consisted of 96 Koreans, 48 European-Americans, 48 African-Americans, 48 Han Chinese, and 48 Japanese. The direct sequencing identified 15 novel SNPs, as well as 42 known polymorphisms. We defined the genotype distributions, and compared the allele frequencies among five ethnicities. The results showed that minor allele frequencies of Korean population were similar with those of the Japanese and Han Chinese populations, whereas there were distinct differences from European-Americans or African-Americans. Among the pharmacogenetic markers, frequencies of $CYP3A4^*1B$ (rs2740574) and $CYP3A5^*3C$ (rs776742) in Asian groups were different from those in other populations. In addition, minor allele frequency of $CYP3A4^*18$ (rs28371759) was the highest in Korean population. Additional in silico analysis predicted that two novel non-synonymous SNPs in CYP3A5 (+27256C>T, P389S and +31546T>G, I488S) could alter protein structure. The frequency distributions of the identified polymorphisms in the present study may contribute to the expansion of pharmacogenetic knowledge.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3925-3929
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• 2013

We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.781-784
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• 2016

The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.768-774
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• 1999

Background: It is well known that rifampin decreases the hypoprothrombinemic effect of warfarin by induction of cytochrome P-450 enzyme in healthy volunteer. However, in patients the dosage schedule of warfarin during rifampin therapy is not established. Therefore, patients taking both rifampin and warfarin were reviewed to find out the adequate dosage schedule of warfarin in addition to side effects by interaction of two drugs. Method: Patients taking both rifampin and warfarin were retrieved from patients who were admitted due to heart disease and tuberculosis at Boochun Sejong Hospital from January of 1995 to August of 1999. To decide the adequate dosage of warfarin, the dosage of warfarin before, during, and after rifampin was evaluated in patients who kept adequate hypoprothrombinemic effect of warfarin during rifampin. To decide the adequate dosage schedule of warfarin, the time interval from the beginning of rifampin to normalization of prothrombin time(INR$\geq$1.1) was evaluated. And, the side effects by interaction of two drugs were reviewed. Results: All 12 patients taking both rifampin and warfarin were retrieved. Among them only 6 kept adequate hypoprothrombinemic effect of warfarin during rifampin. The dosage of warfarin during rifampin was $2.4{\pm}0.6$(mean$\pm$standard deviation) times as much as that before rifampin but the dosage after rifampin was the same as that before rifampin. The time interval from the beginning of rifampin to normalization of prothrombin time was $5.8{\pm}2.9$(mean${\pm}$standard deviation) days. 2 out of 12 had complication related to the interaction of rifampin and warfarin, one cerebral embolism just after the beginning of rifampin and the other cerebral hemorrhage just after the discontinuation of rifampin. Conclusion: When both rifampin and warfarin are prescribed, it would be a possible method to be confirmed by prospective study that warfarin be gradually increased about 2 times more than that without rifampin over 1 week or so after the beginning of rifampin and be tapered to the same dosage as that before rifampin when rifampin is discontinued. And, it would be prudent that prothrombin time be monitored frequently during rifampin and warfarin therapy, especially the beginning or discontinuation of rifampin.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.8
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• pp.1099-1106
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• 2011

Cucumber fermentation has been used as a means of preservation. This study was performed to investigate the effects of fermented cucumber beverage (CF) containing beneficial materials for an ethanol hangover based on Hovenia dulcis (SKM) on ethanol-induced hepatotoxicity. Male Sprague-Dawley rats were randomly divided into three groups: ethanol control, ethanol plus SKM, and ethanol plus CF+SKM. SKM or CF+SKM was orally administered at a dose of 7 mL/kg body weight once per day for 5 weeks. Control rats were given an equal amount of water. CF+SKM significantly lowered plasma ethanol levels, whereas SKM tended to decrease the levels compared to the control. Both SKM and CF+SKM significantly lowered the plasma acetaldehyde levels and serum transaminase activities compared to those in the control. SKM and CF+SKM did not affect hepatic alcohol dehydrogenase activity; however, it significantly inhibited cytochrome P450 2E1 (CYP2E1) activity. Hepatic aldehyde dehydrogenase (ALDH) activity was significantly higher in the SKM and CF+SKM groups than that in the control group. Plasma acetaldehyde concentration was significantly correlated with hepatic CYP2E1 (r=0.566, p<0.01) activity and ALDH (r=-0.564, p<0.01) activity. Hepatic superoxide dismutase and catalase activities as well as glutathione content increased with the SKM and CF+SKM administration, whereas lipid peroxide content decreased significantly. Furthermore, SKM and CF+SKM lowered plasma and hepatic lipid content and lipid droplets compared to those in the control group. These results indicate that SKM and CF+SKM exhibit hepatoprotective properties partly by inhibiting CYP2E1 activity, enhancing ALDH activity and stimulating the antioxidant defense systems in ethanol-treated rats.

• Journal of Life Science
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• v.28 no.7
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• pp.835-840
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• 2018

Quantitative determination of the protein expression levels is one of the most important parts in assessment of the safety of foods derived from genetically modified (GM) crops. Overexpression of AtCYP78A7, a gene encoding cytochrome P450 protein, has been reported to improve tolerance to abiotic stress, such as drought and salt stress, in transgenic rice (Oryza sativa L.). In the present study, an enzyme-linked immunosorbent assay (ELISA) kit for diagnosing AtCYP78A7 protein including AtCYP78A7-specific monoclonal antibody was developed. GST-AtCYP78A7 recombinant protein was induced and purified by affinity column. Four monoclonal antibodies (mAb 6A7, mAb 4C2, mAb 11H6, and mAb 7E8) against recombinant protein were also produced and biotinylated with avidin-HRP. After pairing test using GST-AtCYP78A7 protein and lysate of rice samples, mAb 4C2 and mAb 7E8 were selected as a capture antibody and a detecting antibody, respectively, for ELISA kit. Product test using rice samples indicated that percentages of detected protein in total protein were greater than 0.1% in AtCYP78A7-overexpressing transgenic rice (Line 10B-5 and 18A-4), whereas those in negative control non-transgenic rice (Ilpum and Hwayoung) were less than 0.1%. The ELISA kit developed in this study can be useful for the rapid detection and safety assessment of transgenic rice overexpressing AtCYP78A7.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4689-4695
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• 2014

Background: A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancers susceptibility in Chinese populations. Materials and Methods: Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed-effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Results: Eighteen case-control studies with 1,747 cases and 2,923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancers risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Conclusions: Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancers risk in Chinese populations. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.31-35
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• 2020

Objective: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are frequently prescribed medications worldwide for the treatment of hypercholesterolemia. Statins are considered to be well tolerated; however, they have a potential for myotoxicity. Concomitant drugs that inhibit cytochrome P450 3A4 can increase the concentration of statins and thus the risk of developing myotoxicity. The purpose of this study was to evaluate risk factors associated with potential drug-drug interactions in patients receiving statins. Methods: The subjects of this study were patients aged more than 18 years who received at least one prescription of statins in a general hospital located in Chuncheon-si, Korea, between January 1, 2018, and March 31, 2018. Data regarding statin use and baseline characteristics was collected from the computerized hospital database. Logistic regression analysis was used to identify risk factors associated with potential drug-drug interactions. Results: A total of 1061 patients were finally included in the study. The incidence of potential drug-drug interactions was 45% in all subjects. According to the results of the multivariate logistic regression analysis, myocardial infarction as the indication of statin, arrhythmia or heart failure as a comorbidity, and aspartate aminotransferase levels higher than 40 IU/L were significant risk factors for potential drug-drug interactions in study subjects. Diltiazem was the most commonly co-prescribed drug that caused potential drug-drug interactions with statins. Conclusion: There was a considerable rate of potential drug-drug interactions in patients receiving statins. Health care professionals should attempt to reduce potential drug-drug interactions during statin administration.