• Korean Journal of Veterinary Research
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• v.60 no.4
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• pp.215-223
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• 2020

Sasa (S.) quelpaertensis Nakai (Korean name, Jeju-Joritdae), which has anti-oxidative and anti-inflammatory activities, is a type of bamboo grass distributed widely in Jeju Island, Korea. S. quelpaertensis leaves are used for therapeutic purposes in traditional Korean medicine. This study examined the hepatoprotective effects of the S. quelpaertensis ethyl acetate fraction (SQEA) in a mouse model to mimic alcoholic liver damage. The mice were administered orally with 30% alcohol (5 g/kg) once per day with or without SQEA treatments (100 and 200 mg/kg) for 14 days consecutively. Alcohol consumption increased the serum alcohol content and histopathological changes but reduced the liver weight. Moreover, the livers of the alcohol group exhibited the accumulation of malondialdehyde and cytochrome P450 2E1 (CYP2E1), and lipid droplet coating protein perilipin-2. On the other hand, SQEA dose-dependently attenuated the alcohol-induced serum ethanol content and liver histopathological changes but increased the liver weight. Moreover, SQEA attenuated the level of CYP2E1 and inhibited alcohol-induced lipogenesis in the liver via decreased perilipin-2 expression. These results suggest that SQEA can provide a potent way to reduce the liver damage caused by alcohol consumption.

• 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.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.55-63
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• 1982

Lipid peroxidation is the reaction of oxidative deterioration of polyunsaturated lipids and this peroxidation involves the direct reaction of oxygen and lipid to form free radical intermediates, which can lead to autocatalysis. As results of the extensive studies on the lipid peroxidation by many authors, the relationship between lipid peroxidation and the drug metabolizing system as well as the actions of free radicals on the peroxidation was reasonably well known. For a long time, the mechanism of hepatotoxicity of $CCl_4$ was not clearly understood. However, it is now quite well established that $CCl_4$ is activated in vivo to a free radical which is a highly reactive molecule. Therefore, lipid peroxidation which induces the reduction of cytochrome P-450 and aminopyrine demethylase activity is known as decisive event of $CCl_4$ hepatotoxicity. On the other hand, it was also reported that singlet molecular oxygen produces lipid peroxidation in liver microsomes. In this study the effects of benzoyl peroxide on the lipid peroxidation and drug-metabolizing enzyme were examined. Benzoyl peroxide mixed with starch and phosphates etc. is usually used as a food additive for flour bleaching and maturing purpose because of its oxidative property. Albino rats were used for the experimental animals. Benzoyl peroxide was suspended in soybean oil and sesame oil and administered intraperitoneally or orally. TBA value and aminopyrine demethylase activity were determined in liver microsomal fraction and serum. The results were summerized as following. 1) Body weights of animals administered benzoyl peroxide suspension were decreased while that of oil administered group were increased. 2) The activity of aminopyrine demethylase was generally decreased in animals administered oil suspension of benzoyl peroxide. Furthermore, the marked reduction of the enzyme activity was observed in animals administered benzoyl peroxide intraperitoneally. 3) Generally, microsomal TBA values as well as serum TBA were significantly elevated in benzoyl peroxide group in comparison with the control group. However, the more remarkable increase of serum TBA than microsomal TBA was observed in animals administered orally for 6 days. 4) Specifically, the changing pattern of TBA value was notable in serum rather than in liver microsome by intraperitoneal administration of benzoyl peroxide.

• Korean Journal of Biological Psychiatry
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• v.18 no.2
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• pp.95-100
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• 2011

Objectives To evaluate the drug interactions between aripiprazole and haloperidol, authors investigated plasma concentrations of those drugs by genotypes. Method Fifty six patients with a confirmed Diagnostic and Statistical Manual of Mental Disorders 4th edition diagnosis of schizophrenia were enrolled in this eight-week, double blind, placebo-controlled study. Twenty-eight patients received adjunctive aripiprazole treatment and twenty-eight patients received placebo while being maintained on haloperidol treatment. Aripiprazole was dosed at 15 mg/day for the first 4 weeks, and then 30 mg for the next 4 weeks. The haloperidol dose remained fixed throughout the study. Plasma concentrations of haloperidol and aripiprazole were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, week 1, 2, 4 and 8. $^*1$, $^*5$, and $^*10$ B alleles of CYP2D6 and $^*1$ and $^*3$ alleles of CYP3A5 were determined. The Student's T-test, Pearson's Chi-square test, Wilcoxon Rank Sum test and Logistic Regression analysis were used for data analysis. All tests were two-tailed and significance was defined as an alpha < 0.05. Results In the frequency of CYP2D6 genotype, $^*1/^*10$ B type was most frequent (36.5%) and $^*1/^*1$ (30.8%), $^*10B/^*10B$ (17.3%) types followed. In the frequency of CYP3A5 genotype, $^*3/^*3$ type was found in 63.5% of subjects, and $^*1/^*3$ type and $^*1/^*1$ were 30.8% and 5.8% respectively. The plasma levels of haloperidol and its metabolites did not demonstrate significant time effects and time-group interactions after adjunctive treatment of aripiprazole. The genotypes of CYP2D6 and 3A5 did not affect the plasma concentration of haloperidol in this trial. No serious adverse event was found after adding aripiprazole to haloperidol. Conclusion No significant drug interaction was found between haloperidol and aripiprazole. Genotypes of CYP2D6 and 3A5 did not affect the concentration of haloperidol after adding aripiprazole.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.124-124
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• 2017

Cadmium (Cd) is of particular concern because of its widespread occurrence and high toxicity and may cause serious morpho-physiological and molecular abnormalities in in plants. The present study was performed to explore Cd-induced morpho-physiological alterations and their potentiality associated mechanisms in Sorghum bicolor leaves at the protein level. Ten-day-old sorghum seedlings were exposed to different concentrations (0, 100, and $150{\mu}M$) of $CdCl_2$, and different morpho-physiological responses were recorded. The effects of Cd exposure on protein expression patterns in S. bicolor were investigated using two-dimensional gel electrophoresis (2-DE) in samples derived from the leaves of both control and Cd-treated seedlings. The observed morphological changes revealed that the plants treated with Cd displayed dramatically altered shoot lengths, fresh weights, and relative water content. In addition, the concentration of Cd was markedly increased by treatment with Cd, and the amount of Cd taken up by the shoots was significantly and directly correlated with the applied level of Cd. Using the 2-DE method, a total of 33 differentially expressed protein spots were analyzed using MALDI-TOF/TOF MS. Of these, treatment with Cd resulted in significant increases in 15 proteins and decreases in 18 proteins. Significant changes were absorbed in the levels of proteins known to be involved in carbohydrate metabolism, transcriptional regulation, translation and stress responses. Proteomic results revealed that Cd stress had an inhibitory effect on carbon fixation, ATP production and the regulation of protein synthesis. In addition, the up-regulation of glutathione S-transferase and cytochrome P450 may play a significant role in Cd-related toxicity and stress responses. Our study provides insights into the integrated molecular mechanisms involved in response to Cd and the effects of Cd on the growth and physiological characteristics of sorghum seedlings. The upregulation of these stress-related genes may be candidates for further research and use in genetic manipulation of sorghum tolerance to Cd stress.

• 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.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.24-24
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• 2017

Heavy metals at toxic levels have the capability to interact with several vital cellular biomolecules such as nuclear proteins and DNA, leading to oxidative stress in plants. The present study was performed to explore the metal tolerance mechanism in Sorghum seedling. Morpho-physiological and metal ions uptake changes were observed prominently in the seedlings when the plants were subjected to different concentrations of $CuSO_4$ and $CdCl_2$. The observed morphological changes revealed that the plants treated with Cu and Cd displayed dramatically altered shoot lengths, fresh weights, and relative water content. In addition, the concentration of Cu and Cd was markedly increased by treatment with Cu and Cd, and the amount of interacting ions taken up by the shoots and roots was significantly and directly correlated with the applied level of Cu and Cd. Using the 2-DE method, a total of 24 and 21 differentially expressed protein spots from sorghum leaves and roots respectively, 33 protein spots from sorghum leaves under Cd stress were analyzed using MALDI-TOF/TOF MS. However, the over-expression of GAPDH plays a significant role in assisting Sorghum bicolor to attenuate the adverse effects of oxidative stress caused by Cu, and the proteins involved in resistance to stress helped the sorghum plants to tolerate high levels of Cu. Significant changes were absorbed in the levels of proteins known to be involved in carbohydrate metabolism, transcriptional regulation, translation and stress responses. In addition, the up-regulation of glutathione S-transferase and cytochrome P450 may play a significant role in Cd-related toxicity and stress responses. The results obtained from the present study may provide insights into the tolerance mechanism of seedling leaves and roots in Sorghum under heavy metal stress.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.7 no.1
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• pp.61-69
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• 1997

To evaluate an effect of pathological liver damage on the toluene metabolism, the rate were induced acute liver damage with 3 times $CCl_4$ injection (0.1 ml of 50 % in olive oil/100 g body wt.) three days. In the present animal molel, the injection of toluene(0.3 ml of 50 % in olive oil) showed the more decreased urine hippuric acid throughout 24 hr in the liver damage induced animals($CCl_4$-pretreated rats) than normal group. The activities of hepatic aniline hydroxylase, benzylalcohol dehydrogenase and benzaldehyde dehydrogenase were significantly decreased in $CCl_4$-pretreated rats than the normal group at 24 hr after injection of toluene. Furthermore, the benzaldehyde dehydrogenase in pooled liver of $CCl_4$-pretreated rats showed similiar $K_m$ value, but showed the more decreased $V_{max}$ value compared with the normal group by the injection of toluene. These results suggest that the rats induced liver damage with $CCl_4$ may reduce the toluene metabolism.