16 results on '"Jun-Won Yun"'
Search Results
2. Transcriptomic analysis of rat kidney reveals a potential mechanism of sex differences in susceptibility to cisplatin-induced nephrotoxicity
- Author
-
Da-Bin Hwang, Yoo-Sub Shin, Min Ho Cha, Changuk Kim, Eun-Ji Lee, Shin-Young Kim, Dong-Hoon Won, Yoon Young Kim, and Jun-Won Yun
- Subjects
Male ,medicine.medical_treatment ,Intraperitoneal injection ,Antineoplastic Agents ,Pharmacology ,Kidney ,Biochemistry ,Nephrotoxicity ,Transcriptome ,Mice ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,Physiology (medical) ,medicine ,Animals ,Blood urea nitrogen ,Tissue homeostasis ,Cisplatin ,Sex Characteristics ,Creatinine ,business.industry ,Rats ,chemistry ,Apoptosis ,Female ,business ,medicine.drug - Abstract
Although cisplatin is an effective platinum-based anticancer drug against solid cancer, its availability is limited owing to its adverse side effects. Our study aimed to identify the potential relationship within cisplatin-induced multi-organ physiological changes and genetic factors associated with sex differences in nephrotoxicity susceptibility. To investigate this, mice received a single intraperitoneal injection of cisplatin. Cisplatin administration resulted in renal dysfunction, as evidenced by the elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine) and the degree of histopathological alterations. In particular, along with testicular damage and low testosterone levels, we also observed a decrease in male-specific (CYP3A2) or male-dominant (CYP2B1 and CYP3A1) CYP isoforms in the livers of rats with hepatotoxicity following cisplatin treatment, which may be associated with an imbalance in male hormone regulation caused by renal and testicular injury. Notably, we found that male rats were more susceptible to cisplatin-induced nephrotoxicity, as characterized by histopathological and biochemical analyses. Therefore, RNA sequencing was performed at baseline (pre-treatment) and at 48 h following cisplatin administration (post-treatment) to identify the genes associated with sex differences in nephrotoxicity susceptibility. Gap junctions, which play a role in replenishing damaged cells to maintain tissue homeostasis, and mismatch repair associated with a pathological apoptotic mechanism against cisplatin nephrotoxicity were significantly enriched only in males following cisplatin treatment. Moreover, among the 322 DEGs showing different basal expression patterns between males and females before cisplatin treatment, the male expressed high levels of genes, which are responsible for transmembrane transport and regulation of apoptotic process, pre-cisplatin treatment; additionally, genes involved in the PI3K-Akt signaling pathway and the oxidation–reduction process were significantly lower in males before cisplatin treatment. Collectively, our comprehensive findings provided valuable insight into the potential mechanisms of sex differences in cisplatin-induced nephrotoxicity susceptibility.
- Published
- 2021
3. Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea
- Author
-
Hyuna Noh, Suhyeon Yoon, Sung-Hee Kim, Jiseon Kim, Jung Seon Seo, Jeong Jin Kim, In Ho Park, Jooyeon Oh, Joon-Yong Bae, Gee Eun Lee, Sun-Je Woo, Sun-Min Seo, Na-Won Kim, Youn Woo Lee, Hui Jeong Jang, Seung-Min Hong, Se-Hee An, Kwang-Soo Lyoo, Minjoo Yeom, Hanbyeul Lee, Bud Jung, Sun-Woo Yoon, Jung-Ah Kang, Sang-Hyuk Seok, Yu Jin Lee, Seo Yeon Kim, Young Been Kim, Ji-Yeon Hwang, Dain On, Soo-Yeon Lim, Sol Pin Kim, Ji Yun Jang, Ho Lee, Kyoungmi Kim, Hyo-Jung Lee, Hong Bin Kim, Sun Bean Kim, Jun Won Park, Dae Gwin Jeong, Daesub Song, Kang-Seuk Choi, Ho-Young Lee, Yang-Kyu Choi, Jung-ah Choi, Manki Song, Man-Seong Park, Jun-Young Seo, Jeon-Soo Shin, Jun-Won Yun, Ki Taek Nam, and Je Kyung Seong
- Subjects
Pulmonary and Respiratory Medicine ,Biochemistry (medical) ,Pharmacology (medical) - Published
- 2023
4. Genotoxic carcinogen 7,12-dimethylbenz[a]anthracene inhibits gap junction intercellular communication through post-transcriptional and post-translational processing involved in connexin 43 stability
- Author
-
Dong-Hoon Won, Da-Bin Hwang, Changuk Kim, MinHwa Kang, Young Jeon, Yong Il Park, Jeong-Hwan Che, and Jun-Won Yun
- Subjects
General Medicine ,Toxicology ,Food Science - Published
- 2023
5. Clinical characteristics of diabetic ketoacidosis in users and non-users of SGLT2 inhibitors
- Author
-
S.O. Song, Da Hea Seo, Soon-Sun Hong, Bo Yeon Kim, Jung Hyun Noh, Dae Jung Kim, Chul-Hee Kim, S.O. Park, K.-S. Kim, Ji A Seo, Jun-Won Yun, Ja Young Jeon, and S.-K. Kim
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,endocrine system diseases ,Diabetic ketoacidosis ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Non users ,Diabetic Ketoacidosis ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,law ,Internal medicine ,Diabetes Mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,In patient ,Hospital Mortality ,Sodium-Glucose Transporter 2 Inhibitors ,Retrospective Studies ,Plasma glucose ,business.industry ,Medical record ,Mortality rate ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,medicine.disease ,Intensive care unit ,Treatment Outcome ,Female ,business - Abstract
Aim This study investigated the clinical characteristics of diabetic ketoacidosis (DKA) and compared the DKA characteristics between patients treated with and without SGLT2 inhibitors. Methods Data were collected from patients aged ≥ 18 years admitted for DKA at nine centres in Korea between September 2014 and April 2017. The electronic medical records of these subjects were retrospectively reviewed. Based on their history of medications taken before admission, subjects were classified as either users or non-users of SGLT2 inhibitors and their clinical characteristics of DKA were compared. Results During the study, the main subtype of DKA episodes (n = 523) was identified as type 2 diabetes (51%). Average hospitalization duration was 11 days, and average intensive care unit (ICU) time was 2.5 days. The in-hospital mortality rate was 3%, but no users of SGLT2 inhibitors died during DKA treatment. In patients taking SGLT2 inhibitors (n = 15), DKA manifested at 124 days, on average, after starting the inhibitors (range: 7–380 days). Also, SGLT2 inhibitors users had significantly lower plasma glucose levels (413 mg/dL) compared with non-users (554 mg/dL), and longer ICU stays (4 vs. 2 days; P = 0.019). Conclusion In this report of recent data on the clinical features of DKA in Korea, patients using SGLT2 inhibitors needed longer treatment in ICUs compared with non-users and had lower levels of blood glucose, whereas DKA associated with SGLT2 inhibitors was rare.
- Published
- 2019
6. Use of stem cells as alternative methods to animal experimentation in predictive toxicology
- Author
-
Jeong Hwan Che, Jun Won Yun, and Tae Won Kim
- Subjects
Animal Experimentation ,Induced Pluripotent Stem Cells ,Developmental toxicity ,Computational biology ,010501 environmental sciences ,Biology ,Animal Testing Alternatives ,Toxicology ,030226 pharmacology & pharmacy ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,Species Specificity ,Toxicity Tests ,Animals ,Humans ,Animal testing ,Induced pluripotent stem cell ,0105 earth and related environmental sciences ,Stem Cells ,Mesenchymal stem cell ,Cell Differentiation ,General Medicine ,Embryonic stem cell ,Stem cell ,Immortalised cell line ,Adult stem cell - Abstract
Despite a major role of experimental animals in development of biomedical research, there has been historical controversy surrounding animal research. Along with a strategy of 3Rs, various in vitro methods have been suggested to replace potentially painful animal experiments. In this review, we summarize the use of stem cells as an alternative of animal experimentation in predictive toxicology. There have been continuing researches on stem cells and stem cell-derived tissue-specific cells to develop alternative methods/biomarkers for animal toxicity testing including developmental toxicity, genotoxicity, and tissue-specific toxicity. Along with unique abilities of stem cells including self-renewal, infinite proliferation, and differentiation into multiple lineages, human stem cell-based in vitro systems have been proven valuable to increase predictive power of toxicology through providing with better scientific information related to toxic risks in humans without inter-species variability. In particular, stem cells including induced pluripotent stem cell-based system for personalized toxicological assessment could be a better option as an in vitro model system in comparison with immortalized cells with abnormal phenotype or primary cells with small quantity and batch-to-batch variation. This review will be useful for understanding the current status and future direction in using stem cells as an alternative non-animal method for predictive toxicology.
- Published
- 2019
7. In vitro and in vivo safety studies of cinnamon extract ( Cinnamomum cassia ) on general and genetic toxicology
- Author
-
Seung Hyun Kim, Euna Kwon, Jin-Sung Park, Hyoung Chin Kim, Yun Soon Kim, Ja June Jang, Jun Won Yun, Eun Young Cho, Jeong Hwan Che, Jung Hee Yoon, Byeong Cheol Kang, and Ji Ran You
- Subjects
Male ,0301 basic medicine ,Kidney ,Toxicology ,medicine.disease_cause ,Nephrotoxicity ,Ames test ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Cassia ,Toxicity Tests, Acute ,Animals ,Medicine ,biology ,Traditional medicine ,Mutagenicity Tests ,Plant Extracts ,business.industry ,Toxicity Tests, Subchronic ,Cinnamomum aromaticum ,Organ Size ,General Medicine ,biology.organism_classification ,Rats, Inbred F344 ,030104 developmental biology ,Liver ,030220 oncology & carcinogenesis ,Micronucleus test ,Toxicity ,Plant Bark ,Female ,business ,Genotoxicity ,Cinnamomum - Abstract
Cinnamomum cassia has been widely used as a natural product to treat diseases in Asia due to its diverse pharmacological functions including anti-inflammatory, anti-oxidant, anti-microbial, anti-diabetic, and anti-tumor effects. Despite its ethnomedicinal benefits, little information regarding its toxicity is currently available. The aim of this study was to evaluate its potential long-term toxicity and genotoxicity in compliance with test guidelines of the Organization for Economic Cooperation and Development. A 13-week repeat-dose oral toxicity study revealed that body weights of rats were normal after receiving cinnamon extract at up to 2000 mg/kg. High-dose intake of cinnamon extract (2000 mg/kg) showed potential nephrotoxicity and hepatotoxicity to both males and females as evidenced by obvious increases of kidney/liver weight along with a small but statistically elevation of total cholesterol level. Overall findings from genetic toxicity testing battery including Ames test, in vitro mammalian cell micronucleus assay, and in vivo bone marrow micronucleus assay indicated that cinnamon extract was not mutagenic or clastogenic. In conclusion, cinnamon extract may possess potential nephrotoxicity and hepatotoxicity at dose higher than its recommended daily safe dose. Further study is needed to clarify the mechanism involved in its induction of liver and kidney injury.
- Published
- 2018
8. A comprehensive study on in vitro and in vivo toxicological evaluation of Artemisia capillaris
- Author
-
Yun Soon Kim, Jeong Hwan Che, Jung Hee Yoon, Byeong Cheol Kang, Seung Hyun Kim, Jae Hun Ahn, Euna Kwon, Ja June Jang, Jun Won Yun, Ji Ran You, and Eun Young Cho
- Subjects
Male ,0301 basic medicine ,No-observed-adverse-effect level ,Drinking ,Administration, Oral ,Pharmacology ,Toxicology ,medicine.disease_cause ,Chromosome aberration ,Ames test ,Rats, Sprague-Dawley ,Eating ,03 medical and health sciences ,0302 clinical medicine ,Oral administration ,medicine ,Animals ,No-Observed-Adverse-Effect Level ,Micronucleus Tests ,biology ,Plant Extracts ,Chemistry ,Body Weight ,Toxicity Tests, Subchronic ,Organ Size ,General Medicine ,biology.organism_classification ,Rats ,030104 developmental biology ,Artemisia ,030220 oncology & carcinogenesis ,Toxicity ,Micronucleus test ,Female ,Genotoxicity - Abstract
Artemisia capillaris (AC) has been used as an alternative therapy in obesity, atopic dermatitis, and liver diseases through several biological activity including anti-steatotic, antioxidant, and anti-inflammatory activities. Despite its ethnomedicinal benefits, no sufficient background information is available about the long-term safety and genotoxicity of the AC extract. Therefore, the present study was carried out to investigate the 13-week subchronic toxicity and genotoxicity of the AC extract according to the test guidelines published by the Organization for Economic Cooperation and Development. In the 13-week toxicity study using doses of 25, 74, 222, 667, and 2000 mg/kg body weight, oral administration of the AC extract in male and female rats did not result in any significant adverse effects in food/water consumption, body weight, mortality, hematology, serum biochemistry, organ weight and histopathology. Accordingly, the no-observed-adverse-effect level in rats of both genders was established for the AC extract at 2000 mg/kg/day, the highest dose level tested. In addition, the AC extract was not genotoxic in a battery of tests including Ames test, in vitro chromosome aberration assay and in vivo micronucleus assay. In conclusion, we demonstrated that the AC extract is considered as a safe traditional medicine for human consumption.
- Published
- 2017
9. Advances in selecting appropriate non-rodent species for regulatory toxicology research: Policy, ethical, and experimental considerations
- Author
-
Jeong Hwan Che, Byeong Cheol Kang, Ha Ni Choi, Jun Won Yun, and Yong Wook Son
- Subjects
Background data ,General Medicine ,Computational biology ,010501 environmental sciences ,Biology ,Toxicology ,030226 pharmacology & pharmacy ,01 natural sciences ,Clinical trial ,Toxicology studies ,03 medical and health sciences ,Experimental animal ,0302 clinical medicine ,Regulatory toxicology ,Expression pattern ,Research Design ,Models, Animal ,Research policy ,Animals ,Animal studies ,0105 earth and related environmental sciences - Abstract
In vivo animal studies are required by regulatory agencies to investigate drug safety before clinical trials. In this review, we summarize the process of selecting a relevant non-rodent species for preclinical studies. The dog is the primary, default non-rodent used in toxicology studies with multiple scientific advantages, including adequate background data and availability. Rabbit has many regulatory advantages as the first non-rodent for the evaluation of reproductive and developmental as well as local toxicity. Recently, minipigs have increasingly replaced dogs and rabbits in toxicology studies due to ethical and scientific advantages including similarity to humans and breeding habits. When these species are not relevant, nonhuman primates (NHPs) can be used as the available animal models, especially in toxicology studies investigating biotherapeutics. Particularly, based on the phylogenetic relationships, the use of New-World marmosets can be considered before Old-World monkeys, especially cynomolgus with robust historical data. Importantly, the use of NHPs should be justified in terms of scientific benefits considering target affinity, expression pattern, and pharmacological cross-reactivity. Strict standards are required for the use of animals. Therefore, this review is helpful for the selection of appropriate non-rodent in regulatory toxicology studies by providing sufficient regulatory, ethical, and scientific data for each species.
- Published
- 2020
10. Safety evaluation of Angelica gigas: Genotoxicity and 13-weeks oral subchronic toxicity in rats
- Author
-
Euna Kwon, Jun Won Yun, Jeong Hwan Che, Byeong Cheol Kang, Yun Soon Kim, Ji Ran You, Seung Hyun Kim, Hyeon Hoe Kim, and Woo Ho Kim
- Subjects
Male ,Salmonella typhimurium ,No-observed-adverse-effect level ,Pharmacology ,Toxicology ,medicine.disease_cause ,Plant Roots ,Chromosome aberration ,Cell Line ,Ames test ,Cricetulus ,Animals ,Medicine ,Adverse effect ,Angelica ,Mice, Inbred ICR ,No-Observed-Adverse-Effect Level ,biology ,Mutagenicity Tests ,Plant Extracts ,business.industry ,Toxicity Tests, Subchronic ,General Medicine ,biology.organism_classification ,Rats, Inbred F344 ,Toxicity Tests, Subacute ,Angelica gigas ,Toxicity ,Micronucleus test ,Female ,business ,Genotoxicity - Abstract
As a well-known traditional medicine, Angelica gigas (AG) and its active constituents, including decursin and decursinol, have been shown to possess several health beneficial properties such as anti-bacterial, immunostimulating, anti-tumor, neuroprotective, anti-nociceptive and anti-amnestic activities. However, there is lack of toxicity studies to assess potential toxicological concerns, especially long-term toxicity and genotoxicity, regarding the AG extract. Therefore, the safety of AG extract was assessed in subchronic toxicity and genotoxicity assays in accordance with the test guidelines published by the Organization for Economic Cooperation and Development. In a subchronic toxicity study for 13 weeks (125, 250, 500, 1000 and 2000 mg/kg body weight, delivered by gavage), data revealed no significant adverse effects of the AG extract in food consumption, body weight, mortality, hematology, biochemistry, necropsy, organ weight and histopathology throughout the study in male and female rats. These results suggest that no observed adverse effect level of the AG extract administered orally was determined to be greater than 2000 mg/kg/day, the highest dose tested. In addition, a battery of tests including Ames test, in vitro chromosome aberration assay and in vivo micronucleus assay suggested that the AG extract was not genotoxic. In conclusion, the AG extract appears to be safe as a traditional medicine for oral consumption.
- Published
- 2015
11. Toxicologic assessment of Paecilomyces tenuipes in rats: Renal toxicity and mutagenic potential
- Author
-
Seung Hyun Kim, Eun Young Cho, Jun Won Yun, Woo Ho Kim, Jeong Hwan Che, Woo-Chan Son, Byeong Cheol Kang, Mi-Kyung Kim, Jae-Hak Park, and Yun Soon Kim
- Subjects
Male ,Urinalysis ,Pharmacology ,Kidney ,Toxicology ,medicine.disease_cause ,Median lethal dose ,Ames test ,Rats, Sprague-Dawley ,Biological Factors ,Republic of Korea ,medicine ,Animals ,Carcinogen ,Dose-Response Relationship, Drug ,medicine.diagnostic_test ,Mutagenicity Tests ,Chemistry ,Body Weight ,Toxicity Tests, Subchronic ,Organ Size ,General Medicine ,Rats ,Karyomegaly ,medicine.anatomical_structure ,Toxicity ,Female ,Medicine, Traditional ,Paecilomyces ,Genotoxicity ,Mutagens - Abstract
Paecilomyces tenuipes is entomogenous fungus that is called snow-flake Dongchunghacho in Korea. Although it is widely used in traditional medicines, its safety has not yet been comprehensively investigated. Therefore, the aim of this study was to evaluate the genotoxicity, acute and subchronic toxicity of P. tenuipes . The acute oral LD 50 of P. tenuipes extract in rats was estimated to be greater than 2000 mg/kg of body weight. In the subchronic study, the oral treatment of rats with 500, 1000 or 2000 mg/kg P. tenuipes extract daily for 13 weeks did not induce any dose-related changes (body weight, food consumption, clinical observation, urinalysis, hematology, clinical chemistry and organ weight). In contrast, histopathological observation revealed that P. tenuipes extract induced karyomegaly in outer medulla of kidney in all treated rats. Importantly, P. tenuipes extract exerted the mutagenic potential in Ames assay. Since karyomegalic alterations have been known to be associated with carcinogenicity, our finding on the mutagenicity of P. tenuipes extract supports the possibility on the potential involvement of P. tenuipes in carcinogenicity at least partially. In conclusion, the subchronic oral exposure of P. tenuipes may induce kidney abnormality at the concentration higher than 500 mg/kg body weight, although further studies using other animal models are needed to identify the toxicity of P. tenuipes .
- Published
- 2014
12. Preclinical study of safety of Dendropanax morbifera Leveille leaf extract: General and genetic toxicology
- Author
-
Eun Young Cho, Eun Jin Choi, Jeong Hwan Che, Jung Hee Yoon, Ji Ran You, Byeong Cheol Kang, Seung Hyun Kim, Yun Soon Kim, Hyoung Chin Kim, Euna Kwon, Ja June Jang, Jun Won Yun, and Jin-Sung Park
- Subjects
Male ,Urinalysis ,medicine.disease_cause ,Chromosome aberration ,Cell Line ,Rats, Sprague-Dawley ,Magnoliopsida ,Mice ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Oral administration ,Cricetinae ,Drug Discovery ,Animals ,Medicine ,Adverse effect ,030304 developmental biology ,Chromosome Aberrations ,Pharmacology ,Mice, Inbred ICR ,0303 health sciences ,Traditional medicine ,medicine.diagnostic_test ,Mutagenicity Tests ,Plant Extracts ,business.industry ,Fibroblasts ,Rats ,Plant Leaves ,030220 oncology & carcinogenesis ,Micronucleus test ,Toxicity ,Female ,business ,Genotoxicity - Abstract
Ethnopharmacology relevance Dendropanax morbifera Leveille (DM) has been used in traditional medicines for infectious and skin diseases, and dysmenorrhea. It exhibits a diverse therapeutic potential including anti-cancer, anti-thrombotic, anti-diabetic, anti-oxidant, and anti-inflammatory activities. Aim of the study Despite promising health benefits of DM, knowledge of its potential adverse effects is very limited. The current study focused on the investigation of subchronic toxicity and genotoxicity of extract obtained from DM according to the test guidelines published by the Organization for Economic Cooperation and Development. Materials and methods We conducted a toxicological evaluation of DM extracts using 14-day repeated-dose toxicity study and 13-week repeated-dose toxicity study in Sprague-Dawley rats administered orally at doses of 500, 1000, or 2000 mg/kg/day. The clastogenicity of DM extract was also evaluated by in vitro chromosome aberration assay and in vivo micronucleus assay. Results Assessment of subchronic toxicity of DM extract by oral administration in rats revealed unremarkable treatment-related findings with respect to food/water consumption, body weight, mortality, urinalysis, hematology, serum biochemistry, necropsy, organ weight and histopathology at doses of 500, 1000, and 2000 mg/kg. Accordingly, the level of no-observed-adverse-effect for DM extract in 13-week subchronic toxicity study was considered to be 2000 mg/kg/day in rats. The data observed from in vitro chromosome aberration assay and in vivo micronucleus assay exclude any clastogenicity of DM extract. Conclusion The results suggest that the oral consumption of DM extract has no adverse effects in humans and represents a safe traditional medicine.
- Published
- 2019
13. CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis, and apoptosis
- Author
-
Seong Ho Yoo, Ali Keshavarzian, Atrayee Banerjee, Frank J. Gonzalez, Sehwan Jang, Jun Won Yun, Byoung Joon Song, and Mohamed A. Abdelmegeed
- Subjects
Male ,medicine.medical_specialty ,Alcoholic liver disease ,SOD2 ,Apoptosis ,Biology ,medicine.disease_cause ,Biochemistry ,Article ,Binge Drinking ,Mice ,Enterobacteriaceae ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,ALDH2 ,Mice, Knockout ,Ethanol ,Fatty liver ,Cytochrome P-450 CYP2E1 ,CYP2E1 ,Lipid Metabolism ,medicine.disease ,Endotoxemia ,Endotoxins ,Fatty Liver ,Intestines ,Oxidative Stress ,Endocrinology ,Liver ,Cytokines ,Female ,Steatosis ,Steatohepatitis ,Oxidative stress ,Signal Transduction - Abstract
Ethanol-inducible cytochrome P450 2E1 (CYP2E1) contributes to increased oxidative stress and steatosis in chronic alcohol-exposure models. However, its role in binge ethanol-induced gut leakiness and hepatic injury is unclear. This study was aimed to investigate the role of CYP2E1 in binge alcohol-induced gut leakiness and the mechanisms of steatohepatitis. Female wild-type (WT) and Cyp2e1-null mice were treated with three doses of binge ethanol (WT-EtOH or Cyp2e1-null-EtOH) (6 g/kg oral gavage at 12-h intervals) or dextrose (negative control). Intestinal histology of only WT-EtOH exhibited epithelial alteration and blebbing of lamina propria while liver histology obtained at 6 h after the last ethanol dose showed elevated steatosis with scattered inflammatory foci. These were accompanied by increased levels of serum endotoxin, hepatic enterobacteria and triglycerides. All these changes including the intestinal histology and hepatic apoptosis, determined by TUNEL assay, were significantly reversed when WT-EtOH mice were treated with the specific inhibitor of CYP2E1 chlormethiazole and the antioxidant N-acetyl-cysteine, both of which suppressed the oxidative markers including intestinal CYP2E1. WT-EtOH also exhibited elevated amounts of serum TNF-α, hepatic cytokines, CYP2E1 and lipid peroxidation with decreased levels of mitochondrial superoxide dismutase and suppressed aldehyde dehydrogenase 2 activity. Increased hepatocyte apoptosis with elevated levels of pro-apoptotic proteins and decreased levels of active (phosphorylated) p-AKT, p-AMPK and peroxisome proliferator-activated receptor-alpha (PPAR-α), all of which are involved in fat metabolism and inflammation, were observed in WT-EtOH. These changes were significantly attenuated in the corresponding Cyp2e1-null-EtOH mice. These data indicate that both intestinal and hepatic CYP2E1 induced by binge alcohol seem critical in the binge alcohol-mediated increased nitroxidative stress, gut leakage, endotoxemia, and altered fat metabolism, and inflammation, contributing to hepatic apoptosis and steatohepatitis.
- Published
- 2013
14. Antipruritic Effects of TRPV1 Antagonist in Murine Atopic Dermatitis and Itching Models
- Author
-
Kyung Min Lim, Young-Ho Park, Won Hee Jang, Il-Hong Bae, Jun Won Yun, Hyun Ju Koh, and Seo Jung A
- Subjects
Male ,medicine.medical_specialty ,Pyridines ,TRPV1 ,TRPV Cation Channels ,Dermatology ,Substance P ,Biochemistry ,Dermatitis, Atopic ,Mice ,Th2 Cells ,Animals ,p-Methoxy-N-methylphenethylamine ,Medicine ,Molecular Biology ,Antipruritic ,Acrylamides ,Dermatophagoides farinae ,business.industry ,Antagonist ,Antipruritics ,Cell Biology ,Atopic dermatitis ,medicine.disease ,Disease Models, Animal ,Itching ,medicine.symptom ,business ,medicine.drug - Published
- 2011
15. Immunohistological comparison of cutaneous pathology of three representative murine atopic dermatitis models
- Author
-
Jun Won Yun, Minsoo Noh, Young Ho Park, Kyung Min Lim, Seo Jung A, Il-Hong Bae, Kyoung Mi Jung, and Kwang-Mi Kim
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,Dermatology ,Atopic dermatitis ,medicine.disease ,Biochemistry ,medicine ,Loricrin ,Immunohistochemistry ,business ,Molecular Biology ,Filaggrin - Published
- 2010
16. Expression levels of pituitary tumor transforming 1 and glutathione-S-transferase theta 3 are associated with the individual susceptibility to d-galactosamine-induced hepatotoxicity
- Author
-
Il-Hong Bae, Kyung-Sun Kang, Young Ho Park, Jun Won Yun, Jin Ho Chung, Kyung Min Lim, and Chae Wook Kim
- Subjects
Male ,medicine.medical_specialty ,Microarray ,Galactosamine ,Biology ,Pharmacology ,Toxicology ,Rats, Sprague-Dawley ,Liver Function Tests ,Internal medicine ,Genetic variation ,Gene expression ,medicine ,Animals ,Glutathione Transferase ,Oligonucleotide Array Sequence Analysis ,Liver injury ,medicine.diagnostic_test ,Reverse Transcriptase Polymerase Chain Reaction ,Microarray analysis techniques ,medicine.disease ,Neoplasm Proteins ,Rats ,Securin ,Endocrinology ,Glutathione S-transferase ,Liver ,biology.protein ,RNA ,Chemical and Drug Induced Liver Injury ,Liver function tests ,Toxicogenomics - Abstract
Although drug-induced liver injury (DILI) is frequently observed, individual variation in the susceptibility to DILI is hard to predict. Intrinsic genetic variation is considered a key element for this variation but little is known about the identity of the genes associated with DILI. In this study, pre-biopsy method was applied to uncover the key genes for D-galactosamine (GalN)-induced liver injury and a cause and effect study was conducted to elucidate the correlation between the expression of uncovered genes and GalN-induced hepatotoxicity. To identify the genes determining the susceptibility to GalN-induced hepatotoxicity, we compared the innate gene expression profiles in the liver tissue pre-biopsied before GalN treatment of the SD rats susceptible and resistant to GalN-induced hepatotoxicity, using microarray. Eight genes including Pttg1, Ifit1 and Gstt3 were lower or higher in the susceptible animals than the resistant and RT-PCR analysis confirmed it. To determine if these genes are associated with the susceptibility to GalN-induced hepatotoxicity indeed, expression levels were measured using real-time PCR in a new set of animals and the correlation with GalN-induced hepatotoxicity were analyzed. Notably, the expression of Pttg1 was significantly correlated with the severity of GalN-induced hepatotoxicity (p
- Published
- 2010
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.