Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury

Kim, Kyeong Seok,Yang, Hun Yong,Song, Hosup,Kang, Ye Rim,Kwon, JiHoon,An, JiHye,Son, Ji Yeon,Kwack, Seung Jun,Kim, Young-Mi,Bae, Ok-Nam,Ahn, Mee-Young,Lee, Jaewon,Yoon, Sungpil,Lee, Byung μ,Kim, Hyung TAYLOR & FRANCIS 2017 Journal of Toxicology and Environmental Health Vol.80 No.9

<P>Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.</P>

Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury

Won, A Jin,Kim, Siwon,Kim, Yoon Gyoon,Kim, Kyu-Bong,Choi, Wahn Soo,Kacew, Sam,Kim, Kyeong Seok,Jung, Jee H.,Lee, Byung Mu,Kim, Suhkmann,Kim, Hyung Sik The Royal Society of Chemistry 2016 Molecular bioSystems Vol.12 No.1

<P>The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg(-1), i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-alpha (GST-alpha), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.</P>

위에 발생한 유암종 (Carcinoid Tumor) : 1예 보고

김남재,김진희,이경태,서광식,정현용,이승민,김석현,이병석,이헌영 대한소화기내시경학회 1999 Clinical Endoscopy Vol.19 No.3

A carcinoid tumor of the stomach is uncommon, has no clinical symptoms, and is regarded as a benign. It is also incidentally found in most cases. 48-year-old woman with gastric carcinoid tumor was admitted. She had suffered from a anorexia and a dry mouth for 4-months. A gastroscopy revealed a polypoid mass on the greater curvature of the mid-body of the stomach which was subsequently thought to be an adenocarcinoma. An endoscopic mucosectomy revealed however, that it was a carcinoid tumor. A case of carcinoid tumor of the stomach is here by presented with a brief literature review.

Curcumin ameliorates cadmium-induced nephrotoxicity in Sprague-Dawley rats

Kim, Kyeong Seok,Lim, Hyun-Jung,Lim, Jong Seung,Son, Ji Yeon,Lee, Jaewon,Lee, Byung Mu,Chang, Seung-Cheol,Kim, Hyung Sik Elsevier 2018 Food and chemical toxicology Vol.114 No.-

<P><B>Abstract</B></P> <P>Chronic exposure to cadmium (Cd) causes remarkable damage to the kidneys, a target organ of accumulated Cd after oral administration. The aim of the present study was to investigate the protective effect of curcumin against Cd-induced nephrotoxicity. Sprague–Dawley male rats were divided into the following four treatment groups: control, curcumin (50 mg/kg, oral), CdCl<SUB>2</SUB>, (25 mg/kg, oral), and pre-treatment with curcumin (50 mg/kg) 1 h prior to the administration of CdCl<SUB>2</SUB> (25 mg/kg, oral) for 7 days. At 24 h after the final treatment, the animals were killed, and the biomarkers associated with nephrotoxicity were measured. Our data indicated that blood urea nitrogen (BUN) and serum creatinine (sCr) levels were significantly reduced by curcumin pre-treatment in CdCl<SUB>2</SUB>-treated animals. Histopathological studies showed hydropic swelling and hypertrophy of the proximal tubular cells in the renal cortex after Cd treatment. Pretreatment with curcumin ameliorated the histological alterations induced by Cd. The urinary excretion of kidney injury molecule-1 (Kim-1), osteopontin (OPN), tissue inhibitor of metalloproteinases 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL), and netrin-1 significantly reduced by curcumin treatment compared to that in the CdCl<SUB>2</SUB>-treated group. The administration of curcumin provided a significant protective effect against Cd-induced nephrotoxicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Curcumin protects against cadmium-induced renal injury. </LI> <LI> Curcumin reduces urinary excretion of AKI biomarkers. </LI> <LI> Curcumin protects against cadmium-induced apoptosis in the kidney. </LI> </UL> </P>

독성물질의 세포사 기전 및 세포사 유발물질의 검색법 개발에 관한 연구(Ⅰ) : 독성물질로 인한 파킨슨병 모델에서의 세포사 기전 연구 Study on the cell-death mechanisms of toxin-induced parkinsonism

강태석,김종민,서경원,김영옥,김준규,오재호,이윤동,김규봉,오정자,송연정,임종준,전범석,문전옥,최광식 식품의약품안전청 2000 식품의약품안전청 연보 Vol.4 No.-

MPTP 독성물질이 도파민성 신경세포에 선택적으로 작용하여 산화성 손상에 의한 신경세포사를 일으키는 것을 이용하여 파킨슨병의 동물모델을 만들고, 이를 통해서 아폼토시스를 비롯한 포사의 기전에 대한 연구 및 너코틴의 신경세포 보호효과 여부를 판정하는 실험을 병행하고자 하였다. 파킨슨꾐의 동물모델을 MPTf 독성 물질을 이용하여 확립하였으며, MPTP(30mgag, i.p.)를 투여한 후 1, 2,3, 4, 5일째 흑질 조직을 채춰하여 tarm로 박걸하여 tyrosine hydroxylase 면역조직화학염색을 수행하여 cell countif우한 결과, control은 57.635ce11s, 1일째 친.OfDells,2일째 57.9±6cells,3일릴 없.3±죠ells, 4일째 49.0츠3cells, 5일째 39.4±Scells료 4, 3일째 뚜렷한 신경세포 수의 감소를 보였다. 신경세포사 기전 규명을 위한 아폼토시스 분걱에서는 벼PTP 투여 후 1, 2, 3, 4, 5일째 조직을 채취하여 Hoechst staining, TUNEL staining을 수곡하였는데 양성 반응을 보인 신경세포는 관찰되지 않아. 아폼토시스로 인한 세포사가 관찰되지 않았다. bIPTP 파킨슨병 동물모델에서 nicotine 보호효과 탐색에 관한 실험은 nicat푸e 0.2mgAg을 5일 퐁안 투여 후 리『fP(30mgag)를 CS7Bt/6 마은스에 복강 내주사로 nicotine과 병용 투여한 후 1, 2, 3, 4, 5일째 뇌를 적출하땄다. 신경세포사가 뚜렷이 관찰되기 시작하는 4, 5일째의 신경세포 수의 감소 정도를 20. 30% 정도 약화시키는 경향을 보였으나, nicotine 보호효과에 대한 추가 실헝이 현재 수행 중에 있다. The cause of Parkinson's disease (PD) is largely unknown. However, free radical toxicit? may plaf a role ip. the degeneration of substantia nigra, which is the Hajorfocus of pathological damages in PD. Recently, a neuroprotective effect of nicotine in PD has been suggested. Therefore, the mechanism of neurodegenerafion and protective potential o( nicotine in PD were investigated in the experimental modeB of Pll using a neurotoxin, C57BL/6mice were administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg,j.p.). The degree of neurodegenerafion was determined by immunohistochemical stainiHB oftyrosine hydroxylase (TH). TH-positive cells on nigral sections were found 56.0 ±4, 57.9 ±6,52.315ce11s, 49.0±3cells, and 39,4±Scells at days 1, 2, 3, 4, 5, respectively (controls : 57.6±Scells). Hoechst and TUNEL staining showed no evidence of apoptosis. The exandnation on themice co-adrunistered with nicotine(0.2mgAg) and MPTP(30mgag) revealed a tendency ofnicotine protective effects. At days 4 and 5, the degree of TH-positive cells was decreased by20-30%, In corclusiffn, the role of apoptosis was not evidenced in this MPTP modeB of PB.The possible proteccon by nicotine should be elucidated with further studies.

Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

Ji Yeon Son,Yoon Jong Kang,Kyeong Seok Kim,Tae Hyung Kim,Sung Kwang Lim,Hyun Jung Lim,Tae Cheon Jeong,Dal Woong Choi,Kyu Hyuck Chung,Byung Mu Lee,Hyung Sik Kim 한국독성학회 2014 Toxicological Research Vol.30 No.2

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

Son, Ji Yeon,Kang, Yoon Jong,Kim, Kyeong Seok,Kim, Tae Hyung,Lim, Sung Kwang,Lim, Hyun Jung,Jeong, Tae Cheon,Choi, Dal Woong,Chung, Kyu Hyuck,Lee, Byung Mu,Kim, Hyung Sik Korean Society of ToxicologyKorea Environmental Mu 2014 Toxicological Research Vol.30 No.2

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

오픈프라이스 제도에 대한 소비자인식도 및 만족도

김인석, 서경원, 유현정 충북대학교 생활과학연구소 2013 생활과학연구논총 Vol.17 No.2

The purpose of this study was to analyze consumers' awareness and satisfaction of open price system. Questionnaire survey was conducted from 3 September to 14 September 2011. We have surveyed 200 consumers who were living in Cheongju area. Major findings are as follows. First, consumers were not aware about open price system very well. The mean of the objectives and expected effects of open price system was 2.38. It means that many consumers when it comes to the open price system does not have the proper recognition was considered. Second, there was not big changes for consumers' information search behavior after execution the open price system. Third, consumers' satisfaction mean(m=2.32) of open price system was lower than dissatisfaction mean(m=3.40) of that. The main reason of dissatisfaction due to inconsistent pricing confusion was investigated. Fourth, there were statistic differences in open price system awareness and consumer behavior by consumers' socio-economics characteristics such as age, education, income, occupation, etc. Finally, consumers' satisfaction of open price system was influence by information search cost, product or brand image. On the other hand, consumers' dissatisfaction was only influence by open price system awareness.

도파민/세로토닌 길항성 비정형 항정신병약물로 치료 중인 정신분열병 환자에서 체중 증가의 관련 요인

김신겸,장원석,최경숙,박동연,한우상,이동수,홍경수 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.3

석청(Mad-honey) 복용 후 유발된 부정맥 1예

김용철,김남호,김승환,최준호,박은미,이상재,이은미,유남진,윤경호,오석규,정진원 圓光大學校 醫科學硏究所 2008 圓光醫科學 Vol.23 No.2

석청에 포함된 grayanotoxin에 의해 독성 작용이 나올 수 있으며, 이러한 독성 작용은 일반적으로 24시간 이내 저절로 회복된다. 최근에 본 저자들은 석청 복용 후 발생한 심실빈맥을 경험하였기에 보고하는 바이다. 49세 남자가 호흡곤란으로 내원하였으며, 내원당시 분당 40회 정도의 동성 서맥이 관찰되었고, 수액을 투여하던 중 심실 빈맥이 발생하였다. 항부정맥제를 투여 후 정상 동율동으로 전환되었으며, 특별한 이상 없이 4일 후 퇴원하였다. Mad-honey intoxication caused by the consumption of honey producted from the nectar of rhododendrons. The grayanotoxins cause the intoxication. The toxic effects of mad-honey poisoning are rarely fatal and generally last for no more than 24 hours. We experienced one case, a 49 years-old man who presented with dyspnea after ingestion of mad-honey. He showed marked sinus bradycardia with < 40 beats per minute on admission. The cardiac rhythm was changed to ventricular tachycardia immediately. These features resolved completely in 24 hours with continuous infusion of amiodarone(600 mg per day) and fluids. We report the case of intoxication of mad-honey as a presentation of fatal cardiac arrhythmia.