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>

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>

부산지역 수돗물과 지하수의 중금속 농도

김준연,손지언,김형수,김두희,원미숙,김인식,이혜령 동아대학교 산업의학연구소 2000 산업의학연구소 논총 Vol.- No.5

This study investigated mean airborne CO concention of 15 workplaces, suspected of CO exposure and conducted self-reported questionnaire completion and indirect COHb concentration measure using Micro II Smokerlyzer to healthy 702 adult subjects from 1999 May to 1999 September in order to find a relation of CO exposure and occupational factors, socioeconomic factors, and health related behaviors and confirm the related conditions in the screening test for CO exposure. The results of this study were summarized as follows : 1. In the CO exposed and non exposed group, COHb concentrations of the smokers were 2.55±0.96% and 2.21±0.97% and that got a statistically significant difference, There were not statistically significant differences in the age and total smoking index. Passed times after the last smoking, Working time/day, and working duration were statistically significant difference (p〈0.05). 2. In the CO exposed and non exposed group, COHb concentrations of non-smoking group were 0.94±0.35% and 0.68±0.47% and that got a statistically significant difference. There were not statistically significant differences in the age and working duration but Working time/day was a statistically significant difference(p〈0.05). 3. In the CO exposed group, r-square of multiple regression of the smokers was 38.5 % and passed time after the last smoking, working time/day, and job category were statistically significant differences (p〈0.05). And r-square in the CO non-exposed group was 38.3 % and age, passed time after the last smoking, and total smoking index were statistically significant difference. 4. In the CO exposed group, r-square of multiple repression of the non-smokers was 66.3% and job category and airborne CO concentration were statistically significant differences(p〈0.05). But r-square of non-smokers in the CO non-exposed group was 1.0% and there was not a statistically significant difference(p〈0.05). 5. In the smokers of CO exposed and non exposed groups, relation of COHb concentration and passed time after the last smoking was expressed as exponential function, Y = 2.9182e-0.0083x and r-square of this function was 37.4%. Therefore it was more than 150 minutes that passed time after the last smoking was when COHb concentrations were measured as less than 1%. In conclusion, variable, that was statistically significant to COHb concentraion in the both CO exposed and non-exposed smokers, was a passed time after the last smoking. We suggest that you have to restrict the smoking of smokers at least 150 minutes in the exposed and non exposed group before COHb concentration measure in order to exclude smoking effects

Assessment of In Vitro Assay System for Thyroid HormoneDisruptors Using Rat Pituitary GH3 Cells

Hee Jin Kim1,Hae Young Park1,Jeonga Kim1,Il Hyun Kang2,Tae Sung Kim2,Soon Young Han2,Tae Seok Kang2,Kui Lea Park2,Hyung Sik Kim1 한국독성학회 2006 Toxicological Research Vol.22 No.4

The development of in vitro assays has been recommended to screening and test-ing the potential endocrine disruptors (EDs). These assay systems focus only on identifying thethe thyroid hormone (TH) disruptors. The aim of this study was to evaluate a test system to detectTH disruptors using rat pituitary tumor GH3 cells. The test system is based on the TH-dependentincrease in growth rate. As expected, L-3,5,3-triiodothyronine (T3) markedly induced a morphologicalchange in GH 3 cells from flattened fibroblastic types to rounded or spindle-shaped types. T3 stimu-lated GH3 cell growth in a dose-dependent manner with the maximum growth-stimulating effect9 M. In addition, T3 increased the release of growth hor-mone and prolactin into the medium of the GH3 cells culture. Using this assay system, the TH-dis-rupting activities of bisphenol A (BPA) and its related compounds were examined. BPA,dimethylbisphenol A (DMBPA), and TCI-EP significantly enhanced the growth of GH3 cells in therange of 1 × 10-5M to 1 × 10-6M concentrations. In conclusion, this in vitro assay system might bestandardization before it can be used as a broad-based screening tool.

딤플을 적용한 평판에 대한 항력 감소 연구

백부근(Bu-Geun Paik),편영식(Young-Sik Pyun),김준형(Jun-Hyung Kim),김경열(Kyung-Youl Kim),김기섭(Kim1 ?Ki-Sup),정철민(Chul-Min Jung),김찬기(Chan-Ki Kim) 대한조선학회 2012 大韓造船學會 論文集 Vol.49 No.4

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.

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.

한의진단명과 진단요건의 표준화 연구 III : 3차년도 연구결과 보고

최선미,양기상,최승훈,박경모,박종현,심범상,김성우,노석선,이인선,정진홍,이진용,김달래,임형호,김윤범,박성식,송태원,김종우,이승기,최윤정,신순식 한국한의학연구원 1997 한국한의학연구원논문집 Vol.3 No.1

The diagnostic requirements were suggested and explained regarding the systems of differentiation of symptoms and signs in the third year study of standardization and unification of the terms and conditions used for diagnosis in oriental medicine. The systems were as follows : - analyzing and differentiating of epidemic febrile disease - analyzing and differentiating in accordance with the Sasang constitution medicine based on four-type recognition - differentiation of disease according to pathological changes of Chong and Ren channels - standards for diagnosis of women's disease - standards for diagnosis of children's disease - standards for diagnosis of motor and sensor disturbance (-muscle. born, joint, etc.) - standards for diagnosis of neuropsychiatric disease - standards for diagnosis of five sense organ disease - standards for diagnosis of external disease The indivisual diagnosis pattern was arranged by the diagnostic requirements in the following order : another name, notion of diagnosis pattern, index of differentiation of symptoms and signs, the main point of diagnosis, analysis of diagnosis pattern, discrimination of diagnosis pattern, prognosis, a way of curing a disease, prescription, herbs in common use, disease appearing the diagnosis pattern, documents. The standards for diagnosis of each disease was arranged by the diagnostic requirements in the following order : another name, notion of disease, the main point of diagnosis, analyzing and differentiating of disease, analysis of disease, discrimination of disease, prognosis, a way of curing and prescription of disease, disease in western medicine appearing the disease in oriental medicine, documents.

Original Article : 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 Ki 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

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.

DC방전에 대한 전류 및 전압 조건에서 1차원 전산모사

김희정,김형용,권득철,윤남식 충북대학교 컴퓨터정보통신 연구소 2006 컴퓨터정보통신연구 Vol.14 No.1

여러 그룹들의 연구 결과로서 DC 방전 전산모사를 위한 여러 가지 수치해석적 방법들이 보고되어 왔다. 대부분의 방법들은 전극에 전압을 경계 조건으로 가정하고 전류를 구하는 방법인데, 때로는 전류값을 조건으로 주고 전극의 전압이 결정되는 방법이 필요한 경우도 있다. 본 연구에서는 전류값이 조건으로 주어진 경우에 전극의 전압이 결정되는 방법을 적용했으며, 1차원 전산모사를 통해 두 가지 방법에 의한 결과를 비교하였다. Various numerical simulation algorithms for simulating DC discharge were reported from many research groups. Most of reported methods uses terminal electrode voltage as a boundary condition to obtain current density. However, in some case, we need to obtain terminal voltage from boundary condition of current. In this paper, the method which obtain voltage under current condition is applied, and we compared the results of two methods through one-dimensional simulations.