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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>
Hyunsu Kim,Kyung‑Wan Baek,고은지,Nguyen Thanh Luan,Yunjin Lim,Heyong Jin Roh,Nameun Kim,Do‑Hyung Kim,Ahran Kim,Yung Hyun Choi,Suhkmann Kim,Heui‑Soo Kim,Mee Sun Ock,차희재 한국유전학회 2020 Genes & Genomics Vol.42 No.7
Background Viral hemorrhagic septicemia (VHS) is a serious viral disease that infects the olive flounder in South Korea. The Korean aquaculture industry experienced an economic loss caused by the high infectivity and mortality. Objective This study aimed to evaluate the infection density of VHSV in various organs of the olive flounder including spleen, liver, kidney, stomach, esophagus, intestine, gill, muscle, heart, and brain. Olive flounders were collected from a local fish farm and injected subcutaneously with 106 PFU/fish. Methods Each 15 fish were sampled at 0, 3, and 7 days post challenge (dpc), respectively, to perform quantitative analysis of VHSV using SYBR-green based real-time PCR in various tissues including spleen, liver, head-kidney, body-kidney, muscle, esophagus, stomach, intestine, gill, and brain. Results Organs infected with VHSV were obtained after 3 and 7 days. Each organs were examined for viral infection using real-time PCR. The data obtained from this experiment revealed copy numbers higher than 10 copies per 100 ng cDNA in the spleen (15.26 ± 3.11 copies/100 ng of cDNA), muscle (11.24 ± 2.25 copies), and gill (14.23 ± 6.26 copies), but lower in liver, head-kidney, body-kidney, esophagus, brain and stomach. Conclusion The present study, together with previous data, demonstrated that the gill, spleen, and muscle are the major target organs of VHSV in olive flounder. Therefore, central monitoring of spleen, gill and muscle should be considered and might be necessary if anti-VHSV treatment is to be successful in infected olive flounder.
Kim, Ji Won,Ryu, Sung Ha,Kim, Siwon,Lee, Hae Won,Lim, Mi-sun,Seong, Sook Jin,Kim, Suhkmann,Yoon, Young-Ran,Kim, Kyu-Bong American Chemical Society 2013 ANALYTICAL CHEMISTRY - Vol.85 No.23
<P>Drug-induced liver injury (DILI) is currently an increasingly relevant health issue. However, available biomarkers do not reliably detect or quantify DILI risk. Therefore, the purpose of this study was to comparatively evaluate plasma and urinary biomarkers obtained from humans treated with acetaminophen (APAP) using a metabolomics approach and a proton nuclear magnetic resonance (NMR) platform. APAP (3 g/day, two 500 mg tablets every 8 h) was administered to 20 healthy Korean males (age, 20–29 years) for 7 days. Urine was collected daily before and during dosing and 6 days after the final dose. NMR spectra of these urine samples were analyzed using principal component analysis (PCA) and partial least-squares-discrimination analysis. Although the activities of aspartate aminotransferase and lactate dehydrogenase were significantly increased 7 days post-APAP treatment, serum biochemical parameters of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, γ-glutamyl transpeptidase, and lactate dehydrogenase were within normal range of hepatic function. However, urine and plasma <SUP>1</SUP>H NMR spectroscopy revealed different clustering between predosing and after APAP treatment for global metabolomic profiling through PCA. Urinary endogenous metabolites of trimethylamine-N-oxide, citrate, 3-chlorotyrosine, phenylalanine, glycine, hippurate, and glutarate as well as plasma endogenous metabolites such as lactate, glucose, 3-hydroxyisovalerate, isoleucine, acetylglycine, acetone, acetate, glutamine, ethanol, and isobutyrate responded significantly to APAP dosing in humans. Urinary and plasma endogenous metabolites were more sensitive than serum biochemical parameters. These results might be applied to predict or screen potential hepatotoxicity caused by other drugs using urinary and plasma <SUP>1</SUP>H NMR analyses.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancham/2013/ancham.2013.85.issue-23/ac402390q/production/images/medium/ac-2013-02390q_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ac402390q'>ACS Electronic Supporting Info</A></P>
Metabolomics approach to serum biomarker for loperamide-induced constipation in SD rats
Ji-Eun Kim,Young-Ju Lee,Moon-Hwa Kwak,Go Jun,Eun-Kyoung Koh,Sung-Hwa Song,Ji-Eun Seong,Ji Won Kim,Kyu-Bong Kim,Suhkmann Kim,Dae-Youn Hwang 한국실험동물학회 2014 Laboratory Animal Research Vol.30 No.1
Loperamide has long been known as an opioid-receptor agonist useful as a drug for treatment of diarrhea resulting from gastroenteritis or inflammatory bowel disease as well as to induce constipation. To determine and characterize putative biomarkers that can predict constipation induced by loperamide treatment, alteration of endogenous metabolites was measured in the serum of Sprague Dawley (SD) rats treated with loperamide for 3 days using ¹H nuclear magnetic resonance (¹H NMR) spectral data. The amounts and weights of stool and urine excretion were significantly lower in the loperamide-treated group than the Notreated group, while the thickness of the villus, crypt layer, and muscle layer was decreased in the transverse colon of the same group. The concentrations of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatinine (Cr) were also slightly changed in the loperamide-treated group, although most of the serum components were maintained at a constant level. Furthermore, pattern recognition of endogenous metabolites showed completely separate clustering of the serum analysis parameters between the Notreated group and loperamide-treated group. Among 35 endogenous metabolites, four amino acids (alanine, glutamate, glutamine and glycine) and six endogenous metabolites (acetate, glucose, glycerol, lactate, succinate and taurine) were dramatically decreased in loperamide-treated SD rats. These results provide the first data pertaining to metabolic changes in SD rats with loperamide-induced constipation. Additionally, these findings correlate the changes in 10 metabolites with constipation.
( Ji Won Kim ),( Sung Ha Ryu ),( Siwon Kim ),( Hae Won Lee ),( Mi Sun Lim ),( Sook Jin Seong ),( Suhkmann Kim ),( Young Ran Yoon ),( Kyu Bong Kim ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0
Drug-induced liver injury (DILI) is currently an increasingly relevant health issue. However, available biomarkers do not reliably detect or quantify DILI risk. Therefore, the purpose of this study was to comparatively evaluate plasma and urinary biomarkers obtained from humans treated with acetaminophen (APAP) using a metabolomics approach and a proton nuclear magnetic resonance (NMR) platform. APAP (3 g/day, two 500 mg tablets every 8 h) was administered to 20 healthy Korean males (age, 20-29 years) for 7 days. Urine was collected daily before and during dosing and 6 days after the final dose. NMR spectra of these urine samples were analyzed using principal component analysis (PCA) and partial least-squares-discrimination analysis. Although the activities of aspartate aminotransferase and lactate dehydrogenase were significantly increased 7 days post-APAP treatment, serum biochemical parameters of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, γ-glutamyl transpeptidase, and lactate dehydrogenase were within normal range of hepatic function. However, urine and plasma (1)H NMR spectroscopy revealed different clustering between predosing and after APAP treatment for global metabolomic profiling through PCA. Urinary endogenous metabolites of trimethylamine-N-oxide, citrate, 3-chlorotyrosine, phenylalanine, glycine, hippurate, and glutarate as well as plasma endogenous metabolites such as lactate, glucose, 3-hydroxyisovalerate, isoleucine, acetylglycine, acetone, acetate, glutamine, ethanol, and isobutyrate responded significantly to APAP dosing in humans. Urinary and plasma endogenous metabolites were more sensitive than serum biochemical parameters. These results might be applied to predict or screen potential hepatotoxicity caused by other drugs using urinary and plasma (1)H NMR analyses.
Ko Eun-Ji,Kim Hyunsu,Lee A-Reum,Jeon Kyung‑Yoon,Kim Ahran,Kim Do‑Hyung,Park Chan-Il,Choi Yung Hyun,Kim Suhkmann,Kim Heui-Soo,옥미선,차희재 한국유전학회 2021 Genes & Genomics Vol.43 No.11
Background Rock bream iridovirus (RBIV) is one of the most dangerous pathogens that causes the highest mortality in the aquaculture of rock bream (Oplegnathus fasciatus). Even though RBIV infection leads to huge economic loss, proteome studies on RBIV-infected rock bream have not been conducted to provide information about the diferential protein expression pattern by the host protection system. Objective The purpose of this study was to investigate the protein expression patterns in spleens of rock bream olive after infection by RBIV or mixed infection by RBIV and bacteria. Methods Depending on the infection intensity and sampling time point, fsh were divided into fve groups: uninfected healthy fsh at week 0 as the control (0C), heavily infected fsh at week 0 (0H), heavily mixed RBIV and bacterial infected fsh at week 0 (0MH), uninfected healthy fsh at week 3 (3C), and lightly infected fsh at week 3 (3L). Proteins were extracted from the spleens of infected rock bream. We used 2-DE analysis with LC–MS/MS to investigate proteome changes in infected rock bream. Results The results of the LC–MS/MS analyses showed diferent protein expression profles after infection. Proteins related to oxygen transport and energy generation, such as hemoglobin, beta-globin, and ATP synthase, were mostly expressed in the infected spleen. Whereas proteins involved in structure and cell movement, such as tubulin, myosin, actin binding proteins, and intermediate flament proteins, were down-regulated in the infected spleens. The protein expression profles between infection by RBIV and mixed infection by RBIV and bacteria showed similar patterns. Conclusions Our results indicated that infection by RBIV or mixed infection by RBIV and bacteria triggered energy generation and oxygen-transport, but cell migration and constructional changes in the spleen were extremely decreased.