TY  - GEN
A1  - Lu, Yong-Ping
A1  - Reichetzeder, Christoph
A1  - Prehn, Cornelia
A1  - von Websky, Karoline
A1  - Slowinski, Torsten
A1  - Chen, You-Peng
A1  - Yin, Liang-Hong
A1  - Kleuser, Burkhard
A1  - Yang, Xue-Song
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Fetal serum metabolites are independently associated with Gestational diabetes mellitus
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Background/Aims: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32:1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM. (c) 2018 The Author(s) Published by S. Karger AG, Basel
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 637 
KW  - Gestational diabetes
KW  - metabolomics
KW  - phosphatidylcholine acyl-alkyl C 32:1
KW  - proline
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-424585
SN  - 1866-8372
IS  - 637
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Lu, Yong Ping
A1  - Reichetzeder, Christoph
A1  - Kalk, Philipp
A1  - Kleuser, Burkhard
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Maternal PCaaC38:6 is Associated With Preterm Birth - a Risk Factor for Early and Late Adverse Outcome of the Offspring
JF  - Journal of European public policy
N2  - Background/Aims: Preterm birth (PTB) and low birth weight (LBW) significantly influence mortality and morbidity of the offspring in early life and also have long-term consequences in later life. A better understanding of the molecular mechanisms of preterm birth could provide new insights regarding putative preventive strategies. Metabolomics provides a powerful analytic tool to readout complex interactions between genetics, environment and health and may serve to identify relevant biomarkers. In this study, the association between 163 targeted maternal blood metabolites and gestational age was investigated in order to find candidate biomarkers for PTB. Methods: Five hundred twenty-three women were included into this observational study. Maternal blood was obtained before delivery. The concentration of 163 maternal serum metabolites was measured by flow injection tandem mass spectrometry. To find putative biomarkers for preterm birth, a three-step analysis was designed: bivariate correlation analysis followed by multivariable regression analysis and a comparison of mean values among gestational age groups. Results: Bivariate correlation analysis showed that 2 acylcarnitines (C16:2, C2), 1 amino acids (xLeu), 8 diacyl-PCs (PCaaC36:4, PCaaC38:4, PCaaC38:5, PCaaC38:6, PCaaC40:4, PCaaC40:5, PCaaC40:6, PCaaC42:4), and 1 Acylalkyl-PCs (PCaeC40:5) were inversely correlated with gestational age. Multivariable regression analysis confounded for PTB history, maternal body mass index (BMI) before pregnancy, systolic blood pressure at the third trimester, and maternal body weight at the third trimester, showed that the diacyl-PC PCaaC38:6 was the only metabolite inversely correlated with gestational age. Conclusions: Maternal blood concentrations of PCaaC38:6 are independently associated with gestational age. (C) 2016 The Author(s) Published by S. Karger AG, Basel
KW  - Metabolomics
KW  - PCaaC38:6
KW  - Biomarker
KW  - Preterm birth
Y1  - 2016
U6  - https://doi.org/10.1159/000443428
SN  - 1420-4096
SN  - 1423-0143
VL  - 41
SP  - 250
EP  - 257
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Reichetzeder, Christoph
A1  - Putra, Sulistyo Emantoko Dwi
A1  - Li, Jian
A1  - Hocher, Berthold
T1  - Developmental Origins of Disease - Crisis Precipitates Change
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - The concept of developmental origins of diseases has gained a huge interest in recent years and is a constantly emerging scientific field. First observations hereof originated from epidemiological studies, linking impaired birth outcomes to adult chronic, noncommunicable disease. By now there is a considerable amount of both epidemiological and experimental evidence highlighting the impact of early life events on later life disease susceptibility. Albeit far from being completely understood, more recent studies managed to elucidate underlying mechanisms, with epigenetics having become almost synonymous with developmental programming. The aim of this review was to give a comprehensive overview of various aspects and mechanisms of developmental origins of diseases. Starting from initial research foci mainly centered on a nutritionally impaired intrauterine environment, more recent findings such as postnatal nutrition, preterm birth, paternal programming and putative interventional approaches are summarized. The review outlines general underlying mechanisms and particularly discusses mechanistic explanations for sexual dimorphism in developmental programming. Furthermore, novel hypotheses are presented emphasizing a non-mendelian impact of parental genes on the offspring's phenotype.
KW  - Nutrition
KW  - Thrifty phenotype
KW  - Developmental programming
KW  - Paternal, maternal, sex differences
KW  - Epigenetics
Y1  - 2016
U6  - https://doi.org/10.1159/000447801
SN  - 1015-8987
SN  - 1421-9778
VL  - 39
SP  - 919
EP  - 938
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Tsuprykov, Oleg
A1  - Ando, Ryotaro
A1  - Reichetzeder, Christoph
A1  - von Websky, Karoline
A1  - Antonenko, Viktoriia
A1  - Sharkovska, Yuliya
A1  - Chaykovska, Lyubov
A1  - Rahnenfuehrer, Jan
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Tammen, Harald
A1  - Alter, Markus L.
A1  - Klein, Thomas
A1  - Ueda, Seiji
A1  - Yamagishi, Sho-ichi
A1  - Okuda, Seiya
A1  - Hocher, Berthold
T1  - The dipeptidyl peptidase inhibitor linagliptin and the angiotensin II receptor blocker telmisartan show renal benefit by different pathways in rats with 5/6 nephrectomy
JF  - Kidney international : official journal of the International Society of Nephrology
N2  - Dipeptidyl peptidase (DPP)-4 inhibitors delay chronic kidney disease (CKD) progression in experimental diabetic nephropathy in a glucose-independent manner. Here we compared the effects of the DPP-4 inhibitor linagliptin versus telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. Animals were allocated to 1 of 4 groups: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus linagliptin; and 5/6 nephrectomy plus telmisartan. Interstitial fibrosis was significantly decreased by 48% with linagliptin but a non-significant 24% with telmisartan versus placebo. The urine albumin-to-creatinine ratio was significantly decreased by 66% with linagliptin and 92% with telmisartan versus placebo. Blood pressure was significantly lowered by telmisartan, but it was not affected by linagliptin. As shown by mass spectrometry, the number of altered peptide signals for linagliptin in plasma was 552 and 320 in the kidney. For telmisartan, there were 108 peptide changes in plasma and 363 in the kidney versus placebo. Linagliptin up-regulated peptides derived from collagen type I, apolipoprotein C1, and heterogeneous nuclear ribonucleoproteins A2/B1, a potential downstream target of atrial natriuretic peptide, whereas telmisartan up-regulated angiotensin II. A second study was conducted to confirm these findings in 5/6 nephrectomy wild-type and genetically deficient DPP-4 rats treated with linagliptin or placebo. Linagliptin therapy in wild-type rats was as effective as DPP-4 genetic deficiency in terms of albuminuria reduction. Thus, linagliptin showed comparable efficacy to telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. However, the underlying pathways seem to be different. Copyright (C) 2016, International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
KW  - albuminuria
KW  - angiotensin receptor blockers
KW  - chronic kidney disease
KW  - DPP-4 inhibition
KW  - proteinuria
KW  - proteomic analysis
Y1  - 2016
U6  - https://doi.org/10.1016/j.kint.2016.01.016
SN  - 0085-2538
SN  - 1523-1755
VL  - 89
SP  - 1049
EP  - 1061
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - JOUR
A1  - Tsuprykov, Oleg
A1  - Chaykovska, Lyubov
A1  - Kretschmer, Axel
A1  - Stasch, Johannes-Peter
A1  - Pfab, Thiemo
A1  - Krause-Relle, Katharina
A1  - Reichetzeder, Christoph
A1  - Kalk, Philipp
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Endothelin-1 overexpression improves renal function in eNOS knockout mice
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Background/Aims: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+), endothelial nitric oxide synthase knockout (eNOS-/-) and ET+/+eNOS-/- mice. Methods: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. Results: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpinel, TIMP1, Collal, CCL2) were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines, lysophosphatidylcholines and hexoses were descreased in eNOS-/- and were in the normal range in ET+/+eNOS-/- mice. Conclusion: eNOS-/- mice developed renal dysfunction, which was partially rescued by ET-1 overexpression in eNOS-/- mice. The metabolomics results suggest that ET-1 overexpression on top of eNOS knockout is associated with a functional recovery of mitochondria (rescue effect in 13-oxidation of fatty acids) and an increase in antioxidative properties (normalization of monounsaturated fatty acids levels). (C) 2015 The Author(s) Published by S. Karger AG, Basel
KW  - Chronic kidney disease
KW  - Endothelial nitric oxide synthase
KW  - Endothelin
KW  - Mice
KW  - Nitric oxide
Y1  - 2015
U6  - https://doi.org/10.1159/000438516
SN  - 1015-8987
SN  - 1421-9778
VL  - 37
IS  - 4
SP  - 1474
EP  - 1490
PB  - Karger
CY  - Basel
ER  - 
TY  - CHAP
A1  - Chen, Hong
A1  - Reichetzeder, Christoph
A1  - Föller, Michael
A1  - Slowinski, Torsten
A1  - Li, Jian
A1  - Chen, You-Peng
A1  - Lang, Florian
A1  - Hocher, Berthold
T1  - Maternal vitamin D deficiency and fetal programming
T2  - Acta physiologica : official journal of the Federation of European Physiological Societies
Y1  - 2015
SN  - 1748-1708
SN  - 1748-1716
VL  - 213
SP  - 155
EP  - 156
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - GEN
A1  - Hocher, Berthold
A1  - Oberthür, Dominik
A1  - Slowinski, Torsten
A1  - Querfeld, Uwe
A1  - Schaefer, Franz
A1  - Doyon, Anke
A1  - Tepel, Martin
A1  - Roth, Heinz J.
A1  - Grön, Hans J.
A1  - Reichetzeder, Christoph
A1  - Betzel, Christian
A1  - Armbruster, Franz Paul
T1  - Modeling of oxidized PTH (oxPTH) and non-oxidized PTH (n-oxPTH) receptor binding and relationship of oxidized to non-oxidized PTH in children with chronic renal failure, adult patients on hemodialysis and kidney transplant recipients
N2  - Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970(s) and 80(s). However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH. We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 343 
KW  - n-oxPTH
KW  - chronic renal failure
KW  - kidney transplantation
KW  - hemodialysis
KW  - oxidation
KW  - PTH
KW  - chronic renal failure in children
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-399980
ER  - 
TY  - GEN
A1  - Beaumont, Robin N.
A1  - Warrington, Nicole M.
A1  - Cavadino, Alana
A1  - Tyrrell, Jessica
A1  - Nodzenski, Michael
A1  - Horikoshi, Momoko
A1  - Geller, Frank
A1  - Myhre, Ronny
A1  - Richmond, Rebecca C.
A1  - Paternoster, Lavinia
A1  - Bradfield, Jonathan P.
A1  - Kreiner-Møller, Eskil
A1  - Huikari, Ville
A1  - Metrustry, Sarah
A1  - Lunetta, Kathryn L.
A1  - Painter, Jodie N.
A1  - Hottenga, Jouke-Jan
A1  - Allard, Catherine
A1  - Barton, Sheila J.
A1  - Espinosa, Ana
A1  - Marsh, Julie A.
A1  - Potter, Catherine
A1  - Zhang, Ge
A1  - Ang, Wei
A1  - Berry, Diane J.
A1  - Bouchard, Luigi
A1  - Das, Shikta
A1  - Hakonarson, Hakon
A1  - Heikkinen, Jani
A1  - Helgeland, Øyvind
A1  - Hocher, Berthold
A1  - Hofman, Albert
A1  - Inskip, Hazel M.
A1  - Jones, Samuel E.
A1  - Kogevinas, Manolis
A1  - Lind, Penelope A.
A1  - Marullo, Letizia
A1  - Medland, Sarah E.
A1  - Murray, Anna
A1  - Murray, Jeffrey C.
A1  - Njølstad, Pa ̊l R.
A1  - Nohr, Ellen A.
A1  - Reichetzeder, Christoph
A1  - Ring, Susan M.
A1  - Ruth, Katherine S.
A1  - Santa-Marina, Loreto
A1  - Scholtens, Denise M.
A1  - Sebert, Sylvain
A1  - Sengpiel, Verena
A1  - Tuke, Marcus A.
A1  - Vaudel, Marc
A1  - Weedon, Michael N.
A1  - Willemsen, Gonneke
A1  - Wood, Andrew R.
A1  - Yaghootkar, Hanieh
A1  - Muglia, Louis J.
A1  - Bartels, Meike
A1  - Relton, Caroline L.
A1  - Pennell, Craig E.
A1  - Chatzi, Leda
A1  - Estivill, Xavier
A1  - Holloway, John W.
A1  - Boomsma, Dorret I.
A1  - Montgomery, Grant W.
A1  - Murabito, Joanne M.
A1  - Spector, Tim D.
A1  - Power, Christine
A1  - Ja ̈rvelin, Marjo-Ritta
A1  - Bisgaard, Hans
A1  - Grant, Struan F.A.
A1  - Sørensen, Thorkild I.A.
A1  - Jaddoe, Vincent W.
A1  - Jacobsson, Bo
A1  - Melbye, Mads
A1  - McCarthy, Mark I.
A1  - Hattersley, Andrew T.
A1  - Hayes, M. Geoffrey
A1  - Frayling, Timothy M.
A1  - Hivert, Marie-France
A1  - Felix, Janine F.
A1  - Hyppo ̈nen, Elina
A1  - Lowe, William L. , Jr
A1  - Evans, David M.
A1  - Lawlor, Debbie A.
A1  - Feenstra, Bjarke
A1  - Freathy, Rachel M.
T1  - Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 Â 10 À8 . In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 628 
KW  - alleles
KW  - birth weight
KW  - fetus
KW  - genotype
KW  - mothers
KW  - single nucleotide polymorphism
KW  - genetics
KW  - duration of gestation
KW  - genome-wide association study
KW  - offspring
KW  - biobanks
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-423100
SN  - 1866-8372
IS  - 628
ER  - 
TY  - JOUR
A1  - Putra, Sulistyo E. Dwi
A1  - Reichetzeder, Christoph
A1  - Meixner, Martin
A1  - Liere, Karsten
A1  - Slowinski, Torsten
A1  - Hocher, Berthold
T1  - DNA methylation of the glucocorticoid receptor gene promoter in the placenta is associated with blood pressure regulation in human pregnancy
JF  - Journal of hypertension
N2  - Background: Blood pressure (BP) regulation during pregnancy is influenced by hormones of placental origin. It was shown that the glucocorticoid system is altered in hypertensive pregnancy disorders such as preeclampsia. Epigenetic mechanism might influence the activity of genes involved in placental hormone/hormone receptor synthesis/action during pregnancy. Method: In the current study, we analyzed the association of 50-C-phosphate-G-30 (CpG) site methylation of different glucocorticoid receptor gene (NR3C1) promoter regions with BP during pregnancy. The study was performed as a nested case-control study (n = 80) out of 1045 mother/ child pairs from the Berlin Birth Cohort. Placental DNA was extracted and bisulfite converted. Nested PCR products from six NR3C1 proximal promoter regions [glucocorticoid receptor gene promotor region B (GR-1B), C (GR-1C), D (GR-1D), E (GR-1E), F (GR-1F), and H (GR-1H)] were analyzed by next generation sequencing. Results: NR3C1 promoter regions GR-1D and GR-1E had a much higher degree of DNA methylation as compared to GR-1B, GR-1F or GR-1H when analyzing the entire study population. Comparison of placental NR3C1 CpG site methylation among hypotensive, normotensive and hypertensive mothers revealed several differently methylated CpG sites in the GR-1F promoter region only. Both hypertension and hypotension were associated with increased DNA methylation of GR-1F CpG sites. These associations were independent of confounding factors, such as family history of hypertension, smoking status before pregnancy and prepregnancy BMI. Assessment of placental glucocorticoid receptor expression by western blot showed that observed DNA methylation differences were not associated with altered levels of placental glucocorticoid receptor expression. However, correlation matrices of all NR3C1 proximal promoter regions demonstrated different correlation patterns of intraregional and interregional DNA methylation in the three BP groups, putatively indicating altered transcriptional control of glucocorticoid receptor isoforms. Conclusion: Our study provides evidence of an independent association between placental NR3C1 proximal promoter methylation and maternal BP. Furthermore, we observed different patterns of NR3C1 promoter methylation in normotensive, hypertensive and hypotensive pregnancy.
KW  - DNA methylation
KW  - epigenetics
KW  - glucocorticoid receptor
KW  - hypertension
KW  - hypotension
KW  - NR3C1 gene
KW  - placenta
KW  - pregnancy
Y1  - 2017
U6  - https://doi.org/10.1097/HJH.0000000000001450
SN  - 0263-6352
SN  - 1473-5598
VL  - 35
SP  - 2276
EP  - 2286
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  - 
TY  - JOUR
A1  - Reichetzeder, Christoph
A1  - von Websky, Karoline
A1  - Tsuprykov, Oleg
A1  - Samarin, Azadeh Mohagheghi
A1  - Falke, Luise Gabriele
A1  - Putra, Sulistyo Emantoko Dwi
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Antonenko, Viktoriia
A1  - Curato, Caterina
A1  - Rippmann, Joerg
A1  - Klein, Thomas
A1  - Hocher, Berthold
T1  - Head-to-head comparison of structurally unrelated dipeptidyl peptidase 4 inhibitors in the setting of renal ischemia reperfusion injury
JF  - British journal of pharmacology : journal of The British Pharmacological Society
N2  - BACKGROUND AND PURPOSE Results regarding protective effects of dipeptidyl peptidase 4 (DPP4) inhibitors in renal ischaemia-reperfusion injury (IRI) are conflicting. Here we have compared structurally unrelated DPP4 inhibitors in a model of renal IRI. EXPERIMENTAL APPROACH IRI was induced in uninephrectomizedmale rats by renal artery clamping for 30 min. The shamgroup was uninephrectomized but not subjected to IRI. DPP4 inhibitors or vehicle were given p. o. once daily on three consecutive days prior to IRI: linagliptin (1.5 mg.kg(-1).day(-1)), vildagliptin (8mg.kg(-1).day(-1)) and sitagliptin (30 mg.kg(-1).day(-1)). An additional group received sitagliptin until study end (before IRI: 30 mg.kg(-1).day(-1); after IRI: 15mg.kg(-1).day(-1)). KEY RESULTS Plasma-active glucagon-like peptide type 1 (GLP(-1)) increased threefold to fourfold in all DPP4 inhibitor groups 24 h after IRI. Plasma cystatin C, a marker of GFR, peaked 48 h after IRI. Compared with the placebo group, DPP4 inhibition did not reduce increased plasma cystatin C levels. DPP4 inhibitors ameliorated histopathologically assessed tubular damage with varying degrees of drug-specific efficacies. Renal osteopontin expression was uniformly reduced by all DPP4 inhibitors. IRI-related increased renal cytokine expression was not decreased by DPP4 inhibition. Renal DPP4 activity at study end was significantly inhibited in the linagliptin group, but only numerically reduced in the prolonged/dose-adjusted sitagliptin group. Active GLP(-1) plasma levels at study end were increased only in the prolonged/dose-adjusted sitagliptin treatment group. CONCLUSIONS AND IMPLICATIONS In rats with renal IRI, DPP4 inhibition did not alter plasma cystatin C, a marker of glomerular function, but may protect against tubular damage.
Y1  - 2017
U6  - https://doi.org/10.1111/bph.13822
SN  - 0007-1188
SN  - 1476-5381
VL  - 174
SP  - 2273
EP  - 2286
PB  - Wiley
CY  - Hoboken
ER  -