{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:05:55Z","timestamp":1773659155555,"version":"3.50.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2018,12,8]],"date-time":"2018-12-08T00:00:00Z","timestamp":1544227200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Amino Acids"],"published-print":{"date-parts":[[2019,3]]},"DOI":"10.1007\/s00726-018-2684-6","type":"journal-article","created":{"date-parts":[[2018,12,8]],"date-time":"2018-12-08T11:54:27Z","timestamp":1544270067000},"page":"483-494","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacological activation of dimethylarginine dimethylaminohydrolase (DDAH) activity by inorganic nitrate and DDAH inhibition by NG-hydroxy-l-arginine, N\u03c9,N\u03c9-dimethyl-l-citrulline and N\u03c9,N\u03c9-dimethyl-N\u03b4-hydroxy-l-citrulline: results and overview"],"prefix":"10.1007","volume":"51","author":[{"given":"Alexander","family":"Bollenbach","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitrios","family":"Tsikas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,12,8]]},"reference":[{"key":"2684_CR1","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1161\/01.ATV.0000081742.92006.59","volume":"23","author":"V Achan","year":"2003","unstructured":"Achan V, Broadhead M, Malaki M, Whitley G, Leiper J, MacAllister R, Vallance P (2003) Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 23:1455\u20131459","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2684_CR2","doi-asserted-by":"publisher","first-page":"4715","DOI":"10.1113\/jphysiol.2014.275263","volume":"592","author":"T Ashmore","year":"2014","unstructured":"Ashmore T, Fernandez BO, Branco-Price C, West JA, Cowburn AS, Heather LC, Griffin JL, Johnsen RS, Feelisch M, Murray AJ (2014) Dietary nitrate increasing arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart. J Physiol 592:4715\u20134731","journal-title":"J Physiol"},{"key":"2684_CR3","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.diabres.2014.08.028","volume":"106","author":"F Bal","year":"2014","unstructured":"Bal F, Bekpinar S, Unlucerci Y, Kusku-Kiraz Z, \u00d6nder S, Uysal M, Gurdol F (2014) Antidiabetic drug metformin is effective on the metabolism of asymmetric dimethylarginine in experimental liver injury. Diabetes Res Clin Pract 106:295\u2013302","journal-title":"Diabetes Res Clin Pract"},{"key":"2684_CR4","doi-asserted-by":"publisher","first-page":"4791","DOI":"10.1021\/bi972312t","volume":"37","author":"R Bogumil","year":"1998","unstructured":"Bogumil R, Knipp M, Fundel SM, Vas\u00e1k M (1998) Characterization of dimethylargininase from bovine brain: evidence for a zinc binding site. Biochemistry 37:4791\u20134798","journal-title":"Biochemistry"},{"key":"2684_CR5","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1006\/bbrc.1994.2371","volume":"203","author":"JL Boucher","year":"1994","unstructured":"Boucher JL, Custot J, Vadon S, Delaforge M, Lepoivre M, Tenu JP, Yapo A, Mansuy D (1994) N omega-hydroxyl-l-arginine, an intermediate in the l-arginine to nitric oxide pathway, is a strong inhibitor of liver and macrophage arginase. Biochem Biophys Res Commun 203:1614\u20131621","journal-title":"Biochem Biophys Res Commun"},{"key":"2684_CR6","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1093\/cvr\/cvq366","volume":"89","author":"M Carlstr\u00f6m","year":"2011","unstructured":"Carlstr\u00f6m M, Persson AE, Larsson E, Hezel M, Scheffer PG, Teerlink T, Weitzberg E, Lundberg JO (2011) Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension. Cardiovasc Res 89:574\u2013585","journal-title":"Cardiovasc Res"},{"key":"2684_CR7","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.jchromb.2007.08.002","volume":"858","author":"K Chobanyan","year":"2007","unstructured":"Chobanyan K, Thum T, Suchy MT, Zhu B, Mitschke A, Gutzki FM, Beckmann B, Stichtenoth DO, Tsikas D (2007) GC-MS assay for hepatic DDAH activity in diabetic and non-diabetic rats by measuring dimethylamine (DMA) formed from asymmetric dimethylarginine (ADMA): evaluation of the importance of S-nitrosothiols as inhibitors of DDAH activity in vitro and in vivo in humans. J Chromatogr B 858:32\u201341","journal-title":"J Chromatogr B"},{"key":"2684_CR8","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.abb.2010.02.004","volume":"496","author":"L Costanzo Di","year":"2010","unstructured":"Di Costanzo L, Ilies M, Thorn KJ, Christianson DW (2010) Inhibition of human arginase I by substrate and product analogues. Arch Biochem Biophys 496:101\u2013108","journal-title":"Arch Biochem Biophys"},{"key":"2684_CR9","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1111\/bcpt.12569","volume":"119","author":"AK Erenler","year":"2016","unstructured":"Erenler AK, Do\u011fan T, Ko\u00e7ak C, Ece Y (2016) Investigation of toxic effects of mushroom poisoning on the cardiovascular system. Basic Clin Pharmacol Toxicol 119:317\u2013321","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"2684_CR10","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1093\/eurheartj\/ehr304","volume":"33","author":"U F\u00f6rstermann","year":"2012","unstructured":"F\u00f6rstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33:829\u2013837","journal-title":"Eur Heart J"},{"key":"2684_CR11","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1002\/ange.19840960127","volume":"96","author":"B Fugmann","year":"1984","unstructured":"Fugmann B, Steglich W (1984) Ungew\u00f6hnliche Inhaltsstoffe des B\u00e4tterpilzes Lyophyllum connatum (Agaricales). Angew Chem 96:71\u201372","journal-title":"Angew Chem"},{"key":"2684_CR12","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0014-5793(96)00997-0","volume":"395","author":"SM Fundel","year":"1996","unstructured":"Fundel SM, Pountney DL, Bogumil R, Gehrig PM, Hasler DW, Faller P, Vas\u00e1k M (1996) Isolation and characterization of a novel monomeric zinc- and heme-containing protein from bovine brain. FEBS Lett 395:33\u201338","journal-title":"FEBS Lett"},{"key":"2684_CR13","doi-asserted-by":"publisher","first-page":"81","DOI":"10.2165\/11534750-000000000-00000","volume":"50","author":"GG Graham","year":"2011","unstructured":"Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ, Greenfield JR, Greenup LC, Kirkpatrick CM, Ray JE, Timmins P, Williams KM (2011) Clinical pharmacokinetics of metformin. Clin Pharmacokinet 50:81\u201398","journal-title":"Clin Pharmacokinet"},{"key":"2684_CR14","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1007\/s00726-018-2614-7","volume":"50","author":"E Hanff","year":"2018","unstructured":"Hanff E, Hafner P, Bollenbach A, Bonati U, Kayacelebi AA, Fischer D, Tsikas D (2018) Effects of single and combined metformin and L-citrulline supplementation on l-arginine-related pathways in Becker muscular dystrophy patients: possible biochemical and clinical implications. Amino Acids 50:1391\u20131406","journal-title":"Amino Acids"},{"key":"2684_CR15","doi-asserted-by":"publisher","first-page":"3373","DOI":"10.1093\/emboj\/16.12.3373","volume":"16","author":"A Humm","year":"1997","unstructured":"Humm A, Fritsche E, Steinbacher S, Huber R (1997) Crystal structure and mechanism of human l-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. EMBO J 16:3373\u20133385","journal-title":"EMBO J"},{"key":"2684_CR16","doi-asserted-by":"publisher","first-page":"3092","DOI":"10.1161\/01.CIR.99.24.3092","volume":"99","author":"A Ito","year":"1999","unstructured":"Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP (1999) Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 99:3092\u20133095","journal-title":"Circulation"},{"key":"2684_CR17","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1161\/HYPERTENSIONAHA.110.153536","volume":"56","author":"V Kapil","year":"2010","unstructured":"Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F, Arghandawi S, Pearl V, Benjamin N, Loukogeorgakis S, Macallister R, Hobbs AJ, Webb AJ, Ahluwalia A (2010) Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension 56:274\u2013281","journal-title":"Hypertension"},{"key":"2684_CR18","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.niox.2007.05.005","volume":"17","author":"A Kielstein","year":"2007","unstructured":"Kielstein A, Tsikas D, Galloway GP, Mendelson JE (2007) Asymmetric dimethylarginine (ADMA)\u2014modulator of nociception in opiate tolerance and addiction? Nitric Oxide 17:55\u201359","journal-title":"Nitric Oxide"},{"key":"2684_CR19","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1046\/j.1432-1327.1998.2580863.x","volume":"258","author":"M Kimoto","year":"1998","unstructured":"Kimoto M, Miyatake S, Sasagawa T, Yamashita H, Okita M, Oka T, Ogawa T, Tsuji H (1998) Purification, cDNA cloning and expression of human NG, NG-dimethylarginine dimethylaminohydrolase. Eur J Biochem 258:863\u2013868","journal-title":"Eur J Biochem"},{"key":"2684_CR20","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1271\/bbb.69.357","volume":"69","author":"C Kimura","year":"2005","unstructured":"Kimura C, Nukina M, Igarashi K, Sugawara Y (2005) beta-Hydroxyergothioneine, a new ergothioneine derivative from the mushroom Lyophyllum connatum, and its protective activity against carbon tetrachloride-induced injury in primary culture hepatocytes. Biosci Biotechnol Biochem 69:357\u2013363","journal-title":"Biosci Biotechnol Biochem"},{"key":"2684_CR21","doi-asserted-by":"publisher","first-page":"40449","DOI":"10.1074\/jbc.M104056200","volume":"276","author":"M Knipp","year":"2001","unstructured":"Knipp M, Charnock JM, Garner CD, Vas\u00e1k M (2001) Structural and functional characterization of the Zn(II) site in dimethylargininase-1 (DDAH-1) from bovine brain. Zn(II) release activates DDAH-1. J Biol Chem 276:40449\u201340456","journal-title":"J Biol Chem"},{"key":"2684_CR22","doi-asserted-by":"publisher","first-page":"13527","DOI":"10.1073\/pnas.212269799","volume":"99","author":"J Leiper","year":"2002","unstructured":"Leiper J, Murray-Rust J, McDonald N, Vallance P (2002) S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proc Natl Acad Sci U S A 99:13527\u201313532","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2684_CR23","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/nm1543","volume":"13","author":"J Leiper","year":"2007","unstructured":"Leiper J, Nandi M, Torondel B, Murray-Rust J, Malaki M, O\u2019Hara B, Rossiter S, Anthony S, Madhani M, Selwood D, Smith C, Wojciak-Stothard B, Rudiger A, Stidwill R, McDonald NQ, Vallance P (2007) Disruption of methylarginine metabolism impairs vascular homeostasis. Nat Med 13:198\u2013203","journal-title":"Nat Med"},{"key":"2684_CR24","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.jchromb.2007.01.020","volume":"851","author":"R Maas","year":"2007","unstructured":"Maas R, Tan-Andreesen J, Schwedhelm E, Schulze F, B\u00f6ger RH (2007) A stable-isotope based technique for the determination of dimethylarginine dimethylaminohydrolase (DDAH) activity in mouse tissue. J Chromatogr B 851:220\u2013228","journal-title":"J Chromatogr B"},{"key":"2684_CR25","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1111\/j.1476-5381.1996.tb16069.x","volume":"119","author":"RJ MacAllister","year":"1996","unstructured":"MacAllister RJ, Parry H, Kimoto M, Ogawa T, Russell RJ, Hodson H, Whitley GS, Vallance P (1996) Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. Br J Pharmacol 119:1533\u20131540","journal-title":"Br J Pharmacol"},{"key":"2684_CR26","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1111\/j.1432-1033.1992.tb17490.x","volume":"210","author":"S Mangani","year":"1992","unstructured":"Mangani S, H\u00e5kansson K (1992) Crystallographic studies of the binding of protonated and unprotonated inhibitors to carbonic anhydrase using hydrogen sulphide and nitrate anions. Eur J Biochem 210:867\u2013871","journal-title":"Eur J Biochem"},{"key":"2684_CR27","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1016\/j.fct.2008.01.010","volume":"46","author":"SC Mitchell","year":"2008","unstructured":"Mitchell SC, Zhang AQ, Smith RL (2008) Dimethylamine and diet. Food Chem Toxicol 46:1734\u20131738","journal-title":"Food Chem Toxicol"},{"key":"2684_CR28","doi-asserted-by":"publisher","first-page":"E615","DOI":"10.3390\/molecules21050615","volume":"21","author":"RB Murphy","year":"2016","unstructured":"Murphy RB, Tommasi S, Lewis BC, Mangoni AA (2016) Inhibitors of the hydrolytic enzyme dimethylarginine dimethylaminohydrolase (DDAH): discovery, synthesis and development. Molecules 21:E615. https:\/\/doi.org\/10.3390\/molecules21050615","journal-title":"Molecules"},{"key":"2684_CR29","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/90387","volume":"8","author":"J Murray-Rust","year":"2001","unstructured":"Murray-Rust J, Leiper J, McAlister M, Phelan J, Tilley S, Santa Maria J, Vallance P, McDonald N (2001) Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase. Nat Struct Biol 8:679\u2013683 (Erratum in: Nat Struct Biol 8:818)","journal-title":"Nat Struct Biol"},{"key":"2684_CR30","doi-asserted-by":"crossref","first-page":"10205","DOI":"10.1016\/S0021-9258(18)81786-0","volume":"264","author":"T Ogawa","year":"1989","unstructured":"Ogawa T, Kimoto M, Sasaoka K (1989) Purification and properties of a new enzyme, NG, NG-dimethylarginine dimethylaminohydrolase, from rat kidney. J Biol Chem 264:10205\u201310209","journal-title":"J Biol Chem"},{"key":"2684_CR31","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.niox.2013.02.080","volume":"30","author":"L Servillo","year":"2013","unstructured":"Servillo L, Giovane A, Cautela D, Castaldo D, Balestrieri ML (2013) The methylarginines NMMA, ADMA, and SDMA are ubiquitous constituents of the main vegetables of human nutrition. Nitric Oxide 30:43\u201348","journal-title":"Nitric Oxide"},{"key":"2684_CR32","doi-asserted-by":"publisher","first-page":"5618","DOI":"10.1021\/bi052595m","volume":"45","author":"EM Stone","year":"2006","unstructured":"Stone EM, Costello AL, Tierney DL, Fast W (2006) Substrate-assisted cysteine deprotonation in the mechanism of dimethylargininase (DDAH) from Pseudomonas aeruginosa. Biochemistry 45:5618\u20135630","journal-title":"Biochemistry"},{"key":"2684_CR33","doi-asserted-by":"publisher","first-page":"16","DOI":"10.15586\/jcbmr.2017.22","volume":"3","author":"D Tsikas","year":"2017","unstructured":"Tsikas D (2017) Does the inhibitory action of asymmetric dimethylarginine (ADMA) on the endotelial nitric oxide synthase activity explain its importance in the cardiovascular system? The ADMA paradox. J Controv Biomed Res 3:16\u201322","journal-title":"J Controv Biomed Res"},{"key":"2684_CR34","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/ki.2008.360","volume":"74","author":"D Tsikas","year":"2008","unstructured":"Tsikas D, Chobanyan K (2008) Pitfalls in the measurement of tissue DDAH activity: is DDAH sensitive to nitrosative and oxidative stress? Kidney Int 74:969 (author reply 969-70)","journal-title":"Kidney Int"},{"key":"2684_CR35","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/S0378-4347(00)00142-0","volume":"742","author":"D Tsikas","year":"2000","unstructured":"Tsikas D, Sandmann J, Savva A, Luessen P, B\u00f6ger RH, Gutzki FM, Mayer B, Fr\u00f6lich JC (2000a) Assessment of nitric oxide synthase activity in vitro and in vivo by gas chromatography-mass spectrometry. J Chromatogr B Biomed 742:143\u2013153","journal-title":"J Chromatogr B Biomed"},{"key":"2684_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0014-5793(00)01686-0","volume":"478","author":"D Tsikas","year":"2000","unstructured":"Tsikas D, B\u00f6ger RH, Sandmann J, Bode-B\u00f6ger SM, Fr\u00f6lich JC (2000b) Endogenous nitric oxide synthase inhibitors are responsible for the l-arginine paradox. FEBS Lett 478:1\u20133","journal-title":"FEBS Lett"},{"key":"2684_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12933-017-0656-x","volume":"17","author":"D Tsikas","year":"2018","unstructured":"Tsikas D, Bollenbach A, Hanff E, Kayacelebi AA (2018a) Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and homoarginine (hArg): the ADMA, SDMA and hArg paradoxes. Cardiovasc Diabetol 17:1","journal-title":"Cardiovasc Diabetol"},{"key":"2684_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpha.2017.12.003","volume":"8","author":"D Tsikas","year":"2018","unstructured":"Tsikas D, Schwedhelm KS, Surdacki A, Giustarini D, Rossi R, Kukoc-Modun L, Kedia G, \u00dcckert S (2018b) S-Nitroso-N-acetyl-l-cysteine ethyl ester (SNACET) and N-acetyl-l-cysteine ethyl ester (NACET)-cysteine-based drug candidates with unique pharmacological profiles for oral use as NO, H2S and GSH suppliers and as antioxidants: results and overview. J Pharm Anal 8:1\u20139","journal-title":"J Pharm Anal"},{"key":"2684_CR39","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1042\/BJ20131666","volume":"460","author":"Z Wang","year":"2014","unstructured":"Wang Z, Lambden S, Taylor V, Sujkovic E, Nandi M, Tomlinson J, Dyson A, McDonald N, Caddick S, Singer M, Leiper J (2014) Pharmacological inhibition of DDAH1 improves survival, haemodynamics and organ function in experimental septic shock. Biochem J 460:309\u2013316","journal-title":"Biochem J"},{"key":"2684_CR40","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.ejphar.2016.07.034","volume":"789","author":"G W\u00f3jcicka","year":"2016","unstructured":"W\u00f3jcicka G, Jamroz-Wi\u015bniewska A, Czechowska G, Korolczuk A, Marciniak S, Be\u0142towski J (2016) The paraoxonase 1 (PON1), platelet-activating factor acetylohydrolase (PAF-AH) and dimethylarginine dimethylaminohydrolase (DDAH) activity in the metformin treated normal and diabetic rats. Eur J Pharmacol 789:187\u2013194","journal-title":"Eur J Pharmacol"}],"container-title":["Amino Acids"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00726-018-2684-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00726-018-2684-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00726-018-2684-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T22:31:03Z","timestamp":1662589863000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00726-018-2684-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,8]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["2684"],"URL":"https:\/\/doi.org\/10.1007\/s00726-018-2684-6","relation":{},"ISSN":["0939-4451","1438-2199"],"issn-type":[{"value":"0939-4451","type":"print"},{"value":"1438-2199","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,8]]},"assertion":[{"value":"17 August 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 December 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that there are no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Rats received humane care and the study protocol complied with the institutional guidelines of the Hannover Medical School.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statement"}}]}}