{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T21:49:17Z","timestamp":1773524957771,"version":"3.50.1"},"reference-count":48,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:p>Creatine monohydrate (CrM) supplementation appears to be relatively safe based on data from short-term and intermediate-term human studies and results from several therapeutic trials. The purpose of the current study was to characterize pathological changes after intermediate-term and long-term CrM supplementation in mice [healthy control and SOD1 (G93A) transgenic] and rats (prednisolone and nonprednisolone treated). Histological assessment (18-20 organs\/tissues) was performed on G93A mice after 159 days, and in Sprague-Dawley rats after 365 days, of CrM supplementation (2% wt\/wt) compared with control feed. Liver histology was also evaluated in CD-1 mice after 300 days of low-dose CrM supplementation (0.025 and 0.05 g \u00b7 kg<jats:sup>-1<\/jats:sup>\u00b7 day<jats:sup>-1<\/jats:sup>) and in Sprague-Dawley rats after 52 days of CrM supplementation (2% wt\/wt) with and without prednisolone. Areas of hepatitis were observed in the livers of the CrM-supplemented G93A mice ( P &lt; 0.05), with no significant inflammatory lesions in any of the other 18-20 tissues\/organs that were evaluated. The CD-1 mice also showed significant hepatic inflammatory lesions ( P &lt; 0.05), yet there was no negative effect of CrM on liver histology in the Sprague-Dawley rats after intermediate-term or long-term supplementation nor was inflammation seen in any other tissues\/organs ( P = not significant). Dietary CrM supplementation can induce inflammatory changes in the liver of mice, but not rats. The observed inflammatory changes in the murine liver must be considered in the evaluation of hepatic metabolism in CrM-supplemented mice. Species differences must be considered in the evaluation of toxicological and physiological studies.<\/jats:p>","DOI":"10.1152\/ajpregu.00270.2003","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:31:29Z","timestamp":1425414689000},"page":"R762-R769","source":"Crossref","is-referenced-by-count":46,"title":["Histological assessment of intermediate- and long-term creatine monohydrate supplementation in mice and rats"],"prefix":"10.1152","volume":"285","author":[{"given":"M. A.","family":"Tarnopolsky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. M.","family":"Bourgeois","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Snow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Keys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. D.","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. M.","family":"Kwiecien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Turnbull","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00188.x"},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510250214"},{"key":"REF3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.1998.00427.x"},{"key":"REF4","doi-asserted-by":"crossref","unstructured":"Brewer GJand Wallimann TW.Protective effect of the energy precursor creatine against toxicity of glutamate and beta-amyloid in rat hippocampal neurons.J Neurochem74: 1968-1978, 2000.","DOI":"10.1046\/j.1471-4159.2000.0741968.x"},{"key":"REF5","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/58.1.B11"},{"key":"REF6","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4408"},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1999.277.3.R698"},{"key":"REF8","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2001.20590"},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-12-04389.2000"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(89)80067-0"},{"key":"REF11","doi-asserted-by":"publisher","DOI":"10.1042\/cs0840565"},{"key":"REF12","doi-asserted-by":"publisher","DOI":"10.1123\/ijsn.7.4.330"},{"key":"REF13","doi-asserted-by":"crossref","unstructured":"Guimbal Cand Kilimann MW.A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression.J Biol Chem268: 8418-8421, 1993.","DOI":"10.1016\/S0021-9258(18)52891-X"},{"key":"REF14","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005475206997"},{"key":"REF15","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.81.1.232"},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(01)01268-1"},{"key":"REF17","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10554"},{"key":"REF18","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8223(99)00145-5"},{"key":"REF19","doi-asserted-by":"publisher","DOI":"10.1097\/00042752-199810000-00007"},{"key":"REF20","doi-asserted-by":"publisher","DOI":"10.1038\/6568"},{"key":"REF21","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903113401017"},{"key":"REF22","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022469320296"},{"key":"REF23","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690045"},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.6164"},{"key":"REF25","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.9.1407"},{"key":"REF26","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201x.1998.00395.x"},{"key":"REF27","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7049"},{"key":"REF28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-01-00156.1998"},{"key":"REF29","doi-asserted-by":"publisher","DOI":"10.1097\/00005768-200002000-00007"},{"key":"REF30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.8.3304"},{"key":"REF31","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.91.3.1041"},{"key":"REF32","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(01)00273-5"},{"key":"REF33","doi-asserted-by":"publisher","DOI":"10.1097\/00005768-199908000-00005"},{"key":"REF34","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)79319-3"},{"key":"REF35","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01399-4"},{"key":"REF36","doi-asserted-by":"publisher","DOI":"10.1136\/bjsm.34.4.284"},{"key":"REF37","unstructured":"Schilling BK, Stone MH, Utter A, Kearney JT, Johnson M, Coglianese R, Smith L, O'Bryant HS, Fry AC, Starks M, Keith R, and Stone ME.Creatine supplementation and health variables: a retrospective study.Med Sci Sports Exerc33: 183-188, 2001."},{"key":"REF38","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000044405.29988.E1"},{"key":"REF39","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00212-4"},{"key":"REF40","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200011)48:5<723::AID-ANA5>3.0.CO;2-W"},{"key":"REF41","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.4.854"},{"key":"REF42","doi-asserted-by":"publisher","DOI":"10.1123\/ijsnem.10.4.452"},{"key":"REF43","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199712)20:12<1502::AID-MUS4>3.0.CO;2-C"},{"key":"REF44","doi-asserted-by":"publisher","DOI":"10.1097\/00005768-200003000-00024"},{"key":"REF45","doi-asserted-by":"publisher","DOI":"10.1042\/bj2810021"},{"key":"REF46","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.9.1848"},{"key":"REF47","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.1107"},{"key":"REF48","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(80)91432-1"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00270.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T09:31:57Z","timestamp":1651397517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpregu.00270.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10]]},"references-count":48,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,10]]}},"alternative-id":["10.1152\/ajpregu.00270.2003"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00270.2003","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10]]}}}