{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:33:50Z","timestamp":1776792830304,"version":"3.51.2"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,5,27]],"date-time":"2018-05-27T00:00:00Z","timestamp":1527379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["839867"],"award-info":[{"award-number":["839867"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1I21RX000353\u201001A2"],"award-info":[{"award-number":["1I21RX000353\u201001A2"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Fracture healing in alcoholics is delayed and often associated with infections resulting in prolonged rehabilitation. It has been reported that binge drinking of alcohol increases oxidative stress and delays fracture healing in rats, which is prevented by treatment with the antioxidant n\u2010acetyl cysteine (NAC). Oxidative stress is a significant factor in pathologies of various organs resulting from chronic alcoholism. Therefore, we hypothesize that treatment with NAC reduces oxidative stress and restores fracture healing in chronic alcoholics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rats (10\u00a0months old) were pair\u2010fed the Lieber\u2010DeCarli ethanol (EtOH) diet or control diet for 16\u00a0weeks. A closed fracture was performed and rats allowed to recover for 72\u00a0hours. Rats were divided into 4 groups\u2014control, control\u00a0+\u00a0NAC, EtOH, and EtOH\u00a0+\u00a0NAC\u2014and injected intraperitoneally with 200\u00a0mg\/kg of NAC daily for 3\u00a0days. Serum and bone fracture callus homogenates were collected and assayed for traditional markers of inflammation, oxidative stress, and bone regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The oxidative stress marker malondialdehyde (MDA) was increased in both serum and bone tissue in EtOH\u2010fed animals compared to controls. NAC treatment significantly (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01) reduced MDA to near normal levels and dramatically increased the index of antioxidant efficacy (catalase\/MDA ratio) (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01). Inflammatory markers tumor necrosis factor\u2010\u03b1, interferon\u2010\u03b3, and interleukin\u20106 were significantly decreased in serum and callus following NAC treatment. NAC treatment reduced EtOH\u2010induced bone resorption as evidenced by significant decreases in C\u2010telopeptide of type\u2010I\u2010collagen levels (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) and band\u20105 tartrate\u2010resistant acid phosphatase levels in the tissue (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Oxidative stress and excessive inflammation are involved in the inhibition of fracture healing by EtOH. In this study, early short\u2010term treatment of EtOH\u2010fed animals with the antioxidant NAC reduced oxidative stress and normalized the innate immune response to fracture in the early phase of fracture healing, thereby restoring the normal onset of bone regeneration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13765","type":"journal-article","created":{"date-parts":[[2018,4,26]],"date-time":"2018-04-26T19:59:51Z","timestamp":1524772791000},"page":"1206-1216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["N\u2010Acetyl Cysteine Treatment Restores Early Phase Fracture Healing in Ethanol\u2010Fed Rats"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9104-2238","authenticated-orcid":false,"given":"Michael J.","family":"Duryee","sequence":"first","affiliation":[{"name":"Veteran Affairs Nebraska\u2010Western Iowa Health Care System  Omaha Nebraska"},{"name":"Department of Internal Medicine  Division of Rheumatology University of Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anand","family":"Dusad","sequence":"additional","affiliation":[{"name":"Veteran Affairs Nebraska\u2010Western Iowa Health Care System  Omaha Nebraska"},{"name":"Department of Internal Medicine  Division of Rheumatology University of Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos D.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Veteran Affairs Nebraska\u2010Western Iowa Health Care System  Omaha Nebraska"},{"name":"Department of Internal Medicine  Division of Rheumatology University of Nebraska Medical Center Omaha Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kusum K.","family":"Kharbanda","sequence":"additional","affiliation":[{"name":"Veteran Affairs Nebraska\u2010Western Iowa Health Care System  Omaha 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