{
  "abstract": "Proper use of fingers and limbs is crucial for people to carry out normal activities of daily living. Therefore, when fingers or limbs are severed accidentally, replantation is attempted whenever possible. However, even when replantation is successful and fingers or limbs are preserved, functional limitations often arise due to contractures in reattached fingers or limbs, although mechanisms underlying contractures or countermeasures to ameliorate them are not well understood. Here, using a rat femoral artery ischemia-reperfusion (I/R) model, we show that oxidative stress caused by accumulation of oxidative DNA damage occurs in gastrocnemius and soleus muscles after I/R induces muscle cell apoptosis. Moreover, we demonstrate that administration of the antioxidant N-acetyl cysteine (NAC) significantly suppresses oxidative stress accumulation and apoptosis induction in both muscles. We observed that collagen fibers accumulate in the gastrocnemius and soleus muscles after I/R in our model, and that collagen fiber accumulation was significantly suppressed by NAC administration. We demonstrate that adding hydrogen peroxide (H2O2), a reactive oxygen species (ROS), to an in vitro C2C12 myoblast culture system significantly increased expression of the apoptosis-inducing factors Bcl-2-associated X protein (BAX) and Caspase 3, while co-treatment with NAC significantly counteracted this increase and increased expression of the anti-apoptotic factor B-cell lymphoma 2 (Bcl2). Also using the C2C12 myoblast culture system, we show that H2O2 significantly increased expression of Cellular Communication Network Factor 2 (CCN2), which induces fibrosis, while co-addition of NAC with H2O2 significantly suppressed CCN2 induction. Our findings shed light on mechanisms underlying I/R injury in limbs and suggest countermeasures.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hideto Matsunaga"
    },
    {
      "name": "Ryuji Yonemitsu"
    },
    {
      "name": "Katsumasa Ideo"
    },
    {
      "name": "Junnosuke Ide"
    },
    {
      "name": "Masaki Shimada"
    },
    {
      "name": "Makoto Tateyama"
    },
    {
      "name": "Xiao Tian"
    },
    {
      "name": "Shu Takata"
    },
    {
      "name": "Kosei Takata"
    },
    {
      "name": "Shuntaro Tanimura"
    },
    {
      "name": "Yuto Shibata"
    },
    {
      "name": "Naoto Yoshimura"
    },
    {
      "name": "Kazuya Maeda"
    },
    {
      "name": "Junki Kawakami"
    },
    {
      "name": "Takahiro Arima"
    },
    {
      "name": "Yuki Kai"
    },
    {
      "name": "Soichiro Karata"
    },
    {
      "name": "Hikaru Goshogawa"
    },
    {
      "name": "Satoshi Hisanaga"
    },
    {
      "name": "Kazuki Sugimoto"
    },
    {
      "name": "Hironori Tanoue"
    },
    {
      "name": "Masaki Yugami"
    },
    {
      "name": "Takayuki Nakamura"
    },
    {
      "name": "Yusuke Uehara"
    },
    {
      "name": "Tetsuro Masuda"
    },
    {
      "name": "Takuya Tokunaga"
    },
    {
      "name": "Tatsuki Karasugi"
    },
    {
      "name": "Takeshi Miyamoto"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f68hatkde3vhb.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0357829",
  "fulltext_url": null,
  "id": "f68hatkde3vhb",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0357829",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Body fluids/Blood/Blood flow"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Body limbs"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Cardiovascular anatomy/Blood vessels/Arteries/Femoral arteries"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell death/Apoptosis"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Stem cells/Myoblasts"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Oxidative stress"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Fibrosis"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Body fluids/Blood/Blood flow"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Physiological processes/Reperfusion"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Body fluids/Blood/Blood flow"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Body limbs"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Cardiovascular anatomy/Blood vessels/Arteries/Femoral arteries"
    ]
  ],
  "openalex": "W7212146641",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0357829&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-10",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/f68hatkde3vhb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "10.1371/journal.pone.0357829",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0357829"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    }
  ],
  "title": "N-acetylcysteine attenuates oxidative-stress-associated apoptosis and collagen deposition after rat hindlimb ischemia-reperfusion injury",
  "title_text": "N-acetylcysteine attenuates oxidative-stress-associated apoptosis and collagen deposition after rat hindlimb ischemia-reperfusion injury",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/f68hatkde3vhb",
  "venue": "PLOS One",
  "versions": []
}