{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:05Z","timestamp":1787013905387,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T00:00:00Z","timestamp":1553472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573793"],"award-info":[{"award-number":["81573793"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    High\u2010dose cyclophosphamide (HD\u2010CTX) treatment often leads to severe nephrotoxicity and neurotoxicity, which are mainly caused by one of its metabolites, chloroacetaldehyde (CAA). However, there are no effective antidotes to prevent these side effects. The objective of this study was to evaluate the effect of Wuzhi Capsule (WZC) on the pharmacokinetics of CTX and its metabolites in rats, and the attenuation of CAA induced kidney and brain injuries, which was produced at equimolar with 2\u2010dechloroethylcyclophosphamide. Rats were treated with single\u2010 or multiple\u2010dose of WZC when giving HD\u2010CTX, and the plasma concentration of CTX and its metabolites were quantitated by UHPLC\u2010MS\/MS Single\u2010dose, not multiple\u2010dose of WZC co\u2010administration (300\u00a0mg\/kg) significantly reduced\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>0\u219224\u00a0h<\/jats:sub>\n                    of DC\u2010CTX by 33.10% and 35.51%, respectively. Biochemical assay suggested oxidative stress was involved in kidney and brain injuries by HD\u2010CTX, which were attenuated by single\u2010dose WZC (300\u00a0mg\/kg) pre\u2010treatment, with increased glutathione, glutathione peroxidase and superoxide dismutase contents\/or activities in both tissues and plasma (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.05). Meanwhile, WZC pre\u2010treatment could also significantly decrease the plasma levels of creatinine, blood urea nitrogen and malondialdehyde (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.05). Additionally, WZC treatment improved the morphology and pathology condition of the kidneys and brains in rats. In conclusion, single\u2010dose WZC co\u2010administration decreased CAA production and exerted protective effect on CTX\u2010induced oxidative stress in kidney and brain, whereas repetitive WZC co\u2010administration with CTX was probably not recommended.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.13211","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T01:13:42Z","timestamp":1550798022000},"page":"142-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Wuzhi capsule regulates chloroacetaldehyde pharmacokinetics behaviour and alleviates high\u2010dose cyclophosphamide\u2010induced nephrotoxicity and neurotoxicity in rats"],"prefix":"10.1111","volume":"125","author":[{"given":"Li","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"},{"name":"Key Laboratory of Jiangxi Province for Research on Active Ingredients in Natural Medicines, Bioengineering Research Institute Yichun University Yichun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jiangxi Province for Research on Active Ingredients in Natural Medicines, Bioengineering Research Institute Yichun University Yichun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyun","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiu","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"},{"name":"School of Traditional Chinese Material Shenyang Pharmaceutical University Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouhong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"},{"name":"Key Laboratory of Jiangxi Province for Research on Active Ingredients in Natural Medicines, Bioengineering Research Institute Yichun University Yichun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wansheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,25]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"142","article-title":"Oxazaphosphorine cytostatics: past\u2010present\u2010future. 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