{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:54:01Z","timestamp":1785779641303,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A novel pleuromutilin derivative, compound\n                    <jats:bold>4g<\/jats:bold>\n                    with a cyclobutyl side chain, was identified and found to have good antibacterial activity, including methicillin\u2010resistant\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    (MRSA) and\n                    <jats:italic>Mycoplasma<\/jats:italic>\n                    . In order to evaluate its safety profile, acute and 28\u2010day oral toxicity studies were carried out. An acute toxicity study in rats revealed that the oral LD\n                    <jats:sub>50<\/jats:sub>\n                    of\n                    <jats:bold>4g<\/jats:bold>\n                    exceeded 5000\u2009mg\/kg, indicating that the compound had low acute toxicity. In a 28\u2010day oral toxicity test, the rats were repeatedly administered 0, 300, 1000, and 3000\u2009mg\/kg doses and showed no adverse clinical symptoms or death. Although\n                    <jats:bold>4g<\/jats:bold>\n                    did not affect body weight, hematological findings indicated dose\u2010dependent inflammatory changes at 1000 and 3000\u2009mg\/kg. Serum biochemistry showed decreases in alanine aminotransferase (ALT) and alkaline phosphatase (ALP), suggesting adaptive metabolic responses rather than classic hepatocellular injury. Significantly, dose\u2010dependent increases in relative liver weight were observed at all dose levels, accompanied by minimal hepatocyte steatosis and altered serum lipid profiles, identifying the liver as a primary target organ. Based on the totality of findings, the no\u2010observed\u2010adverse\u2010effect level (NOAEL) was determined to be 300\u2009mg\/kg. In conclusion, pleuromutilin derivative 4g has low toxicity, which provides the theoretical basis to further investigate for a new candidate drug.\n                  <\/jats:p>","DOI":"10.1002\/jat.70104","type":"journal-article","created":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T23:40:02Z","timestamp":1771198802000},"page":"3090-3101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acute and 28\u2010Day Toxicity Evaluation of New Pleuromutilin Derivative 4g"],"prefix":"10.1002","volume":"46","author":[{"given":"He\u2010Chao","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Gansu Agricultural University  Lanzhou China"},{"name":"Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhun","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-9169","authenticated-orcid":false,"given":"Wen\u2010Bo","family":"Ge","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3317-0666","authenticated-orcid":false,"given":"Jian\u2010Yong","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Gansu Agricultural University  Lanzhou China"},{"name":"Key Laboratory of New Animal Drug of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1191\/0960327102ht247oa"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)44820\u2010X"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2319"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2012.11.021"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.11.006"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0040\u20104020(80)80078\u20100"},{"issue":"5","key":"e_1_2_10_8_1","first-page":"25","article-title":"Mecanismos de hepatotoxicidade [Mechanisms of hepatotoxicity]","volume":"85","author":"Bertolami M. 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