{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:44:44Z","timestamp":1747183484632,"version":"3.40.5"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013076","name":"National Major Science and Technology Projects of China","doi-asserted-by":"publisher","award":["2018ZX10715008"],"award-info":[{"award-number":["2018ZX10715008"]}],"id":[{"id":"10.13039\/501100013076","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":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>A combination of zidovudine (AZT), lamivudine (3TC) and lopinavir\/ritonavir (LPV\/r) is one of the most effective drugs for preventing mother\u2010to\u2010child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT\u2009+\u20093TC\u2009+\u2009LPV\/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28\u2010day feeding test was conducted to assess the potential subacute toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In mice, the LD<jats:sub>50<\/jats:sub> of the AZT\u2009+\u20093TC\u2009+\u2009LPV\/r mixture was greater than 2000\u2009mg\/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose\u2010dependent manner in mice (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). After treatment with AZT\u2009+\u20093TC\u2009+\u2009LPV\/r for 28\u2009days, the BW gain of male and female rats in the high\u2010dose group was lower than that in the control group (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05); the relative weights of the liver, kidney, spleen and brain increased (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high\u2010dose group. The haemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high\u2010dose group increased (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). The total protein, albumin, cholesterol and blood glucose levels of male and female rats in the high\u2010dose group were significantly decreased (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium\u2010 and high\u2010dose groups increased significantly (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results suggest that AZT\u2009+\u20093TC\u2009+\u2009LPV\/r may exhibit genotoxicity and subacute toxicity under experimental conditions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcpt.13870","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T04:24:41Z","timestamp":1680668681000},"page":"82-97","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Short\u2010term toxicity assessment of combined use of zidovudine, lamivudine and lopinavir\/ritonavir in vitro and in 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