{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T09:32:05Z","timestamp":1768296725392,"version":"3.49.0"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mahidol University","award":["BRF-1-061\/2565"],"award-info":[{"award-number":["BRF-1-061\/2565"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Primaquine (PQ) is the only antimalarial medication used to eradicate many species of Plasmodium gametocytes and prevent relapse in vivax and ovale malarias. PQ metabolites induce oxidative stress and impair parasitic mitochondria, leading to protozoal growth retardation and death. Collateral damage is also presented in mammalian host cells, particularly erythrocytes, resulting in hemolysis and tissue destruction. However, the underlying mechanisms of these complications, particularly the mitochondria-mediated cell death of the host, are poorly understood. In the present study, toxicopathological studies were conducted on a rat model to determine the effect of PQ on affected tissues and mitochondrial toxicity. The results indicated that the LD50 for PQ is 200 mg\/kg. A high dose of PQ induced hemolytic anemia, elevated a hepatic enzyme (SGPT), and induced proximal tubular degeneration, ventricular cardiomyopathy, and mitochondrial dysregulation. In addition, PQ induced the upregulation of apoptosis-related proteins Drp-1 and caspase-3, with a positive correlation, as well as the pro-apoptotic mitochondrial gene expression of Bax, reflecting the toxic effect of high doses of PQ on cellular damage and mitochondrial apoptosis in terms of hepatotoxicity, nephrotoxicity, and cardiotoxicity. Regarding the risk\/benefit ratio of drug administration, our research provides caution for the use of PQ in the treatment of malaria based on its toxicopathological effects.<\/jats:p>","DOI":"10.3390\/toxics11020146","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T01:40:25Z","timestamp":1675388425000},"page":"146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["High-Dose Primaquine Induces Proximal Tubular Degeneration and Ventricular Cardiomyopathy Linked to Host Cells Mitochondrial Dysregulation"],"prefix":"10.3390","volume":"11","author":[{"given":"Atthasit","family":"Rabiablok","sequence":"first","affiliation":[{"name":"Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, 420\/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8729-1442","authenticated-orcid":false,"given":"Borimas","family":"Hanboonkunupakarn","sequence":"additional","affiliation":[{"name":"Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, 420\/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khwanchanok","family":"Tuentam","sequence":"additional","affiliation":[{"name":"Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420\/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamonpan","family":"Fongsodsri","sequence":"additional","affiliation":[{"name":"Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420\/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tapanee","family":"Kanjanapruthipong","sequence":"additional","affiliation":[{"name":"Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420\/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumate","family":"Ampawong","sequence":"additional","affiliation":[{"name":"Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420\/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"The Lancet (2022). 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