{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:37:56Z","timestamp":1786721876482,"version":"build-2736575974"},"reference-count":143,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chemotherapy-induced hepatorenal toxicity is one of the most predominant dose-limiting obstacles in oncological pharmacotherapy, and the molecular mechanisms surrounding its pathogenesis are still poorly defined. Lipid peroxide toxicity-induced, iron-dependent, nonapoptotic types of regulated cell death called ferroptosis have emerged as a mechanically important process in the organ injury caused by chemotherapy. In this Keynote Review, we will summarize recent evidence showing the implication of ferroptosis in liver and kidney toxicity of platinum-based drugs, anthracycline drugs, tyrosine kinase inhibitors, and some targeted drugs. We identify key mechanisms underlying ferroptosis, including abnormalities of the axis of system Xc\u2013\/glutathione peroxidase4 (GPX4) axis, changes in iron homeostasis, and activation of ferritinophagy and the maladaptive effects of polyunsaturated fatty acid oxidation. The role of the hepatorenal microenvironment is discussed in detail, with a particular focus on mitochondrion-related abnormalities, interaction between endocrine and immune cells, and mitochondrion-endoplasmic reticulum-stress coupling, as well as interactions with ferroptosis suppressor protein 1 (FSP1)\/CoQ10 and dihydroorotate dehydrogenase (DHODH) pathways. Data from the preclinical models are combined with new treatment data to develop a linear toxicological story. The utility of the use of biomarker strategies such as plasma malondialdehyde, 4-hydroxynonenal adducts, circulating GPX4, and urinary prostaglandin-like isoprostanes in diagnosis and monitoring is examined. The role of therapeutic interventions such as Nrf2 activators, liproxstatin1, ferrostatin1, and iron chelators for reducing organ-specific ferroptotic injury without reducing effectiveness as antineoplastic is briefly explored. This Review highlights ferroptosis as a therapeutic target that is amenable to therapy and suggests a systematic approach for its integration into toxicological risk classifications during drug development for cancer treatment.<\/jats:p>","DOI":"10.1021\/acsptsci.6c00303","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:34:37Z","timestamp":1783701277000},"page":"2117-2136","source":"Crossref","is-referenced-by-count":0,"title":["Emerging Role of\nFerroptosis in Chemotherapy-Associated\nHepatorenal Toxicity: Mechanistic Insights and Toxicological Perspectives"],"prefix":"10.1021","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-1561","authenticated-orcid":true,"given":"Vanktesh","family":"Kumar","sequence":"first","affiliation":[{"name":"Lovely Professional University , , Jalandhar-Delhi G.T. Road , , ,","place":["Phagwara, Punjab, India, 144411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stalin","family":"Arulsamy","sequence":"additional","affiliation":[{"name":"Lovely Professional University , , Jalandhar-Delhi G.T. Road , , ,","place":["Phagwara, Punjab, India, 144411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wajid Aslam","family":"Khan","sequence":"additional","affiliation":[{"name":"Lovely Professional University , , Jalandhar-Delhi G.T. Road , , ,","place":["Phagwara, Punjab, India, 144411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3903-2048","authenticated-orcid":true,"given":"Shivank","family":"Sharma","sequence":"additional","affiliation":[{"name":"Lovely Professional University , , Jalandhar-Delhi G.T. Road , , ,","place":["Phagwara, Punjab, India, 144411"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinky","family":"Arora","sequence":"additional","affiliation":[{"name":"Lovely Professional University , , Jalandhar-Delhi G.T. Road , , ,","place":["Phagwara, Punjab, India, 144411"]},{"name":"CT University , , , ,","place":["Ludhiana, Punjab, India, 142024"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8407-4693","authenticated-orcid":true,"given":"Shubham","family":"Kumar","sequence":"additional","affiliation":[{"name":"Lovely Professional University , , Jalandhar-Delhi G.T. 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Toxicol."},{"issue":"1","key":"2026081411070376200_cit5","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1007\/s10565-025-10111-w","article-title":"Ferroptosis in liver\nfibrosis and\nits potential intervention strategy","volume":"41","author":"Zhu","year":"2025","journal-title":"Cell Biol.\nToxicol."},{"issue":"11","key":"2026081411070376200_cit6","doi-asserted-by":"publisher","first-page":"6109","DOI":"10.3390\/ijms22116109","article-title":"The Mechanism of Drug Nephrotoxicity and the Methods\nfor Preventing Kidney Damage","volume":"22","author":"Kwiatkowska","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"3","key":"2026081411070376200_cit7","doi-asserted-by":"publisher","first-page":"95","DOI":"10.4103\/japtr.JAPTR_336_18","article-title":"Nephrotoxicity: Role and significance of renal biomarkers\nin the early detection of acute renal injury","volume":"10","author":"Al-Naimi","year":"2019","journal-title":"J. Adv. Pharm. Technol. 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Inflammation Res."},{"issue":"9","key":"2026081411070376200_cit16","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1080\/15548627.2020.1810918","article-title":"Ferroptosis: machinery\nand regulation","volume":"17","author":"Chen","year":"2021","journal-title":"Autophagy"},{"issue":"1","key":"2026081411070376200_cit17","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41420-021-00579-w","article-title":"Ferroptosis:\na cell death connecting oxidative stress, inflammation and cardiovascular\ndiseases","volume":"7","author":"Yu","year":"2021","journal-title":"Cell Death Discov."},{"key":"2026081411070376200_cit18","doi-asserted-by":"publisher","first-page":"1726210","DOI":"10.3389\/fimmu.2025.1726210","article-title":"Iron-fueled ferroptosis: a new axis for immunomodulation to overcome\ncancer drug resistance-from immune microenvironment crosstalk to therapeutic\ntranslation","volume":"16","author":"Wu","year":"2026","journal-title":"Front. 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