en سم شناسی Toxicology پژوهشي Original Research <strong>&nbsp;Background: </strong>Cisplatin (Cis), an alkylating antineoplastic agent, is commonly used to treat bladder, ovarian, and testicular cancers. Prolonged use can lead to genotoxicity, potentially mediated by oxidative stress.&nbsp;<br> <strong>Objectives</strong>: This study aimed to evaluate the protective potential of atorvastatin (Atv) against Cis-induced genotoxicity in cultured human lymphocytes.<br> <strong>Methods</strong>: Peripheral lymphocytes were divided into four groups: control, Cis (12 &mu;M), Atv combined with Cis (50, 100, 1000 &mu;M), and Atv alone (1000 &mu;M). Micronucleus (MN) frequency was assessed as a marker of chromosomal damage, while glutathione (GSH) levels and lipid peroxidation (LPO) were measured to evaluate oxidative stress.<br> <strong>Results</strong>: Cis treatment significantly increased MN frequency and LPO levels and reduced GSH compared with the control group (P<0.05). Co-treatment with Atv markedly ameliorated MN formation and oxidative stress markers, restoring GSH levels toward baseline. Notably, the protective effect was most pronounced at 50 &mu;M Atv, consistent with a hormetic antioxidant response. Higher concentrations (100&ndash;1000 &mu;M) did not further enhance antioxidant effects, likely due to saturation of cellular uptake or mild redox imbalance.<br> <strong>Conclusion</strong>: Cis induces genotoxicity in human lymphocytes primarily through oxidative stress mechanisms. Atv effectively mitigates this genotoxicity by restoring redox homeostasis and enhancing chromosomal protection, with an optimal protective effect observed at intermediate concentrations. These findings suggest that Atv may have therapeutic potential to counteract Cis-induced cellular damage and support further investigation into its adjunctive use in chemotherapy. Cisplatin (Cis), Genotoxicity, Lymphocytes, Atorvastatin (Atv), Micronucleus (MN) test, Oxidative stress 27 36 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-48-7&slc_lang=en&sid=1 Mohammad Shokrzadeh mslamuk@yahoo.com 100319475328460012023 100319475328460012023 No Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran. Mona Modanloo dr_modanloo@yahoo.com 100319475328460012024 100319475328460012024 No Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Mina Fasihbeiki mina.fasih5726@gmail.com 100319475328460012025 100319475328460012025 No Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran. Ehsan Zamani shadigholampour97@gmail.com 100319475328460012026 100319475328460012026 No Department of Pharmacology and Toxicology, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran. Mona Alinia monaaliniiia@gmail.com 100319475328460012027 0009-0001-6696-8909 No Department of Pharmacology and Toxicology, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran. Fatemeh Shaki fshaki.tox@gmail.com 100319475328460012028 100319475328460012028 Yes Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.