Atorvastatin Mitigates Cisplatin-induced Genotoxicity and Oxidative Stress in Human Lymphocytes: Insights From the Micronucleus Assay

Background: 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.  Objectives: This study aimed to evaluate the protective potential of atorvastatin (Atv) against Cis-induced genotoxicity in cultured human lymphocytes. Methods: Peripheral lymphocytes were divided into four groups: control, Cis (۱۲ μM), Atv combined with Cis (۵۰, ۱۰۰, ۱۰۰۰ μM), and Atv alone (۱۰۰۰ μM). 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. Results: Cis treatment significantly increased MN frequency and LPO levels and reduced GSH compared with the control group (P<۰.۰۵). 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 ۵۰ μM Atv, consistent with a hormetic antioxidant response. Higher concentrations (۱۰۰–۱۰۰۰ μM) did not further enhance antioxidant effects, likely due to saturation of cellular uptake or mild redox imbalance. Conclusion: 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.

کلیدواژه ها:

Cisplatin (Cis) ، Genotoxicity ، Lymphocytes ، Atorvastatin (Atv) ، Micronucleus (MN) test ، Oxidative stress