Cisplatin ranks among the most commonly employed chemotherapeutic agents. Certain lesser-recognized adverse effects, such as genetic toxicity, are associated with its extensive application. Kaempferol and quercetin represent two flavonoids known for their antioxidant capabilities. The purpose of this research was to examine cisplatin's genetic toxicity in human peripheral blood lymphocytes and to explore the potential safeguarding roles of quercetin and kaempferol. Lymphocytes were divided into several categories: a group exposed to cisplatin (0.8 µg/mL); group 1 treated with cisplatin (0.8 µg/mL) plus kaempferol (25 µM); group 2 treated with cisplatin (0.8 µg/mL) plus quercetin (25 µM); and a negative control group. Genetic damage was assessed via the alkaline single-cell gel electrophoresis (comet) assay and the cytokinesis-block micronucleus assay. Markers of oxidative stress, including glutathione levels, malondialdehyde content, superoxide dismutase activity, and catalase activity, were also determined. Findings indicated that cisplatin triggers oxidative stress through depletion of glutathione, reduced catalase and superoxide dismutase activities, and elevated lipid peroxidation. Genotoxicity tests revealed that cisplatin increased the frequency of micronuclei as well as the tail DNA percentage and tail moment in the comet assay. Both quercetin and kaempferol reduced the micronucleus frequency, tail DNA percentage, tail moment, and lipid peroxidation levels. Each compound enhanced superoxide dismutase activity; however, only quercetin markedly elevated glutathione levels and catalase activity relative to the cisplatin-exposed group. Oxidative stress appears to play a central role in the genetic toxicity caused by cisplatin. Additionally, quercetin or kaempferol supplementation could offer protection against cisplatin-related DNA damage in human peripheral blood lymphocytes.
