ARTICLES Improvement of the Therapeutic Index of Anticancer Drugs by the Superoxide Dismutase Mimic Mangafodipir

Background: Anticancer drugs act by increasing intracellular hydrogen peroxide levels. Mangafodipir, a superoxide dis-mutase (SOD) mimic with catalase and glutathione reductase activities, protects normal cells from apoptosis induced by H 2 O 2. We investigated its and other oxidative stress modula-tors ’ effects on anticancer drug activity in vitro and in vivo. Methods: Cell lysis and intracellular reactive oxygen species levels were assessed in vitro in human leukocytes from healthy subjects and in murine CT26 colon cancer cells. Cells were exposed to the chemotherapeutic agents paclitaxel, oxalipla-tin, or 5-fl uorouracil, either in the presence or absence of mangafodipir and other oxidative stress modulators. Cell viability was evaluated by the methylthiazoletetrazolium assay. The effects of mangafodipir and other oxidative stress modulators on peripheral blood counts and on tumor growt