Doxorubicin (DOX) produces clinically restorative responses in numerous human
cancers, but its
cardiotoxicity has limited its usefulness. Because
reactive oxygen species may affect DOX-induced antitumor activity and
cardiotoxicity, we evaluated the prophylactic effect of spinach natural
antioxidant (
NAO) on DOX-induced
cardiotoxicity and oxidative stress in female Balb/c mice using histological, electron microscopical and biochemical parameters. Mice were treated with
NAO for 7 days prior to and/or for 6 days after DOX administration. Pretreatment with
NAO (cumulative dose: 130 mg/kg) did not hinder the effectiveness of DOX. Light and electron microscopy of DOX-treated heart revealed myocardial degeneration. When administered combined before and after DOX,
NAO conferred the most significant cardiac protection. The effects of
NAO on the lipid peroxidation product,
malondialdehyde, and on H2O2/ hydroperoxides were examined on day 6 following DOX administration; levels of both were elevated in DOX-treated mice, compared to control. Pretreatment with
NAO prevented these changes. Pretreatment with
NAO before DOX administration decreased
catalase and increased
superoxide dismutase activities compared to the DOX group. Our results suggest usage of
NAO in combination with DOX as a prophylactic strategy to protect heart muscle from DOX-induced cellular damage.