E. Breitbart et al., Effects of water-soluble antioxidant from spinach, NAO, on doxorubicin-induced heart injury, HUM EXP TOX, 20(7), 2001, pp. 337-345
Doxorubicin (DOX) produces clinically restorative responses innumerous huma
n cancers, butits cardiotoxicity has limited its usefulness. Because reacti
ve oxygen species may affect DOX-induced antitumor activity and cardiotoxic
ity, we evaluated the prophylactic effect of spinach natural antioxidant (N
AO) on DOX-induced cardiotoxicity and oxidative stress in female Balb/c mic
e using histological, electron microscopical and biochemical parameters. Mi
ce were treated with NAO for 7 days prior to and/or for 6 days after DOX ad
ministration. Pretreatment with NAO (cumulative dose: 130 mg/kg) did not hi
nder 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 e
ffects of NAO on the lipid peroxidation product, malondialdehyde, and on H2
O2/hydroperoxides were examined on day 6 following DOX administration; leve
ls of both were elevated in DOX-treated mice, compared to control. Pretreat
ment with NAO prevented these changes. Pretreatment with NAO before DOX adm
inistration decreased catalase and increased superoxide dismutase activitie
s compared to the DOX group. Our results suggest usage of NAO in combinatio
n with DOX as a prophylactic strategy to protect heart muscle from DOX-indu
ced cellular damage.