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Effects of water-soluble antioxidant from spinach, NAO, on doxorubicin-induced heart injury

L Lomnitski

Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel

A Nyska

National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, Israel

Z Malik

M Bergman

Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel

Y Sofer

The College of Judea and Samaria, Ariel, Israel

J K Haseman

National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, Israel

S Grossman

Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel

Doxorubicin (DOX) produces clinically restorative responsesinnumeroushumancancers,butitscardiotoxicity has limited its usefulness. Because reactive oxygen species may affect DOX-induced antitumor activity and cardiotoxicity, weevaluated the prophylactic effect ofspinachnatural 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 significantcardiacprotection.TheeffectsofNAOonthelipid 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 super oxide 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 inducedcellulardamage.

Key Words: antioxidants • cardiotoxicity • doxorubicin • oxidative stress • polyphenols

Human & Experimental Toxicology, Vol. 20, No. 7, 337-345 (2001)
DOI: 10.1191/096032701680350604


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