Inhibition of adriamycin cardiotoxicity by 5-fluorouracil: a potential free oxygen radical scavenger.
Adriamycin (ADR), a broad spectrum anticancer agent, has a limit to total dose used, due to cumulative cardiotoxicity. This side effect has been tested in the present study in combined administration with 5-fluorouracil a cytotoxic drug that often is applied together with ADR in cancer treatment. The study was performed on Wistar rats, and the experiment consisted of weekly administration for 12 weeks of adriamycin alone, of 5-fluorouracil alone, a combination of both, and a control group (normal saline) in separate groups comprising 42 animals each. The histology of the cardiac muscle, large vessels and liver, biochemistry of serum cholesterol, triglycerides and HDL-C and oxygen free radical production were examined. It was found that addition of 5-FU to the ADR administration reduced significantly the cardiac lesions, delayed and reduced the increase of serum lipids, produced by ADR alone and oxygen free radical production was also reduced, indicating that 5-fluorouracil is acting as a scavenger of free radicals.
Stathopoulos
G P
GP
Hippokration-Oncology Department, School of Medicine, University of Athens, Greece.
Malamos
N A
NA
Dontas
I
I
Deliconstantinos
G
G
Perrea-Kotsareli
D
D
Karayannacos
P E
PE
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
D008076:Cholesterol, HDL; D016166:Free Radical Scavengers; D005609:Free Radicals; D014280:Triglycerides; D004317:Doxorubicin; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005472:Fluorouracil