Doxorubicin as an antioxidant: maintenance of myocardial levels of lycopene under doxorubicin treatment.
The mechanism of doxorubicin-induced cardiotoxicity remains controversial. Wistar rats (n=96) were randomly assigned to a control (C), lycopene (L), doxorubicin (D), or doxorubicin+lycopene (DL) group. The L and DL groups received lycopene (5 mg/kg body wt/day by gavage) for 7 weeks. The D and DL groups received doxorubicin (4 mg/kg body wt intraperitoneally) at 3, 4, 5, and 6 weeks and were killed at 7 weeks for analyses. Myocardial tissue lycopene levels and total antioxidant performance (TAP) were analyzed by HPLC and fluorometry, respectively. Lycopene metabolism was determined by incubating (2)H(10)-lycopene with intestinal mucosa postmitochondrial fraction and lipoxygenase and analyzed with HPLC and APCI mass spectroscopy. Myocardial tissue lycopene levels in DL and L were similar. TAP adjusted for tissue protein were higher in myocardium of D than those of C (P=0.002). Lycopene metabolism study identified a lower oxidative cleavage of lycopene in D as compared to those of C. Our results showed that lycopene was not depleted in myocardium of lycopene-supplemented rats treated with doxorubicin and that higher antioxidant capacity in myocardium and less oxidative cleavage of lycopene in intestinal mucosa of doxorubicin-treated rats suggest an antioxidant role of doxorubicin rather than acting as a prooxidant.
Department of Internal Medicine, Botucatu Faculty of Medicine, UNESP, São Paulo State University, CEP: 18618-970, Botucatu, SP, Brazil. ferreira@fmb.unesp.br
Ana Lucia Anjos
AL
Ferreira
Kyung-Jin
KJ
Yeum
Luiz Shiguero
LS
Matsubara
Beatriz Bojikian
BB
Matsubara
Camila R
CR
Correa
Elenize Jamas
EJ
Pereira
Robert Mitchell
RM
Russell
Norman I
NI
Krinsky
Guangwen
G
Tang
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002338:Carotenoids / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D002384:Catalysis; D002853:Chromatography, Liquid; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007700:Kinetics; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D009206:Myocardium / Q000378:metabolism*; D009827:Oleandomycin / Q000493:pharmacokinetics; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013752:Tetracycline / Q000493:pharmacokinetics
D000975:Antioxidants; D002338:Carotenoids; D004317:Doxorubicin; C013170:oletetrin; D013752:Tetracycline; D009827:Oleandomycin; D000077276:Lycopene