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Protective effect of carotenoids on lipid peroxidation, oxidative damage to DNA histological lesions induced by iron

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Author(s):
Humberto Reis Matos
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
Defense date:
Examining board members:
Marisa Helena Gennari de Medeiros; Etelvino Jose Henriques Bechara; Ana Campa; Rui Curi; Elizabeth Angelica Leme Martins; Ana Lucia Tabet Oller do Nascimento
Advisor: Marisa Helena Gennari de Medeiros
Abstract

Experimental and epidemiological evidences suggest that lycopene and β-carotene, carotenoids present in tomatoes, tomato products and several fruits and vegetables may play a role in preventing certain cancers in humans. However, to establish their role in health, more information is required to identify the biochemical mechanisms associated with these processes. With the aim of producing such information, we have first investigated the effect of lycopene on lipid peroxidation and on the formation of 8-oxo-7,8-dihydro-2\'-deoxyguanosine (8-oxodGuo) in CV1-P monkey cells exposed to ferric nitrilotriacetate (Fe-NTA) plus ascorbate. Cells supplemented with lycopene (20 fmol/106 cells) showed an approximate reduction of 80% in Fe-NTA/ascorbate-induced lipid peroxidation (TBARS). Levels of 8-oxodGuo in the cells increased over tenfold after treatment with Fe-NTA/ascorbate as compared to the control group. Lycopene supplementation decreased 8-oxodGuo in Fe-NTA/ascorbate-treated cells to approximately 70%. In arder to verify if these effects are also operative in vivo, we have investigated the effect of lycopene and β-carotene pre-treatment on lipid peroxidation, oxidative damage to DNA and histopathological changes in liver, kidney, lung, prostate and Iymphocytes of animais subjected to i.p. ferric nitrilotriacetate (Fe-NTA) administration. Compared with control rats, liver of Fe-NTA treated animais showed a 2-5 fold increase in 8-oxodGuo level and 40-75 % increase in malodialdehyde (MDA) accumulation concomitant with tissue histopathological changes. Five days of lycopene and β-carotene pre-treatment (10 mg/kg body weight, i.p.) almost completely prevented liver biomolecule oxidative damage and protected the tissue against the observed histological alterations. In conclusion, it is shown that lycopene and β-carotene prevented oxidative damage to DNA, membranes and markedly reduced the histological changes induced by Fe-NTA. Inhibition of these oxidative processes by carotenoids is likely due to their ability to trap peroxyl radical and to quench singlet oxygen. The results described herein may contribute toward a better understanding of the biological mechanisms associated with the potential cancer-preventing property of carotenoids observed in epidemiological studies. (AU)