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Toxicology ; 183(1-3): 255-63, 2003 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-12504356

RESUMO

We examined whether coffee or chlorogenic acid inhibits 8-hydroxydeoxyguanosine (8-OHdG), one of the major forms of oxidative DNA damage, in vivo and in vitro. Forty-eight male Wistar rats were assigned to three treatment groups: a control-diet group (n=16; coffee-free diet), a 0.62% coffee-diet group (n=16, dose of coffee consumed 125 mg/day), and a 1.36% coffee-diet group (n=16, dose of coffee consumed 275 mg/day) and were maintained on an experimental diet for 130 days. The coffee-diet resulted in significantly increased excretion of urinary chlorogenic acid, with the 0.62 and 1.36% coffee-diets resulting in 14.00+/-0.94 and 15.80+/-0.41 ng/mg creatinine, respectively, whereas in control rats it was not detected. Using monoclonal antibody to measure 8-OHdG, it was revealed that coffee led to a significant increase in excretion of urinary 8-OHdG on day 130 (46.62+/-13.42 ng/mg creatinine in 0.62% coffee-diet group and 64.58+/-20.15 ng/mg creatinine in 1.36% coffee-diet group, P<0.05 vs. control; control group 10.89+/-2.59 ng/mg creatinine). Furthermore, to clarify the mechanism of 8-OHdG formation by coffee, we investigated the in vitro effect of chlorogenic acid on 8-OHdG formation in human placental DNA. Chlorogenic acid alone did not lead to an increase of 8-OHdG formation, but dramatically increased it in the presence of cupric chloride and H(2)O(2). However, chlorogenic acid and cupric chloride decreased the formation of 8-OHdG in the presence of H(2)O(2). Based on these results, a possible mechanism of 8-OHdG formation in vivo by chlorogenic acid is discussed.


Assuntos
Ácido Clorogênico/metabolismo , Café/toxicidade , Desoxiguanosina/análogos & derivados , Desoxiguanosina/biossíntese , Desoxiguanosina/urina , 8-Hidroxi-2'-Desoxiguanosina , Animais , Peso Corporal , Café/metabolismo , Cobre/metabolismo , Creatinina/urina , Dano ao DNA , Desoxiguanosina/agonistas , Humanos , Isoprostanos/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
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