Coffee increases levels of urinary 8-hydroxydeoxyguanosine in rats.
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.
Sakamoto
Wataru
W
Department of Biochemistry, School of Dentistry, Hokkaido University, Sapporo 060, Japan. sakamoto@den.hokudai.ac.jp
Isomura
Haruo
H
Fujie
Katsutoshi
K
Nishihira
Jun
J
Ozaki
Mitsuru
M
Yukawa
Susumu
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001835:Body Weight; D002726:Chlorogenic Acid / Q000378:metabolism*; D003069:Coffee / Q000378:metabolism / Q000633:toxicity*; D003300:Copper / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D004249:DNA Damage; D003849:Deoxyguanosine / Q000819:agonists / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000652:urine*; D006801:Humans; D028421:Isoprostanes / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D003069:Coffee; D028421:Isoprostanes; D002726:Chlorogenic Acid; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003404:Creatinine; C028419:cuprous chloride; D003849:Deoxyguanosine