PMID- 11132608
OWN - NLM
STAT- MEDLINE
DCOM- 20010329
LR  - 20190822
IS  - 0263-6352 (Print)
IS  - 0263-6352 (Linking)
VI  - 18
IP  - 12
DP  - 2000 Dec
TI  - Phytoestrogens attenuate oxidative DNA damage in vascular smooth muscle cells 
      from stroke-prone spontaneously hypertensive rats.
PG  - 1833-40
AB  - OBJECTIVES: A recent study demonstrated that reactive oxygen species (ROS) were 
      involved in the maintenance of hypertension in stroke-prone spontaneously 
      hypertensive rats (SHRSP). However, the role of oxidative stress in hypertension 
      and its related diseases in SHRSP remains unknown. To determine whether 
      phytoestrogens attenuate oxidative DNA damage in vascular smooth muscle cells 
      (VSMC) from SHRSP and Wistar-Kyoto (WKY) rats, we investigated the effect of 
      daidzein, genistein and resveratrol on oxidative DNA damage in VSMC, induced by 
      advanced glycation end-products (AGEs). METHODS: VSMC were treated with AGEs in 
      the presence or absence of phytoestrogens for the indicated time. Cellular 
      degeneration induced by AGEs was characterized in terms of intracellular oxidant 
      levels, intracellular total glutathione (GSH) levels, mRNA expression for 
      gamma-glutamylcysteine synthetase (GCS), and a new marker of oxidative stress, 
      8-hydroxy-2'-deoxyguanosine (8-OHdG) contents. RESULTS: AGEs stimulated 8-OHdG 
      formation in VSMC in a time- and dose-dependent manner. We also confirmed that 
      VSMC from SHRSP were more vulnerable to oxidative stress induced by AGEs, than 
      VSMC from WKY rats. Daidzein, genistein or resveratrol reduced AGEs-induced 
      8-OHdG formation in a dose-dependent manner. The preventive effects of 
      phytoestrogens on 8-OHdG formation remarkably paralleled changes in the 
      intracellular oxidant levels in VSMC following AGEs treatment. We further 
      demonstrated that phytoestrogens increase intracellular total GSH level in VSMC. 
      Increased GSH synthesis was due to enhanced expression of the rate-limiting 
      enzyme for GSH synthesis, GCS. Phytoestrogens-stimulated total GSH level in VSMC 
      could lead to decreased intracellular oxidant levels, and thus prevent oxidative 
      DNA damage, induced by AGEs. The phytoestrogens are powerful antioxidants able to 
      interfere with AGEs-mediated oxidative DNA damage of VSMC, and are potentially 
      useful against vascular diseases where ROS are involved in hypertension.
FAU - Mizutani, K
AU  - Mizutani K
AD  - Life Science, Environmental Conservation and Development, Graduate School of 
      Human and Environmental Studies, Kyoto University, Japan. 
      mizutani@fischer.jinkan.kyoto-u.ac.jp
FAU - Ikeda, K
AU  - Ikeda K
FAU - Nishikata, T
AU  - Nishikata T
FAU - Yamori, Y
AU  - Yamori Y
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Hypertens
JT  - Journal of hypertension
JID - 8306882
RN  - 0 (DNA Primers)
RN  - 0 (Estrogens, Non-Steroidal)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Isoflavones)
RN  - 0 (Phytoestrogens)
RN  - 0 (Plant Preparations)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Stilbenes)
RN  - 6287WC5J2L (daidzein)
RN  - DH2M523P0H (Genistein)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - GAN16C9B8O (Glutathione)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cells, Cultured
MH  - *DNA Damage
MH  - DNA Primers/genetics
MH  - Estrogens, Non-Steroidal/*pharmacology
MH  - Genistein/pharmacology
MH  - Glutathione/metabolism
MH  - Glutathione Peroxidase/genetics/metabolism
MH  - Glycation End Products, Advanced/toxicity
MH  - Hypertension/etiology/*metabolism
MH  - Isoflavones/pharmacology
MH  - Muscle, Smooth, Vascular/*drug effects/*metabolism
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Phytoestrogens
MH  - Plant Preparations
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Reactive Oxygen Species/metabolism
MH  - Resveratrol
MH  - Stilbenes/pharmacology
MH  - Stroke/etiology/metabolism
EDAT- 2001/01/02 11:00
MHDA- 2001/04/03 10:01
CRDT- 2001/01/02 11:00
PHST- 2001/01/02 11:00 [pubmed]
PHST- 2001/04/03 10:01 [medline]
PHST- 2001/01/02 11:00 [entrez]
AID - 10.1097/00004872-200018120-00018 [doi]
PST - ppublish
SO  - J Hypertens. 2000 Dec;18(12):1833-40. doi: 10.1097/00004872-200018120-00018.