Effect of vitamin C supplementation on oxidative DNA damage in an experimental model of lead-induced hypertension.
OBJECTIVE
Chronic exposure to lead results in sustained hypertension in humans and experimental animals. We investigated the possible role of reactive oxygen species (ROS) and their impact on DNA damage in lead-induced hypertension. Further the effect of short-term supplementation of vitamin C is also demonstrated.


METHODS
Male Wistar rats were treated with either lead acetate (100 ppm) alone or lead acetate plus vitamin C (20 mg/rat/day). The control rats were fed regular rat chow. Blood pressure, antioxidants, total antioxidant status as measured by ferric-reducing antioxidant power, nitric oxide (NO) metabolites, malondialdehyde (MDA) and 8-hydroxy 2-deoxyguanosine were determined after 0, 1, 2 and 3 months.


RESULTS
The lead-exposed group showed a significant rise in blood pressure, lipid peroxidation (MDA) and a substantial oxidative damage to the DNA. A significant fall in NO metabolites, total antioxidant levels and ferric-reducing antioxidant power was also observed in this group. Concomitant administration of vitamin C ameliorated hypertension, normalized NO levels and abrogated lipid peroxidation. Also, it completely prevented oxidative damage to the DNA.


CONCLUSIONS
These findings point to enhanced ROS-mediated inactivation and sequestration of NO which can potentially contribute to hypertension, lipid peroxidation, reduced antioxidant status and oxidative DNA damage. The beneficial effects of vitamin C on these parameters support the role of increased ROS activity in the pathogenesis of these abnormalities in this model.
Attri
Jyotika
J
Department of Experimental Medicine and Biotechnology, and Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Dhawan
Veena
V
Mahmood
Safrun
S
Pandhi
Promila
P
Parwana
H K
HK
Nath
Ravinder
R
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D003839:Deoxyadenosines / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007855:Lead Poisoning / Q000150:complications; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity; D010084:Oxidation-Reduction; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors
C436623:8-hydroxy-2'-deoxyadenosine; D000975:Antioxidants; D003839:Deoxyadenosines; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D008315:Malondialdehyde; D001205:Ascorbic Acid; C008261:lead acetate