Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

AX5-63
Table AX5-5.1 (cont’d). In Vivo and In Vitro Studies of the Effects of Lead Exposure on Production and Metabolism of
Reactive Oxygen Species, Nitric Oxide, and Soluble Guanylate Cyclease
Reference
Vaziri et al.
(1999a)
Vaziri et al.
(2003)
Ni et al.
(2004)
Pb Exposure Measured Parameters
Species/
Tissue Age/Weight n Dosage Duration Pb Level CVS Other Interventions Results
Male SD rats 200 g 6 per group 100 ppm in
water
Male SD rats 200 g 6 per group 100 ppm in
water
Cultured
human
coronary
endothelial and
VSM cells.
N/A $4 per
experiment
0,1 and 10
ppm Pb
acetate
3 mo 8.3–10.8 µg/g
kidney tissue
BP Urine NO2 +
NO3, tissue and
plasma
nitrotyrosine
(marker of
NO-ROS
interaction).
3 mo N/A BP Urine NO2 +
NO3, kidney,
heart, brain
SOD, catalase,
GPX, NAD(P)H
oxidase
abundance
Short
exposure
(5–30 min)
and long
exposure
(60 hr)
0, 1, 10 ppm N/A
•
O2 and H2O2
productions
SOD, catalase,
GPX and
NAD(P)H
oxidase
(gp91 phox )
Antioxidant Rx
(Vit E)
•
Tempol (O2
scavenger
infusion)
Pb exposure raised BP,
reduced Ur NO2 + NO3
and increased
nitrotyrosine abundance
in plasma, heart, kidney,
brain and liver. Anti ox
Rx ameliorated HTN,
lowered nitrotyrosine and
raised Ur NO2 + NO3.
Pb caused HTN,
↑NAD(P)H oxidase
(gp91 phox ), ↑SOD, unchanged
catalase and
GPX, ↓UrNO2 + NO3.
Tempol resulted in ↓BP
+ ↑urine NO2 + NO3 in
Pb-exposed but not
control rats.
None Short-term incubation
with Pb at 1 and 10 ppm
•
raised O2 and H2O2
productions by both
endothelial and VSM
cells, long-term
incubation resulted in
further rise in H2O2
generation and
normalization of
detectable O2y
• . This was
associated with increases
in NAD(P)H oxidase and
SOD and reduced or
unchanged catalase and
GPX.