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

AX5-159
Table AX5-10.1 (cont’d). Hepatic Drug Metabolism
Concentration Duration Species Blood Lead Effects a Reference
10–100 µM,
in vitro
5 and 10
µmoles/100 g of
b.wt, single i.p
100 µmoles/100 g
b. wt. Pb nitrate,
single injection, i.v.
100 mg/kg i.p.,
single exposure
100 µmol/kg body
wt, i.v
100 µmol/kg b. wt.,
intra cardiac
10 µmol/100g b.
wt., Pb nitrate, i.v.
single dose
24 h Murine
hepatoma cell
line
Animals were
sacrificed at
1, 2, 3, 4, and
15 days
— Effect of heavy metals on Aryl hydrocarbon regulated genes—
metals alone did not induce a significant change in the cyp1a1
activity and protein levels but increased its m-RNA expression.
AHR ligand-mediated induction of cyp1a1 activity and protein was
observed by all the metals. Pre and post translational modulation in
this regulation have been implicated. These results demonstrate
that the heavy metals differentially modulate the constitutive and
the inducible expression of AHR regulated genes.
— Wistar Rat — Pb nitrate induced the expression of Placental form of Glutathione
transferase along with liver cell proliferation. The biochemical
lesions induced by Pb under these conditions were similar to that of
hepatic nodules.
Multiple analyses
0–96 h
Wistar rats — Acute Pb treatment results in induced activity of Gamma-glutamyl
transpeptidase, induced GSTP, a typical marker of pre neoplastic
lesion in most hepatocytes. Pb also inhibited liver adenylate
cyclase activity 24 h postexposure.
Male DDY
strain mice
70 h Male Sprague
Dawley rats
Multiple time
point analyses
starting 6 days to
5 mo
Analyses at
multiple time
points 0–10 days
Male and
female Wistar
rats
Male Fischer
344 young adult
rats
— Pb decreased Glutathione content and decreased Glutathione stransferase
activity that is independent of Glutathione levels.
— Acute Pb nitrate treatment caused a significant increase of GST
activity in liver and kidney. While in liver the activity increase is
mainly due to isozyme GST 7-7, in kidney it is through the
induction of all the isozymes.
— Intracardiac administration of Pb acetate results in elevation of
glutathione transferase (GST) in Kupffer cells, the early response to
GST.Yp was observed in sinusoidal cells and had a later patchy
response in the expression of GST.Yp Yp in hepatocytes
— Glutathione transferase P1-1 is induced significantly by a single
intravenous dose of Pb nitrate through increased transcription and
modulations at post transcription and translational levels.
Korashy and
El-Kadi (2004)
Roomi et al.
(1987)
Columbano et al.
(1988)
Nakagawa et al.
(1991)
Planas-Bhone and
Elizalde (1992)
Boyce and Mantel
(1993)
Koo et al. (1994)