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

AX5-158
Table AX5-10.1 (cont’d). Hepatic Drug Metabolism
Concentration Duration Species Blood Lead Effects a Reference
Single 0.33 mg/kg-
1 Pb nitrate
Pb acetate, 75 mg
of Pb 2+ /kg,
intraperitonial
Multiple
durations
Multiple analyses
up to 30 h
Male Wistar rats — Pb confers protection against the CCL4 induced hepatotoxicity as
evident by marked reduction in serum Alanine aminotransferase
(AST) and aspartate aminotransferase (AST) and this protection is
not associated with the mitotic response of Pb.
C57BL/6 male
mice
0–10 !6 M Pb nitrate 3 days Fish hepatoma
cell line
PLHC-1
DT Diaphorase
activity 0–125
mg/kg Pb acetate,
Pb nitrate
Time course
experiments
100 mg/kg Pb
acetate, i.p.
Cell viability
assays 0–30 µM,
for all other As ,
Pb, Hg, 5 µM, Cd,
1 µM
— The decrease in P-450 as a result of Pb poisoning occurs at two
levels. (1) A mechanism unrelated to heme, where Pb interferes
with P-450 in 2 ways. (2) A mechanism dependent on heme, in
which Pb inhibits heme synthesis.
— Effect of heavy metals Cu(II), Cd(II), Co(II), Ni(II), Pb(II), and
Zn(II), on Cytochrome induction (CYP1A) induction response and
Ethoxy resorufin-o-deethylase (EROD) activity.
All metals had a more pronounced effect on EROD activity than
Cyp1 A protein. The rank order of the metal inhibition on EROD is
Cd(II) > Ni(II) > Cu(II) > Co(II) = Zn(II), Pb(II), Cd(II) and (Cu).
May affect Cyp1 A system of the fish liver at low concentrations
through the direct inhibition of CYP 1A enzyme activity.
24 h–120 h Male Wistar rats — Pb acetate and nitrate induce DT diaphorase activity which is
inhibited significantly by Dil a calcium antagonist, showing that
these changes are mediated by intracellular calcium changes. Pb
acetate induces DT diaphorase activity with out thymus atrophy and
hence was suggested to be a monofunctional inducer as against the
Methyl cholanthrene induced DT diaphorase activity.
24 h in general
and for EROD
assays by PAHs
24–72 h
Primary human
hepatocytes
— The effect of metals on PAH induced CYP1A and 1A2 as probed
by Ethoxy resorufin o- deethylase activity has demonstrated, metals
-Arsenic, Pb, mercury and cadmium decreased CYP1A1/ A2
expression by polycyclic aromatic hydrocarbons depending on the
dose, metal and the PAH. Arsenic was most effective, followed by
Pb, cadmium, and mercury. Cell viability was decreased by 20–
28% by metals.
Calabrese et al.
(1995)
Jover (1996)
Bruschweiler
et al. (1996)
Arizono et al.
(1996)
Vakharia (2001)