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

AX5-163
Table AX5-10.2 (cont’d). Biochemical and Molecular Perturbations in Lead-induced Liver Tissue
Concentration Duration Species Blood Lead Effects a Reference
Pb nitrate, single i.v.
10 µM/100 g b. wt.
Multiple time points
24–72 h and
20 days
Male Wistar rats — Pb nitrate exposure results in complete loss of liver glycogen between 24
and 48 h, which was replenished and was found in excess in treated liver
hepatocytes by 20 days. Glycogen synthase and glycogen phosphorylase
activities were diminished by 24 h and return to normal values by day 20.
The pentose phosphate enzymes were upregulated, which coincided highly
with the increase in mitotic rate. Overall Pb nitrate induces drastic
alterations in hepatic carbohydrate metabolism along with increased hepatic
cell proliferation.
— — Rats — Pb acetate induced mitotic response much more effectively in renal
epithelial cells than liver cells (675 fold less).
10 or 20 mg/kg as Pb
acetate, subcutaneous
100 µM/kg b. wt Pb
nitrate, i.v
2000 ppm Pb acetate
in diet.
0–4000 ppm
Pb acetate, oral
Once a wk for
5 wks
Occupationally
exposed workers
Rats
36 h postexposure Male Wistar Albino
rats
3 wks Arbor Acres male
chicks
21 days Arbor Acre broiler
chicks
Pb-exposed
workers:
0.24–30 nM/mL
Control rats:
0.18 nM/mL
10 mg Pb/kg:
2.42 nM/mL:
20 mg Pb/kg:
3.82 nM/mL
Pb induces lipid peroxidation in serum of manual workers, while blood
superoxide dismutase (SOD) activity decreased. Similar phenomenon was
observed with rats that were subcutaneously injected with Pb acetate.
At higher than 20 µM concentration, Pb in untreated microsomes increased
NADPH dependent lipid peroxidation.
— Endogenous source of newly synthesized cholesterol together with increase
of HMP shunt enzyme activities is essential for hepatic cell proliferation by
Pb nitrate.
— Liver non protein sulphahydryl (NPSH) and glutathione (GSH) were
increased upon Pb exposure. The concentrations of liver glutamate, glycine,
and methionine were also elevated upon Pb exposure.
— Pb increases tissue peroxidation via a relative increase of 20:4 fatty acids.
Decrease in the hepatic ratio of 18:2/20:4 might be specific to Pb toxicity.
Hacker et al. (1990)
Calabrese and
Baldwin et al.
(1992)
Ito et al. (1985)
Dessi et al. (1990)
Mc Gowan and
Donaldson et al.
(1987)
Donald and
Leeming (1984)