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

AX5-165
Table AX5-10.3. Effect of Lead Exposure on Hepatic Cholesterol Metabolism
Concentration Duration Species Blood Lead Effects a Reference
100 µmol/kg body wt,
i.v. Pb nitrate
100 µmol/kg body wt,
i.v. Pb nitrate
0.05 mg/kg body
wt/d. Pb acetate,
subcutaneous, with or
without cadmium
acetate 0.025 mg Pb
acetate/kg body wt/d
300 mg/L Pb acetate,
oral
a CYP—Cytochrome P-450
b wt.—body weight
Multiple durations
0, 3, 6, 12, 24, and
48 h
Multiple durations
0, 1, 3, 6, 12, 18, 24,
48, and 72 h
Preexposure for
5–7 days, gestation
through lactation
Gestation through
lactation analyses
done at day 12 and
day 21 postnatal
Male Sprague
Dwaley (SD) rats
Male Sprague
Dawley (SD) rats
Female Charles
Foster rats
Female Wistar
rats
— Pb nitrate, activates the expression of the SREBP-2 and CYP 51 gene
with out decreasing the serum cholesterol level.
— Pb nitrate effects on hepatic enzymes involved in cholesterol homeostasis.
Demonstrated for the first time sterol independent gene regulation of
cholesterol synthesis in Pb nitrate treatment.
— Pb and cadmium accumulated in the livers of metal treated pregnant and
lactating rats. Hepatic steroid metabolizing enzyme 17-β-hydroxy steroid
oxidoreductase and UDP glucaronyl transferase were decreased and the
hepatic Cytochrome P-450 content was reduced by the metal exposure.
Pb and cadmium alter liver biochemical parameters, however, combined
exposure had no intensifying effect on liver parameters. When
administered together on similar concentration basis, the major effects
are mediated by cadmium.
Control: 1.13 µg/dL
Pb-exposed
12 days PN: 22.01
µg/dL
21d PN: 22.77 µg/dL
In neonates, decrease in liver Hb, iron, alkaline and acid phosphatase
levels. Protein, DNA and lipid total amounts were reduced and hepatic
glycogen content was reduced. Pb intoxication of mothers in gestation
and lactation results in alterations in the hepatic system in neonates
and pups.
Kojima et al. (2002)
Kojima et al. (2004)
Pillai and Gupta
(2004)
Corpas et al.
(2002b)