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

AX5-175
Table AX5-10.5 (cont’d). Lead-induced Liver Hyperplasia: Mediators and Molecular Mechanisms
Concentration Duration Species Blood Lead Effects a Reference
Multiple doses
0–50 µM, culture
medium
50 µM Pb acetate,
culture medium
10 µM/110 g b. wt.,
single i.v.
10 µmol/100 g b. wt.
single i.v.
10 mmol/100 g,
Pb nitrate, i.v.
Multiple time points
up to 24 h
Hepatocytes from
Adult male Swissmice,
primary
24 h Rat hepatocyte
and Kupffer cell
and granulocyte
co-cultures
Multiple time point
analyses up to
5 days
Multiple time points
up to 9 days
Adult male Wistar
rats
— Interaction between Pb and cytokines in hepatotoxicity– Pb potentiated
cytokine-induced oxidative stress by decreasing GSH and increased efflux
of Oxidized glutathione (GSSG). Combined treatment resulted in a
decline in intra cellular ATP concentration.
— Pb stimulates intercellular signaling between Kupffer cells and
hepatocytes which increased synergistically at low lipopolysaccharide
levels. These signals promote proteolytic hepatocyte killing in
combination with a direct cellular interaction between the granulocytes
and hepatocytes.
— Pb nitrate induced hepatocyte apoptosis was prevented by pre-treatment
with gadolinium chloride, a Kupffer cell toxicant—Role for Kuffer cell in
hepatocyte apoptosis.
Male Wistar rats — Pb nitrate-induced liver hyperplasia in rats results in a significant increase
in the expression of aceyl glycoprotein receptor (ASGP-R) during the
involutive phase of Pb nitrate induced hyperplasia in rat-liver, which
coincided with the massive death by apoptosis of the same cells.
A significant rise in the galactose-specific receptors was also observed
3 days after the treatment. These studies demonstrate that carbohydrate
receptors regulate Pb nitrate induced liver cell apoptosis.
Multiple time points Male Wistar rats — Demonstration of the expression of carbohydrate receptors on Kupffer
cells. Pb nitrate induced apoptosis in Kupffer cells and internalization of
apoptotic cells (Phagocytes) is mediated by both Mannose and Galactose
receptors.
Sieg and Billing
(1997)
Milosevic and
Maier (2000)
Pagliara et al.
(2003a)
Dini et al. (1993)
Ruzittu et al. (1999)