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

AX5-162
Table AX5-10.2. Biochemical and Molecular Perturbations in Lead-induced Liver Tissue
Concentration Duration Species Blood Lead Effects a Reference
Pb-diethyl
dithiocarbomate
complex, Pb (DTC) 2,
or Pb acetate 0.033–
10 µM
0.5–20 h Primary hepatocytes — Effect of interactions between Pb and diethyl dithiocarbomate (DTC) on the
enzyme δ amino levulinic acid dehydratase in primary hepatocytes.
Lipophilic Pb (DTC)2 caused a more rapid and stronger inhibition of ALAD
activity than Pb acetate. Pb uptake is higher and more rapid with Pb (DTC)
2 than Pb acetate. This increased inhibition of ALAD activity by Pb (DTC)
2 might be due to facilitated cellular transport in the complexed form
resulting in higher cellular concentrations of Pb.
— — Primary rat
hepatocytes
— DTC decreases cellular effects of Pb and Cd despite unchanged/ even
slightly increased concentrations of the metals. Hepatic ALAD was
significantly inhibited in cells treated with Pb Ac and Pb (DTC)2.
— — DBA and C57 mice — DBA mice(with a duplication of the ALAD gene accumulated twice the
amount of Pb in their blood and had higher Pb levels in liver and kidney
than mice with the single copy of the gene (C57), exposed to the same oral
doses of the Pb during adult hood. Blood Zinc protoporphyrin (ZPP)
increased with Pb exposure in C57 mice and were not affected in DBA
mice.
100 µmol/kg b. wt.
i.v. single dose
Pb nitrate, Single dose
100 µmol/kg b. wt.
Single dose,
analyses performed
12, 24, 48, 72, 96
and 168 h
Male Wistar Albino
Rats
— First in vivo report showing association between Pb induced liver
hyperplasia, Glucose-6-phosphate levels, and cholesterol synthesis.
Pb treatment increased hepatic de novo synthesis of cholesterol as evident
by increased cholesterol esters and increase of G-6-PD to possibly supply
the reduced equivalents for de novo synthesis of cholesterol. Changes in
these biochemical parameters were accompanied by liver hyperplasia.
0–168 h Male Wistar rats — Pb nitrate induces hepatic cell proliferation followed by reabsorption of
excess tissue with in 10–14 days. The proliferation was correlated with
hepatic denovo synthesis of cholesterol, stimulation of hexose
monophosphate shunt pathway and alterations in serum lipo proteins.
Pb nitrate — Wistar rats — Pb nitrate induces multiple molecular forms of Glucose-6- phosphate
dehydrogenase with an increase of band 3 and a concomitant increase of
band 1, shifting from the pattern induced by fasting with an increase in
band 1.
Oskarsson and
Hellström-Lindahl
(1989)
Hellström-Lindahl
and Oskarsson
(1990)
Claudio et al.
(1997)
Dessi et al. (1984)
Pani et al. (1984)
Batetta et al. (1990)