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

AX5-168
Table AX5-10.4 (cont’d). Lead, Oxidative Stress, and Chelation Therapy
Concentration and
Compound Duration Species Blood Lead Effects Reference
20 mg/kg Pb acetate,
i.p.
3 days treatment Male Albino rats — Significant Pb induced inhibition of hepatic heme synthesis associated
with decline of mixed function oxidases, depletion in anti oxidants such
as vitamin C. Oral supplementation with vitamin C confers protection
against toxic insult by reversing these parameters.
1.5 mg/per bird /d 30 days Broiler chicken — Pb-induced inhibition of 5' mono deiodinase (5'- D) activity in chickens
appeared to be mediated through the lipid peroxidative process.
1. Pb acetate
10 mg/mL/kg (a)
2. Ethanol 1 g/
4 mL/kg (b)
3. a + b = (c)
4 a + zinc 10 mg/
4 mL/kg + lysine
25 mg/4 mL/kg
(d)
5. b + 2n + lysine as
in days, oral
6. a + b + Zn +
lysine as in days
1300 ppm Pb acetate
in drinking water
2000 ppm of Pb
acetate in drinking
water
500 µM Pb acetate in
cells
2000 ppm of Pb
acetate in drinking
water
5 days/wk/8 wk Male Albino rats Control: 1.75 µg/dL
1. 47.23 µg/dL
2. 2.08 µg/dL
3. 45.37 µg/dL
4. 34.19 µg/dL
5. 1.84 µg/dL
6. 46.69 µg/dL
Influence of lysine and zinc administration on the Pb-sensitive
biochemical parameters and the accumulation of Pb during exposure to
Pb. (1) Pb exposure inhibited blood ALAD activity. Serum enzymes
increased blood and tissue Pb levels. (2) Decreased blood and hepatic
glutathione. Some of these effects were enhanced with co-exposure to
ethanol. Simultaneous administration of lysine and zinc reduced tissue
accumulation of Pb and most of the Pb-induced biochemical alterations
irrespective of exposure to Pb alone or Pb and ethanol.
5 wks C57BL/6 mice — Pb treatment resulted in depletion of GSH, increased GSSG and promoted
Malondialdehyde (MDA) production in both liver and brain samples.
DMSA or N- acetyl cysteine (NAC) treatment resulted in reversion of
these observations. DMSA treatment resulted in reduced Pb levels in
blood, liver and brain, where as treatment with NAC did not reduce these
levels.
5 wks followed by
treatment with
succimer DMSA, or
thiol agent NAC
Cells—20 h
Animals 5 wks
followed by
treatment with
α-lipoic acid
Fisher 344 male
rats
Male fisher rats
and Chinese
hamster ovary
cells
— Pb induces oxidative stress in RBC and these biochemical alterations are
reversed by both a thiol antioxidant (NAC) as well as a chelating agent
DMSA.
— Pb induces oxidative stress. α-lipoic acid (LA)treatment significantly
increased thiol capacity of cells and animals via increasing glutathione
levels and reducing Malondialdehyde levels, increased cell survival.
LA was not effective against reducing blood or tissue Pb levels.
Vij et al. (1998)
Chaurasia et al.
(1998)
Tandon et al. (1997)
Ercal (1996)
Gurer et al. (1998)
Gurer et al. (1999)