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

AX5-170
Table AX5-10.4 (cont’d). Lead, Oxidative Stress, and Chelation Therapy
Concentration and
Compound Duration Species Blood Lead Effects Reference
2000 ppm Pb acetate,
oral
I chelators
LA, DMSA,
MiADMSA
LA + DMSA + LA+
MiADMSA
0.1% Pb as acetate in
drinking water
DMSA—50 mg/kg,
i.p./d
MiADMSA—50
mg/kg, i.p./d
Vitamin E 5 mg/kg
and vitamin C
25 mg/kg/d, i.v. and
oral
500 mg/kg Pb acetate
daily, oral treatment
with chelators
Pb as acetate 0.2% in
drinking water
LA 25 mg/kg b.wt and
DMSA 20 mg/kg b.wt
Abbreviations
4 wks, 5 days of
treatment with
antioxidant or
chelators
Male Wistar
albino rats
Normal: 1.42 µg/dL
Pb: 40.93 µg/dL
Pb + chelators: 38.5–
4.27 µg/dL
3 mo Male Wistar rats
—
5 days post-Pb
exposure
Multiple durations
(2, 4, and 6 wks)
5 wks followed by
a 6th wk
administration of
LA and or DMSA
b. wt.—body weight
a CYP—Cytochrome P-450
SOD—Super oxide dismutase
GSH—Glutathione
GSH/GSSG Ratio—Reduced Glutathione/Oxidized Glutathione
MDA—Malondialdehyde
Al—Aluminum
As—Arsenic
MiDMSA—Mi monoisoamyl DMSA
—
Male Albino rats Control: 0.32 µg/dL
Pb-exposed:
0.48–0.56 µg/dL
Pb + chelators:
0.32–0.36 µg/dL
Treatment with all the chelators reduced hepatic GSH and reduced GSSG
levels. Significant beneficial role of Alpha-lipoic acid (LA), in recovering
the altered biochemical parameters, however showed no chelating
properties in lessening body Pb burden either from blood, liver, or kidney.
Most beneficial effects against Pb poisoning was observed with combined
treatment of lipoic acid and either DMSA (meso 2,3-dimercaptosuccinic
acid) or MiADMSA (Mono isoamyl DMSA).
Single or combined administration of vitamin C, α-tocopherol and the
chelators DMSA and Mi ADMSA against the Parameters of Pb induced
oxidative stress– thiol chelators and the vitamins could bring the blood
ALAD to normal levels, most significantly by combined administration of
Mi ADMSA with vitamin C. Vitamin C and E were effective against
reducing oxidized glutathione ( GSSG), and thibarbituric acid reactive
substance(TBARS) and increasing catalase activity. MiADMSA and
DMSA with vitamin C were effective in increasing hepatic GSH levels.
In summary combined treatment regimens with thiol chelators and
vitamins seem very effective in reducing the Pb induced oxidative stress.
Impact of combined administration of vitamin C and Sylimarin on Pb
toxicity. Combined treatment of Pb-exposed animals with vitamin C and
Silymarin showed marked improvement of the adverse biochemical,
molecular and histopathological signs associated with Pb toxicity.
Male Albino rats — Pb treatment for 5 wks resulted hepatic enzymes alanine transaminase,
aspartate transaminase, and alkaline phosphatase, increased lipid
peroxidation, and decreased hepatic anti oxidant enzymes. LA or DMSA
alone, partially abrogated these effects, however, in combination
completely reversed the lipid oxidative damage.
Cr—Cromium
V—Vanadium
Pb—Lead
NAC—N acetyl cysteine
FeSO 4 —Ferrous sulphate
AlCl3—Aluminum chloride
VCl3—Vanadium chloride
CdCl2,—Cadmium chloride
CuSO 4 —Copper sulphate
CrCl3—Cromium chloride
MnCl2—Manganese chloride
NiSO 4 —Nickel sulphate
CoCl2—Cobalt chloride
LAN—" Linolenic acid
DPPD—DPPD,N-N Diphenyl –p-phynylene-diamine
LA—Lipoic acid
DMSA—Monoisoamyl DMSA
Pande and Flora
(2002)
Flora et al. (2003)
Shalan et al. (2005)
Sivaprasad et al.
(2004)