Identification and Evaluation of Chronic
Low-Level Pb Toxicity Biomarkers in Neonatal Rats
Rajvee Parikh, St. John’s
University Student
Marc E. Gillespie, Department of
Pharmaceutical Sciences, College of Pharmacy and Allied Health
Professions
Abstract: The deleterious health
effects of environmental Pb exposure have been observed and
documented in numerous populations. Children, in particular, are
very vulnerable to Pb toxicity. At the protein level, Pb
substitutes for polyvalent cations, such as Ca2+. In proteins that
bind Ca2+ for their function, this Pb substitution can interfere
with the function of the protein.
The focus of our research is the evaluation of molecular
biomarkers that can be used as a diagnostic of chronic low-level
toxicity. In order to identify valid molecular makers we have
focused on a more complex model system comprised of neonatal and
maternal Long evans rats. Animals were divided into four treatment
groups (n=4/group) with each group exposed to Pb acetate via
drinking water ad libitum. After parturition the pups continued
receiving Pb through lactating mothers. Pups were sacrificed on PND
35 and brains were dissected out for further biochemical analysis.
Blood Pb levels in each pup were confirmed by the ICP atomic
emission spectroscopy. Two treatment groups showed delayed
parturition and a decreased number of pups as compared to untreated
control. This effect was significant in higher concentrations of
Pb. The pups receiving the highest concentration of Pb showed a
decreased rate of development as compared to the control.
Previous toxicoproteomic work in our lab had identified the
neuronal SNARE (Soluble NSF Attachment protein Receptor) proteins
as molecular targets of low-level Pb intoxication. The neuronal
SNARE proteins SNAP-25, Synaptobrevin, and Syntaxin are vital
components of the vesicular neurotransmitter release machinery.
Using our animal model system the SNAREs and associated proteins
were evaluated. Protein expression patterns were characterized and
evaluated using traditional western gel analysis. Gene expression
patterns were characterized with RT-PCR and microarray
analysis.