This study was designed to verify the effects of fluoride (F) or Lead ( Pb) or both together on blood flu
oride and lead levels, alanine transaminase (ALT), aspartate transaminase (AST), and acetylcholine este~
rase activities as well as the morphological changes by light microscope and immunohistochemical study
of caspase3 in hippocampus of offspring rats at postnatal week 6 and 8. Sixty albino rats ( 30 males and
30 females) were used in this study. After mating, twenty-four pregnant female raJs were randomly divid
ed into 4 groups of six each. Begi11ning with day of delivery the first group served as controls and they re
ceived distilled water, the second group received sodium fluoride (NaF) in a dose of 150 mg!L, the third
group was given lead acetate 300 mg/L. Rats of the fourth group received NaF 150 mg/L + lead acetate
300 mg/L. The rats' offspring divided into 4 groups ( 10 rats in each group) at 3 weeks post natal ate and
drank by thetnselves and were given the same treatment as parental generation. Results showed that the
activities of the enzymes in all groups were significantly decreased in comparison with the control group
at both 6 and 8 weeks. Both the fluoride level in F and F + pb groups, and the lead level in the lead Cllld F
+ pb groups were significantly higher thClll the control group. At 6 weeks, morphological study of hippo
campal sub-regions of the three treated groups demonstrated degenerated neurons and the immunoposi
tive cells in the cornu ammonis-3 (CA3) zone, but at 8 weeks, they became in the CAl zone as well in Flu
oride group, in most of the pyramidal neurons and granular cell layer of dentate gyrus ( DG) in lead and
Fluoride+ lead group. In conclusion, excessive intakes ofF and lead either alone or in combination dur
ing the early developing stages of life affect the hippocampus biochemically, histopathologically and im
munohistochemically.