Oxidative Stress as a Common Key Event in Developmental Neurotoxicity

Table 1

Developmental neurotoxins targeting antioxidant enzymes.

Chemical	Exposure, species	Toxicities on antioxidant enzymes in the developing brain	Other findings in pups	References
Pb	Pregnant rats were allowed access to 0.1% PbAc in drinking water ad libitum from GD1 to PND21. Blood and brain Pb concentrations in the pups at PND28 were 5 μg/dL and 7 μg/g dry mass, respectively	Both SOD2 and GPx activities were decreased in FC, HC, and CB on PND28. Both SOD1 and CAT activities were decreased in HC on PND28	The concentrations of Se, Zn, Cu, and Mn were decreased in FC, HC, and CB on PND28	[25]
Pb	Pregnant rats were given access to drinking water containing 0.2% PbAc from GD5 to PND21. Brain Pb concentrations at PND21 were ~20 μg/g	Both SOD and GPx activities were decreased in CB shortly after exposure	Locomotor activities were impaired on PD31-33. Purkinje cell densities were decreased in PD33. Coadministration of melatonin alleviated the DNT of Pb	[26]
Pb	Pregnant rats were given access to drinking water containing 0.2% PbAc from GD6 to PND21	The activities of SOD1, CAT, GPX, and XO were decreased in both HC and CB on PND21, 28, 35, and 60	Calcium supplementation ameliorated the DNT of Pb	[27]
Pb	Male rats, aged 4-5 weeks, were injected IP with PbAc at 10–60 mg/kg once daily for 5 days	SOD activity was decreased in both FC and HC shortly after exposure	Bax expression and neuronal apoptosis were increased in FC and HC shortly after exposure. Coadministration of t-BHQ (activator of Nrf2) suppressed the DNT of Pb	[28]
MeHg	Pregnant mice were given access to drinking water containing 5 ppm MeHg (~400 μg/kg/day) from postmating to PND21	TrxR activity was decreased in both the cerebrum and CB in male on PND21. GPx activity was decreased in the cerebrum in male on PND21	TrxR and GPx activities in the cytoplasmic extract of CB were increased in female on PND21	[36]
As	Pregnant rats were given access to drinking water containing As 100 ppm from GD6 to PND21	The activities of SOD1, SOD2, CAT, GPX, and GR were decreased in CC, HC, and CB on PND21, PND28, and 3 months old	Lipid peroxidation and the expression of caspase-3/9 mRNA were increased in CC, HC, and CB on PND21, PND28, and 3 months old	[45]
As	Pregnant rats were injected IP with 2–4 mg/kg As once daily from GD6 to PND21	CAT activity was decreased in FC, HC, and CS on PND22 and 45. SOD activity was decreased in FC, HC, and CS on PND22	Expression of Bax and caspase-3 proteins was increased in FC, HC, and CS on PND22 and 45	[46]

GD: gestational day; PND: postnatal day; TrxR: thioredoxin reductase; GPX: glutathione peroxidase; SOD: superoxide dismutase; GR: glutathione reductase; FC: frontal cortex; CC: cerebral cortex; HC: hippocampus; CB: cerebellum; CS: corpus striatum; IP: intraperitoneal.