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.