Table 2.
Developmental neurotoxins targeting mitochondria.
Chemical | Exposure, species | Toxicities on mitochondria in the developing brain | Other findings in pups | References |
---|---|---|---|---|
As | Pregnant rats were injected IP with 2–4 mg/kg As once daily from GD6 to PND21 | Complex II and III activities were decreased in FC, HC, and CS on PND22 and 45. Complex I and IV activities were decreased in FC, HC, and CS on PND22 | ROS and MMP were increased and decreased, respectively, in FC, HC, and CS on PND22 and 45 | [46] |
Mn | Pups were injected IP with MnCl2 (5–20 mg/kg) once daily from PND8 to PND12 | Complex I and II activities were increased and decreased, respectively, in the striatum of the pups on PND14 | ROS and caspase activity were increased in the striatum of the pups on PND14. Abnormalities in motor coordination were observed at 3-5 weeks of age | [58] |
Sevoflurane | Rats at PND7 were anesthetized with 3% sevoflurane in 40% oxygen for 4 h | The protein expression of Drp1 and Mfn2 was increased and decreased, respectively, in HC shortly after exposure | Cleaved caspase-3, cytochrome c, and apoptosis were increased in HC shortly after exposure. Abnormalities in spatial learning and memory were observed at PND30 | [65] |
General anesthesia (midazolam, isoflurane, and nitrous oxide) | Rats at PND7 were injected IP with midazolam (9 mg/kg) and then exposed for 6 h to nitrous oxide (75%), isoflurane (0.75%), and oxygen (approximately 24%) | Expression and oligomerization of Drp1 protein in mitochondria were increased in subicular and thalamic regions shortly after exposure | ROS and fission of mitochondria in the subicular region were increased shortly after exposure | [69] |
GD: gestational day; PND: postnatal day; FC: frontal cortex; HC: hippocampus; CS: corpus striatum; MMP: mitochondrial membrane potential; IP: intraperitoneal.