Scientific Publications by FDA Staff
Neurotoxicology 2014 May;42:49-57
Protective Effect of Acetyl-L-Carnitine on Propofol-Induced Toxicity in Embryonic Neural Stem Cells.
Liu F, Rainosek SW, Sadovova N, Fogle CM, Patterson TA, Hanig JP, Paule MG, Slikker Jr W, Wang C
Propofol is a widely used general anesthetic. A growing body of data suggests that perinatal exposure to general anesthetics can result in long-term deleterious effects on brain function. In the developing brain there is evidence that general anesthetics can cause cell death, synaptic remodeling, and altered brain cell morphology. Acetyl-L-carnitine (L-Ca), an anti-oxidant dietary supplement, has been reported to prevent neuronal damage from a variety of causes. To evaluate the ability of L-Ca to protect against propofol-induced neuronal toxicity, neural stem cells were isolated from gestational day 14 rat fetuses and on the eighth day in culture were exposed for 24 hr to propofol at 10, 50, 100, 300 and 600muM, with or without L-Ca (10muM). Markers of cellular proliferation, mitochondrial health, cell death/damage and oxidative damage were monitored to determine: 1) the effects of propofol on neural stem cell proliferation; 2) the nature of propofol-induced neurotoxicity; 3) the degree of protection afforded by L-Ca; and 4) to provide information regarding possible mechanisms underlying protection. After propofol exposure at a clinically-relevant concentration (50muM), the number of dividing cells was significantly decreased, oxidative DNA damage was increased and a significant dose-dependent reduction in mitochondrial function/health was observed. No significant effect on lactase dehydrogenase (LDH) release was observed at propofol concentrations up to 100muM. The oxidative damage at 50muM propofol was blocked by L-Ca. Thus, clinically-relevant concentrations of propofol induce dose-dependent adverse effects on rat embryonic neural stem cells by slowing or stopping cell division/proliferation and causing cellular damage. Elevated levels of 8-oxoguanine suggest enhanced oxidative damage [reactive oxygen species (ROS) generation] and L-Ca effectively blocks at least some of the toxicity of propofol, presumably by scavenging oxidative species and/or reducing their production.
|Category: Journal Article|
|PubMed ID: #24704589||DOI: 10.1016/j.neuro.2014.03.011|
|Includes FDA Authors from Scientific Area(s): Toxicological Research Drugs|
|Entry Created: 2014-04-08||Entry Last Modified: 2014-07-19|