ABSTRACT
The use of sensitive animals in toxicological studies tends to be limited. Even though cell culture is an attractive alternative, it has some limitations. Therefore, we investigated the potential of the metabolomic profiling of the allantoic fluid (AF) from ex ovo chick embryos to predict the hepatotoxicity of valproate (VPA). To this end, the metabolic changes occurring during embryo development and following exposure to VPA were assessed using 1H-NMR spectroscopy. During embryonic development, our findings indicated a metabolism progressively moving from anaerobic to aerobic, mainly based on lipids as the energy source. Next, liver histopathology of VPA-exposed embryos revealed abundant microvesicles indicative of steatosis and was metabolically confirmed via the determination of lipid accumulation in AF. VPA-induced hepatotoxicity was further demonstrated by (i) lower glutamine levels, precursors of glutathione, and decreased ß-hydroxybutyrate, an endogenous antioxidant; (ii) changes in lysine levels, a precursor of carnitine, which is essential in the transport of fatty acids to the mitochondria and whose synthesis is known to be reduced by VPA; and (iii) choline accumulation that promotes the export of hepatic triglycerides. In conclusion, our results support the use of the ex ovo chick embryo model combined with the metabolomic assessment of AF to rapidly predict drug-induced hepatotoxicity.
ABSTRACT
The computed tomography dose index (CTDI) measured with a 10 cm long pencil ionization chamber placed in a 14 cm long PMMA phantom is typically used to evaluate the doses delivered during CT procedure. For the new generation of CT scanners, the efficiency of this methodology is low because it excludes the contribution of radiation scattered beyond the 100 mm range of integration along z. The AAPM TG111 Report proposes a new measurement modality using a small volume ionization chamber positioned in a phantom long enough to establish dose equilibrium at the location of the chamber. In this work, the AAPM report was implemented. The minimum scanning length needed to obtain cumulative dose equilibrium was evaluated. The equilibrium dose was determined and compared to CTDI values informed by the CT scanner, and the dose values were confirmed with TLD measurements. The difference between doses measured with TLD and with the ionization chamber (IC) was below 1% and the repeatability of the measurements' setup was 0.4%. The measurements showed that the scanning lengths needed to reach the cumulated dose equilibrium were 450 mm and 380 mm for the central and peripheral axes, respectively, which justifies the phantom length. For the studied clinical protocols, the doses measured were about 30% higher than those informed by the CT scanner. For the new generation of CT systems with wider longitudinal detector size or cone-beam technology, the current CTDI measurements may no longer be adequate, and the informed CTDI tends to undervalue the dose delivered. It is therefore important to evaluate CT radiation doses following the AAPM TG111 methodology.
