Assessment of non-protein thiols concentration and 99mTc-meso-HMPAO uptake in mouse brain at normoxic, hyperoxic and hypoxic ambient conditions.

Objective: Glutathione (GSH) is the main antioxidant in brain accounting for 94% of all non-protein thiols (SH) along with whom prevents free radical damage. GSH has also been described to be the major determinant of the intracellular trapping of [sup]99m[/sup]Tc-[italic]meso[/italic]-HMPAO. The aim of this study was to evaluate the capability of [sup]99m[/sup]Tc-[italic]meso[/italic]-HMPAO to detect oxido-reductive changes in the brain. This was accomplished by assessing the GSH and SH concentration and [sup]99m[/sup]Tc-[italic]meso[/italic]-HMPAO uptake changes at normoxic, hyperoxic and hypoxic conditions.

Methods: We studied 36 mice under normoxia (21% oxygen in air), severe hypoxia (10%) and hyperoxia (100%,1atm). After 30 min exposition to the desired condition 18 mice, six for each oxygen concentration level, were injected 1.85 MBq of [sup]99m[/sup]Tc-[italic]meso[/italic]-HMPAO and were kept at the same ambient condition for further 30 min. After sacrifice, radioactivity assessment was performed by an auto-well scintillation counter. Other 18 mice were sacrificed, six for each condition, after 1 hour exposure to the desired ambient condition. In this second group GSH and SH concentrations were assessed by a colorimetric assay and spectrophotometer. In all cases cortical tissue samples were taken and statistical analysis was performed by ANOVA.

Results: Cortical uptake of [sup]99m[/sup]Tc-[italic]meso[/italic]-HMPAO showed a significant increase following hyperoxia (p[lt]0.001) and a slight but not significant decrease in hypoxia.
There were no significant changes of GSH nor SH concentrations following exposition to the different conditions. Nevertheless, SH increase was positively correlated with [sup]99m[/sup]Tc-[italic]meso[/italic]-HMPAO uptake changes in the normoxia/hyperoxia comparison and GSH slight decrease in the normoxia/hypoxia comparison paralleled the [sup]99m[/sup]Tc-[italic]meso[/italic]-HMPAO uptake decrease at the same condition.

Conclusion: We found, as compared to normoxia, a significant [sup]99m[/sup]Tc-[italic]meso[/italic]-HMPAO uptake increase at hyperoxia and a slight decrease of the radiopharmaceutical uptake during hypoxia. Our results suggest that [sup]99m[/sup]Tc-[italic]meso[/italic]-HMPAO retention is regulated at the two ambient condition by different mechanisms. In hyperoxia it is proportional to the SH content in the intracellular space. In hypoxia depends on GSH concentration as well as on the increased pericellular reductive activity that is known to decrease the cellular uptake of HMPAO.

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Pagani M
Sasaki T
Furukawa T
Micucci F
Okazawa H
Kawai K
Yoshimoto M
Yonekura Y
Fujibayashi Y
44 (2003): s225.
info:cnr-pdr/source/autori:Pagani M, Sasaki T, Furukawa T, Micucci F, Okazawa H, Kawai K, Yoshimoto M, Yonekura Y, Fujibayashi Y/titolo:Assessment of non-protein thiols concentration and 99mTc-meso-HMPAO uptake in mouse brain at normoxic, hyperoxic and hy
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Ritratto di Marco Pagani
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