In vivo assessment of intracellular redox state in rat liver using hyperpolarized [1-¹³ C]Alanine.

ABSTRACT:

Purpose

The intracellular lactate to pyruvate concentration ratio is a commonly used tissue assay biomarker of redox, being proportional to free cytosolic [NADH]/[NAD⁺ ]. In this study, we assessed the use of hyperpolarized [1-¹³ C]alanine and the subsequent detection of the intracellular products of [1-¹³ C]pyruvate and [1-¹³ C]lactate as a useful substrate for assessing redox levels in the liver in vivo.

Methods

Animal experiments were conducted to measure in vivo metabolism at baseline and after ethanol infusion. A solution of 80-mM hyperpolarized [1-¹³ C]alanine was injected intravenously at baseline (n = 8) and 45 min after ethanol infusion (n = 4), immediately followed by the dynamic acquisition of ¹³ C MRS spectra.

Results

In vivo rat liver spectra showed peaks from [1-¹³ C] alanine and the products of [1-¹³ C]lactate, [1-¹³ C]pyruvate, and ¹³ C-bicarbonate. A significantly increased ¹³ C-lactate/¹³ C-pyruvate ratio was observed after ethanol infusion (8.46 ± 0.58 at baseline versus 13.58 ± 0.69 after ethanol infusion; P < 0.001) consistent with the increased NADH produced by liver metabolism of ethanol to acetaldehyde and then acetate. A decrease in ¹³ C-bicarbonate production was also noted, potentially reflecting ethanol-induced mitochondrial redox changes.

Conclusion

A method to measure in vivo tissue redox using hyperpolarized [1-¹³ C]alanine is presented, with the validity of the proposed ¹³ C-pyruvate/¹³ C-lactate metric tested using an ethanol challenge to alter liver redox state. Magn Reson Med 77:1741-1748, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

SUBMITTER: Park JM 

PROVIDER: S-EPMC5523144 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature