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

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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 [1-13C]alanine and the subsequent detection of the intracellular products of [1-13C]pyruvate and [1-13C]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 [1-13C]alanine was injected intravenously at baseline (n = 8) and 45 min after ethanol infusion (n = 4), immediately followed by the dynamic acquisition of 13C MRS spectra.

Results

In vivo rat liver spectra showed peaks from [1-13C] alanine and the products of [1-13C]lactate, [1-13C]pyruvate, and 13C-bicarbonate. A significantly increased 13C-lactate/13C-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 13C-bicarbonate production was also noted, potentially reflecting ethanol-induced mitochondrial redox changes.

Conclusion

A method to measure in vivo tissue redox using hyperpolarized [1-13C]alanine is presented, with the validity of the proposed 13C-pyruvate/13C-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.

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