Retinol but not retinoic acid can enhance the glutathione level, in a manner similar to β-carotene, in a murine cultured macrophage cell line.

Scope: We evaluated the potential of retinol and retinoic acid (RA) to enhance intracellular glutathione (GSH) levels in a murine cultured macrophage cell line, RAW264, to investigate whether the RA signaling pathway is involved in the β-carotene-induced GSH enhancement.

Methods And Results: We examined GSH levels in RAW264 cells cultured in media supplemented with β-carotene and various inhibitors (ER50891 for RA receptor (RAR)α, CD2665 for RARβ/γ, or HX531 for all subtypes of retinoid X receptor (RXR)), to verify each inhibitor's activity against β-carotene, as well as in media supplemented with various stimulants (AM80 for RARα, CD2314 for RARβ, CD437 for RARγ, or SR11237 for RXR), to compare their activity with that of β-carotene. We also examined the GSH level and glutamate-cysteine-ligase (GCL) expression in RAW264 cells cultured in all- RA- or retinol-supplemented media. Enhanced GSH production was not inhibited by any tested antagonist, and, apart from β-carotene, no agonist induced GSH production. Retinol, but not all- RA, enhanced GSH synthesis and increased GCL expression, similar to that observed with β-carotene.

Conclusion: The RA signaling pathway may not be involved in the β-carotene-induced enhancement of GSH levels in RAW264 cells, whereas, like β-carotene, retinol can enhance the GSH level and GCL expression.