Dynamics of absorption, metabolism, and excretion of 5-aminolevulinic acid in human intestinal Caco-2 cells

Abstract

5-Aminolevulinic acid (ALA) is a precursor for the biosynthesis of porphyrins and heme. Although the oral administration of ALA has been widely applied in clinical settings, the dynamics of its absorption, metabolism, and excretion within enterocytes remain unknown. In this study, after enterocytic differentiation, Caco-2 cells were incubated with 200 µM ALA and/or 100 µM sodium ferrous citrate (SFC) for up to 72 h. Both ALA and the combination of ALA and SFC promoted the synthesis of heme, without affecting the expression of genes involved in intestinal iron transport, such as DMT1 and FPN. The enhanced heme synthesis in Caco-2 cells was more pronounced under the effect of the combination of ALA and SFC than under the effect of ALA alone, as reflected by the induced expression of heme oxygenase 1 (HO-1), as well as a reduced protein level of the transcriptional corepressor Bach1. Chromatin immunoprecipitation analysis confirmed Bach1 chromatin occupancy at the enhancer regions of HO-1, which were significantly decreased by the addition of ALA and SFC. Finally, Transwell culture of Caco-2 cells suggested that the administered ALA to the intestinal lumen was partially transported into vasolateral space. These findings enhance our understanding of the absorption and metabolism of ALA in enterocytes, which could aid in the development of a treatment strategy for various conditions such as anemia.

5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro

“…2 C), suggesting that a longer incubation time for 5-ALA treatment is required to make host cells resistant to the infection. To confirm the antiviral effects in human cells, 5-ALA was also tested with SARS-CoV-2 infection in human colon-derived Caco-2 cells, which have been characterized for metabolism of exogenously supplied 5-ALA [ 16 ]. 5-ALA pretreatment for 72 h potently inhibited SARS-CoV-2 infection either with or without SFC ( Fig.…”

Predicting the Effective Dose of 5-Aminolevulinic Acid to Protect Humans From Renal Ischemia-Reperfusion Injury: A Study in Micro Miniature Pigs

“…ALA has only been tested in rodents to date, and these studies did not measure pharmacokinetics associated with pharmacodynamics. In vitro studies assumed that 5-ALA absorption levels are different in rodents, pigs, and humans and that human intestinal cells absorb only 8% of the administered 5-ALA [15]. This difference makes it difficult to predict clinical doses for humans on the basis of in vivo rodent findings.…”

Iron Metabolism in Cancer

“…Nuclear factor erythroid 2-like 2 (NRF2) and myeloid zinc finger-1 (MZF-1) could impact cancer cell growth by transcriptionally regulating FPN, FTH, and FTL expression in prostate and breast cancer [72]. FPN transcription is inhibited by transcription factor BACH1 (Btb and Cnc Homology 1) and activated by NRF2 [73]. Deacetylase SIRT2 can deacetylate and repress NRF2 nuclear localization, reducing FPN expression and iron export, thus maintaining cancer cellular iron levels [74].…”