First‐Pass Metabolism of Chlorophylls in Mice

• Published in: Molecular nutrition & food research Vol. 62; no. 17; pp. e1800562 - n/a
• Main Authors: Viera, Isabel, Chen, Kewei, Ríos, José J., Benito, Itziar, Pérez‐Gálvez, Antonio, Roca, María
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.09.2018
• Subjects: Absorption; Accumulation; Adenocarcinoma; Animals; Caco-2 Cells; Chlorophyll; Chlorophyll - analogs & derivatives; Chlorophyll - analysis; Chlorophyll - metabolism; Chlorophyll - pharmacokinetics; chlorophylls; Colon; Cyclopentanes - pharmacology; Deposition; Diet; Dietary intake; Esterification; Feces - chemistry; High-performance liquid chromatography; Humans; Liquid chromatography; Liver; Liver - drug effects; Liver - metabolism; Male; Metabolism; Metabolites; Mice; Mice, Inbred C57BL; Molecular modelling; pheophorbide; Phytol; Pigments, Biological - analysis; Pigments, Biological - chemistry; Proteins; Scavenger Receptors, Class B - antagonists & inhibitors; Scavenger Receptors, Class B - metabolism; Spirulina - chemistry; SR‐BI; Thiosemicarbazones - pharmacology; Tissue Distribution; chlorophylls; SR-BI; absorption; liver; pheophorbide
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201800562

Scope The dietary intake of chlorophylls is estimated to be ≈50 mg d–1. However, their first pass metabolism and systemic assimilation is not well characterized. Methods and results A group of 30 mice are fed a diet rich in chlorophylls, while 10 mice received a standard diet without chlorophylls (control group). Liver extracts are analyzed every 15 days by HPLC–ESI(+)/APCI(+)‐hrTOF– MS/MS to measure the accretion of specific chlorophyll metabolites. The chlorophyll profile found in the livers of mice fed a chlorophyll‐rich diet shows that the formation and/or absorption of pheophorbides, pyro‐derivatives, and phytyl‐chlorin e6 require the occurrence of a precise first‐pass metabolism. In addition, the apical absorption of pheorphorbide a‐rich micelles is significantly inhibited in Caucasian colon adenocarcinoma‐2 cells pre‐incubated with BLT1. Conclusion Pheophorbide a absorption is, at least partly, protein‐mediated through SR‐BI. This active absorption process could explain the specific accumulation of pheophorbide a in the livers of animals fed a chlorophyll‐rich diet. A complementary mechanism could be the de‐esterification of pheophytin a in the liver, yielding pheophorbide a and phytol, which can explain the origin of phytol in the liver. Hence, the results suggest two molecular mechanisms responsible for the accumulation of the health‐promoting compounds pheophorbide and phytol. Human intake of chlorophyll derivatives from the diet can be estimated at around 50 mg d–1. Using a mouse model, for the first time, dietary chlorophylls undergo specific metabolism and accumulate in the liver is shown. In addition, it is shown that using a specific inhibitor, pheophorbide a is actively absorbed by the human intestinal epithelium through the protein carrier SR‐BI.