First-Pass Metabolism of Chlorophylls in Mice

Mol Nutr Food Res. 2018 Sep;62(17):e1800562. doi: 10.1002/mnfr.201800562. Epub 2018 Aug 6.

Abstract

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.

Keywords: SR-BI; absorption; chlorophylls; liver; pheophorbide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caco-2 Cells
  • Chlorophyll / analogs & derivatives*
  • Chlorophyll / analysis
  • Chlorophyll / metabolism
  • Chlorophyll / pharmacokinetics*
  • Cyclopentanes / pharmacology
  • Diet
  • Feces / chemistry
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice, Inbred C57BL
  • Pigments, Biological / analysis
  • Pigments, Biological / chemistry
  • Scavenger Receptors, Class B / antagonists & inhibitors
  • Scavenger Receptors, Class B / metabolism
  • Spirulina / chemistry
  • Thiosemicarbazones / pharmacology
  • Tissue Distribution

Substances

  • 2-hexyl-1-cyclopentanone thiosemicarbazone
  • Cyclopentanes
  • Pigments, Biological
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Thiosemicarbazones
  • Chlorophyll
  • pheophorbide a