title: Mn bioavailability by polarized Caco-2 cells: comparison between Mn gluconate and Mn oxyprolinate.
abstract: BACKGROUND
  Micronutrient inadequate intake is responsible of pathological deficiencies and there is a need of assessing the effectiveness of metal supplementation, frequently proposed to rebalance poor diets. Manganese (Mn) is present in many enzymatic intracellular systems crucial for the regulation of cell metabolism, and is contained in commercially available metal supplements.
  
  
  METHODS
  We compared the effects of two different commercial Mn forms, gluconate (MnGluc) and oxyprolinate (MnOxP). For this purpose we used the polarized Caco-2 cells cultured on transwell filters, an established in vitro model of intestinal epithelium. Since micronutrient deficiency may accelerate mitochondrial efficiency, the mitochondrial response of these cells, in the presence of MnGluc and MnOxP, by microscopy methods and by ATP luminescence assay was used.
  
  
  RESULTS
  In the presence of both MnOxP and MnGluc a sustained mitochondrial activity was shown by mitoTraker labeling (indicative of mitochondrial respiration), but ATP intracellular content remained comparable to untreated cells only in the presence of MnOxP. In addition MnOxP transiently up-regulated the antioxidant enzyme Mn superoxide dismutase more efficiently than MnGluc. Both metal treatments preserved NADH and βNADPH diaphorase oxidative activity, avoided mitochondrial dysfunction, as assessed by the absence of a sustained phosphoERK activation, and were able to maintain cell viability.
  
  
  CONCLUSIONS
  Collectively, our data indicate that MnOxP and MnGluc, and primarily the former, produce a moderate and safe modification of Caco-2 cell metabolism, by activating positive enzymatic mechanisms, thus could contribute to long-term maintenance of cell homeostasis.
authors.affiliation: Department of Human Morphology Città Studi, Università degli Studi di Milano, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Foglieni
authors.forename: Mariangela
authors.initials: M
authors.lastname: Cavarelli
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Piscopiello
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fulgenzi
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Ferrero
mesh_terms: D001682:Biological Availability; D018938:Caco-2 Cells; D004032:Diet; D005942:Gluconates / Q000493:pharmacokinetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D008345:Manganese / Q000493:pharmacokinetics*; D018977:Micronutrients / Q000172:deficiency; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism
chemical_list: D005942:Gluconates; D018977:Micronutrients; D008345:Manganese