Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Valerio Leoni x
Clear All Modify Search
Giuseppe Poli Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Turin, Italy

Search for other papers by Giuseppe Poli in
Google Scholar
PubMed
Close
,
Noemi Iaia Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Turin, Italy

Search for other papers by Noemi Iaia in
Google Scholar
PubMed
Close
,
Valerio Leoni Laboratory of Clinical Chemistry, Hospital of Desio, ASST Brianza, School of Medicine and Surgery, University of Milano Bicocca, Milan, Italy

Search for other papers by Valerio Leoni in
Google Scholar
PubMed
Close
, and
Fiorella Biasi Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Turin, Italy

Search for other papers by Fiorella Biasi in
Google Scholar
PubMed
Close

In a Western or Westernized diet, the abundant cholesterol is invariably associated with the presence of biochemically reactive oxysterols, the amount of which mainly depends upon the autoxidation degree of cholesterol itself, during food harvesting, production and storage. Oxysterols, in the average amount and composition detected in a high-cholesterol diet, display remarkable pro-inflammatory and cytotoxic effects on the gut epithelium. Moreover, in a low micromolar range, they may change the physiological level and membrane localization of tight junctions of the intestinal epithelial barrier, which then become leaky and permeable to microbiota. This combination of toxic effects possibly exerted by dietary oxysterols likely contributes to the impairment of the microbiota–gut–brain axis, through both direct and indirect mechanisms hereby reviewed. Importantly, dietary oxysterols are absorbed like cholesterol and circulate in the bloodstream, mainly within LDLs, rendering these micelles more oxidized and dangerous. Last but not the least, dietary oxysterols may deeply interfere with correct gut–brain signalling because of the redox pathways they are hyper-regulating and sustaining. In conclusion, protective dietary measures should be adopted, including restricted consumption of cholesterol-rich food and reduction of cholesterol autoxidation in food production and storage, for instance by supplementation of food with flavonoids and/or other bioactive substances with strong anti-oxysterol properties.

Open access
Valerio Leoni Laboratory of Clinical Chemistry, Hospital of Desio, ASST-Brianza and Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

Search for other papers by Valerio Leoni in
Google Scholar
PubMed
Close
,
Claudio Caccia Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy

Search for other papers by Claudio Caccia in
Google Scholar
PubMed
Close
,
Federica Vitarelli Laboratory of Clinical Chemistry, Hospital of Desio, ASST-Brianza and Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

Search for other papers by Federica Vitarelli in
Google Scholar
PubMed
Close
,
Andrea Civra Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano (Turin), Italy

Search for other papers by Andrea Civra in
Google Scholar
PubMed
Close
,
David Lembo Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano (Turin), Italy

Search for other papers by David Lembo in
Google Scholar
PubMed
Close
,
Roberta Cavalli Department of Drug Science and Technology, University of Turin, Italy

Search for other papers by Roberta Cavalli in
Google Scholar
PubMed
Close
,
Marco Adami Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy

Search for other papers by Marco Adami in
Google Scholar
PubMed
Close
,
Davide Risso Soremartec Italia Srl, Ferrero Group, Alba, CN, Italy

Search for other papers by Davide Risso in
Google Scholar
PubMed
Close
,
Roberto Menta Soremartec Italia Srl, Ferrero Group, Alba, CN, Italy

Search for other papers by Roberto Menta in
Google Scholar
PubMed
Close
, and
Giuseppe Poli Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano (Turin), Italy

Search for other papers by Giuseppe Poli in
Google Scholar
PubMed
Close

Background

The side chain 27-hydroxycholesterol has been reported to inhibit the replication of several pathogen viruses, including herpes simplex virus, rhinovirus, rotavirus and SARS-CoV-2, in in vitro and ex vivo models.

Objective

In view of a future potential therapeutic use of 27-hydroxycholesterol, a pilot pharmacokinetic study was set up.

Methods

This active substance was complexed with 2-hydroxypropyl-β-cyclodextrin and orally administered in a single dose to CD1 male mice; its recovery in plasma and a few tissues up to 24 h post-treatment was evaluated.

Results

The absorption of the oxysterol by the small intestine was moderate, due to its physicochemical properties, but still relevant and rapid, showing a peak at 1 h after supplementation and being almost completed 24 h after treatment. 27-Hydroxycholesterol appeared to be a high hepatic extraction drug, possibly with an extrahepatic component contributing to the total clearance.

Conclusions

Following the oral 25 mg/kg dosing, plasma levels of 27-hydroxycholesterol showed an average steady-state concentration similar to that shown to be able to inhibit the replication of all viruses tested so far in in vitro models.

Significance statement

The first pharmacokinetic data relative to a natural oxysterol administered p.o. are reported. Data should contribute to further elucidate oxysterol pathophysiology and guide non-clinical studies aiming at investigating possible therapeutic use of 27-hydroxycholesterol or its analogs.

Open access