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Intestinal absorption of S-nitrosothiols: Permeability and transport mechanisms.

Abstract：

:S-Nitrosothiols, a class of NO donors, demonstrate potential benefits for cardiovascular diseases. Drugs for such chronic diseases require long term administration preferentially through the oral route. However, the absorption of S-nitrosothiols by the intestine, which is the first limiting barrier for their vascular bioavailability, is rarely evaluated. Using an in vitro model of intestinal barrier, based on human cells, the present work aimed at elucidating the mechanisms of intestinal transport (passive or active, paracellular or transcellular pathway) and at predicting the absorption site of three S-nitrosothiols: S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-l-cysteine (NACNO) and S-nitroso-N-acetyl-d-penicillamine (SNAP). These S-nitrosothiols include different skeletons carrying the nitroso group, which confer different physico-chemical characteristics and biological activities (antioxidant and anti-inflammatory). According to the values of apparent permeability coefficient, the three S-nitrosothiols belong to the medium class of permeability. The evaluation of the bidirectional apparent permeability demonstrated a passive diffusion of the three S-nitrosothiols. GSNO and NACNO preferentially cross the intestinal barrier though the transcellular pathway, while SNAP followed both the trans- and paracellular pathways. Finally, the permeability of NACNO was favoured at pH 6.4, which is close to the pH of the jejunal part of the intestine. Through this study, we determined the absorption mechanisms of S-nitrosothiols and postulated that they can be administrated through the oral route.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Bonetti J,Zhou Y,Parent M,Clarot I,Yu H,Fries-Raeth I,Leroy P,Lartaud I,Gaucher C

doi

10.1016/j.bcp.2018.06.018

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

21-31

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(18)30231-4

journal_volume

155

pub_type

杂志文章

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