Intestine permeability of S-nitrosoglutathione as a potential nitric oxide donor via oral administration
Abstract
Nitric oxide (NO) is a gaseous messenger which plays an important role in the vascular system homeostasis. Its origin includes both endogenous (catabolism of arginine catalyzed by endothelial NO synthase) and exogenous (intake of drinking water and foods) sources. The endogenous NO production decreases within ageing and cardiovascular diseases (CVDs) related to endothelial dysfunction, thus exogenous source of NO has to supply. Drugs actually used as NO donors have major drawbacks such as oxidative stress induction and tolerance phenomenon. Numerous studies highlight the potency of low molecular weight S-nitrosothiols as NO donors because they do not exhibit the previously cited side effects. However, very few reports have been focused on their bioavailability after oral administration which represents the most convenient route for the chronic treatment of CVDs.
We presently study the intestine permeability of S-nitrosoglutathione (GSNO) as a NO donor by using an ex vivo model: monolayer of differentiated Caco-2 cells. NO species (nitrite, nitrate and S-nitrosothiols) apparent permeabilities were measured with the help of a fluorogenic probe (i.e. 2,3-diaminonaphthalene) and compared with reference drugs commonly used to evaluate intestine permeability. Some perspectives to improve the oral bioavailability of GSNO are indicated.