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Characterization of the influence of nitric oxide donors on intestinal absorption of macromolecules.
Int J Pharm. 2004 Nov 22; 286(1-2):89-97.IJ

Abstract

To characterize the influence of nitric oxide (NO) donors on the intestinal absorption of macromolecules, the relationship between the release rate of NO from NO donors and their absorption-enhancing effects and the effects of several scavengers and generators on the absorption-enhancing effects of NO donor were investigated. The t1/2 values of the NO release rate from 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-1-propanamine (NOC5), 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-N-methyl-1-propanamine (NOC7) and N-ethyl-2-(1-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine (NOC12) are 25, 5 and 100min, respectively. The absorption-enhancing effects of NO donors on the absorption of fluorescein isothiocyanate dextrans with an average molecular weight of 4400 (FD-4) are NOC5 > NOC7 > NOC12 in the colon. The lowest enhancing effect of NOC12 may be due to the slow rate of NO release. The enhancing effect of NOC7 rapidly disappeared compared with the effect of NOC5. The results raise the possibility that the difference between NOC5 and NOC7 on enhancing effect is related to the t1/2 of the NO release. The NOC7-induced enhancing effect was prevented by the co-administration of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide sodium salt (C-PTIO), an NO scavenger; tiron, an O2(-) scavenger; mannitol, an OH* scavenger, and deferoxamine, peroxynitrate scavenger. Pyrogallol, an O2(-) generator, potentiated the NOC7-induced enhancing effect. These results support a role for peroxynitrate, and possibly OH*, in the NO donor-induced intestinal enhancing effect.

Authors+Show Affiliations

Department of Pharmaceutics, School of Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Koshien, Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan. koichi@mwu.mukogawa-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15501005

Citation

Takahashi, Koichi, et al. "Characterization of the Influence of Nitric Oxide Donors On Intestinal Absorption of Macromolecules." International Journal of Pharmaceutics, vol. 286, no. 1-2, 2004, pp. 89-97.
Takahashi K, Numata N, Kinoshita N, et al. Characterization of the influence of nitric oxide donors on intestinal absorption of macromolecules. Int J Pharm. 2004;286(1-2):89-97.
Takahashi, K., Numata, N., Kinoshita, N., Utoguchi, N., Mayumi, T., & Mizuno, N. (2004). Characterization of the influence of nitric oxide donors on intestinal absorption of macromolecules. International Journal of Pharmaceutics, 286(1-2), 89-97.
Takahashi K, et al. Characterization of the Influence of Nitric Oxide Donors On Intestinal Absorption of Macromolecules. Int J Pharm. 2004 Nov 22;286(1-2):89-97. PubMed PMID: 15501005.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of the influence of nitric oxide donors on intestinal absorption of macromolecules. AU - Takahashi,Koichi, AU - Numata,Nanako, AU - Kinoshita,Natsumi, AU - Utoguchi,Naoki, AU - Mayumi,Tadanori, AU - Mizuno,Nobuyasu, PY - 2004/03/06/received PY - 2004/07/01/revised PY - 2004/08/08/accepted PY - 2004/10/27/pubmed PY - 2005/5/18/medline PY - 2004/10/27/entrez SP - 89 EP - 97 JF - International journal of pharmaceutics JO - Int J Pharm VL - 286 IS - 1-2 N2 - To characterize the influence of nitric oxide (NO) donors on the intestinal absorption of macromolecules, the relationship between the release rate of NO from NO donors and their absorption-enhancing effects and the effects of several scavengers and generators on the absorption-enhancing effects of NO donor were investigated. The t1/2 values of the NO release rate from 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-1-propanamine (NOC5), 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-N-methyl-1-propanamine (NOC7) and N-ethyl-2-(1-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine (NOC12) are 25, 5 and 100min, respectively. The absorption-enhancing effects of NO donors on the absorption of fluorescein isothiocyanate dextrans with an average molecular weight of 4400 (FD-4) are NOC5 > NOC7 > NOC12 in the colon. The lowest enhancing effect of NOC12 may be due to the slow rate of NO release. The enhancing effect of NOC7 rapidly disappeared compared with the effect of NOC5. The results raise the possibility that the difference between NOC5 and NOC7 on enhancing effect is related to the t1/2 of the NO release. The NOC7-induced enhancing effect was prevented by the co-administration of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide sodium salt (C-PTIO), an NO scavenger; tiron, an O2(-) scavenger; mannitol, an OH* scavenger, and deferoxamine, peroxynitrate scavenger. Pyrogallol, an O2(-) generator, potentiated the NOC7-induced enhancing effect. These results support a role for peroxynitrate, and possibly OH*, in the NO donor-induced intestinal enhancing effect. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/15501005/Characterization_of_the_influence_of_nitric_oxide_donors_on_intestinal_absorption_of_macromolecules_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(04)00489-2 DB - PRIME DP - Unbound Medicine ER -