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Improvement of intestinal absorption of macromolecules by nitric oxide donor.
J Pharm Sci. 2000 Oct; 89(10):1296-304.JP

Abstract

Nitric oxide (NO) is one of the most versatile mediators in mammalian biology. In the present study, we investigated the absorption-enhancing effects of an NO donor, 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-N-methyl-1-propa namine (NOC7), on drugs that are poorly absorbed from the gastrointestinal tract. NOC7 significantly increased the jejunal absorption of fluorescein isothiocyanate dextrans (FDs) of different average molecular weights (4000-20,000). This enhancing effect decreased as the FD molecular weight increased. Another NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), also increased the absorption of FD-4 from the jejunum. The absorption enhancement effect of NOC7 significantly decreased after coadministration with an NO scavenger, 2-(4-carboxyphenyl)-4,4,5, 5-tetramethylimidazole-1-oxyl-3-oxide, sodium salt. Furthermore, the enhancement effect of NOC7 was reversed shortly after cessation of the enhancer treatment. Little damage by NOC7 to the intestinal mucosa was observed in terms of release of lactose dehydrogenase and protein from the intestinal mucosa. NOC7 also increased the absorption of FD-4 by the colon and rectum. The findings suggest that an NO donor can improve the absorption of macromolecules from all regions of the rat intestine with very little mucosal damage and that an NO donor can act as a potent absorption enhancer.

Authors+Show Affiliations

Department of Pharmaceutics, School of Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Koshien, Kyuban-cho, Nishinomiya, Hyogo, 663-8179, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10980504

Citation

Numata, N, et al. "Improvement of Intestinal Absorption of Macromolecules By Nitric Oxide Donor." Journal of Pharmaceutical Sciences, vol. 89, no. 10, 2000, pp. 1296-304.
Numata N, Takahashi K, Mizuno N, et al. Improvement of intestinal absorption of macromolecules by nitric oxide donor. J Pharm Sci. 2000;89(10):1296-304.
Numata, N., Takahashi, K., Mizuno, N., Utoguchi, N., Watanabe, Y., Matsumoto, M., & Mayumi, T. (2000). Improvement of intestinal absorption of macromolecules by nitric oxide donor. Journal of Pharmaceutical Sciences, 89(10), 1296-304.
Numata N, et al. Improvement of Intestinal Absorption of Macromolecules By Nitric Oxide Donor. J Pharm Sci. 2000;89(10):1296-304. PubMed PMID: 10980504.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improvement of intestinal absorption of macromolecules by nitric oxide donor. AU - Numata,N, AU - Takahashi,K, AU - Mizuno,N, AU - Utoguchi,N, AU - Watanabe,Y, AU - Matsumoto,M, AU - Mayumi,T, PY - 2000/9/12/pubmed PY - 2001/2/28/medline PY - 2000/9/12/entrez SP - 1296 EP - 304 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 89 IS - 10 N2 - Nitric oxide (NO) is one of the most versatile mediators in mammalian biology. In the present study, we investigated the absorption-enhancing effects of an NO donor, 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-N-methyl-1-propa namine (NOC7), on drugs that are poorly absorbed from the gastrointestinal tract. NOC7 significantly increased the jejunal absorption of fluorescein isothiocyanate dextrans (FDs) of different average molecular weights (4000-20,000). This enhancing effect decreased as the FD molecular weight increased. Another NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), also increased the absorption of FD-4 from the jejunum. The absorption enhancement effect of NOC7 significantly decreased after coadministration with an NO scavenger, 2-(4-carboxyphenyl)-4,4,5, 5-tetramethylimidazole-1-oxyl-3-oxide, sodium salt. Furthermore, the enhancement effect of NOC7 was reversed shortly after cessation of the enhancer treatment. Little damage by NOC7 to the intestinal mucosa was observed in terms of release of lactose dehydrogenase and protein from the intestinal mucosa. NOC7 also increased the absorption of FD-4 by the colon and rectum. The findings suggest that an NO donor can improve the absorption of macromolecules from all regions of the rat intestine with very little mucosal damage and that an NO donor can act as a potent absorption enhancer. SN - 0022-3549 UR - https://www.unboundmedicine.com/medline/citation/10980504/Improvement_of_intestinal_absorption_of_macromolecules_by_nitric_oxide_donor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(16)30659-1 DB - PRIME DP - Unbound Medicine ER -