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Modulation of gastrointestinal permeability of low-molecular-weight heparin by L-arginine: in-vivo and in-vitro evaluation.
J Pharm Pharmacol 2006; 58(5):591-8JP

Abstract

L-Arginine is the principal physiological precursor of nitric oxide (NO, a key neurotransmitter) that plays a versatile role in the physiology of the gastrointestinal tract. In this study, the efficacy of L-arginine in enhancing intestinal absorption of ardeparin, a low-molecular-weight heparin (LMWH) was investigated in Caco-2 cell monolayers and a rat model. Regional permeability studies using rat intestine were performed using a modified Ussing chamber. Cell viability in the presence of various concentrations of enhancer was determined by MTT assay. Furthermore, the eventual mucosal epithelial damage was histologically evaluated. LMWH formulated with L-arginine was administered orally to male Sprague-Dawley rats and the absorption of LMWH was determined by measuring plasma anti-factor Xa activity. Higher ardeparin in-vitro permeability (approximately 3 fold) compared with control was observed in the presence of 2% L-arginine. Regional permeability studies indicated predominant absorption in the colon region. Cell viability studies showed no significant cytotoxicity below 0.8% L-arginine. The oral bioavailability of ardeparin formulated with L-arginine (250 mg kg(-1)) was increased by approximately 2 fold compared with control. The formulation was well tolerated by the rats and no abnormal histopathological findings were observed in intestinal tissues of rats exposed to L-arginine. These results suggest that L-arginine may be useful in enhancing the intestinal absorption of LMWHs.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16640827

Citation

Motlekar, Nusrat Abbas, et al. "Modulation of Gastrointestinal Permeability of Low-molecular-weight Heparin By L-arginine: In-vivo and In-vitro Evaluation." The Journal of Pharmacy and Pharmacology, vol. 58, no. 5, 2006, pp. 591-8.
Motlekar NA, Srivenugopal KS, Wachtel MS, et al. Modulation of gastrointestinal permeability of low-molecular-weight heparin by L-arginine: in-vivo and in-vitro evaluation. J Pharm Pharmacol. 2006;58(5):591-8.
Motlekar, N. A., Srivenugopal, K. S., Wachtel, M. S., & Youan, B. B. (2006). Modulation of gastrointestinal permeability of low-molecular-weight heparin by L-arginine: in-vivo and in-vitro evaluation. The Journal of Pharmacy and Pharmacology, 58(5), pp. 591-8.
Motlekar NA, et al. Modulation of Gastrointestinal Permeability of Low-molecular-weight Heparin By L-arginine: In-vivo and In-vitro Evaluation. J Pharm Pharmacol. 2006;58(5):591-8. PubMed PMID: 16640827.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of gastrointestinal permeability of low-molecular-weight heparin by L-arginine: in-vivo and in-vitro evaluation. AU - Motlekar,Nusrat Abbas, AU - Srivenugopal,Kalkunte Srirangachar, AU - Wachtel,Mitchell S, AU - Youan,Bi-Botti Celestin, PY - 2006/4/28/pubmed PY - 2006/9/30/medline PY - 2006/4/28/entrez SP - 591 EP - 8 JF - The Journal of pharmacy and pharmacology JO - J. Pharm. Pharmacol. VL - 58 IS - 5 N2 - L-Arginine is the principal physiological precursor of nitric oxide (NO, a key neurotransmitter) that plays a versatile role in the physiology of the gastrointestinal tract. In this study, the efficacy of L-arginine in enhancing intestinal absorption of ardeparin, a low-molecular-weight heparin (LMWH) was investigated in Caco-2 cell monolayers and a rat model. Regional permeability studies using rat intestine were performed using a modified Ussing chamber. Cell viability in the presence of various concentrations of enhancer was determined by MTT assay. Furthermore, the eventual mucosal epithelial damage was histologically evaluated. LMWH formulated with L-arginine was administered orally to male Sprague-Dawley rats and the absorption of LMWH was determined by measuring plasma anti-factor Xa activity. Higher ardeparin in-vitro permeability (approximately 3 fold) compared with control was observed in the presence of 2% L-arginine. Regional permeability studies indicated predominant absorption in the colon region. Cell viability studies showed no significant cytotoxicity below 0.8% L-arginine. The oral bioavailability of ardeparin formulated with L-arginine (250 mg kg(-1)) was increased by approximately 2 fold compared with control. The formulation was well tolerated by the rats and no abnormal histopathological findings were observed in intestinal tissues of rats exposed to L-arginine. These results suggest that L-arginine may be useful in enhancing the intestinal absorption of LMWHs. SN - 0022-3573 UR - https://www.unboundmedicine.com/medline/citation/16640827/Modulation_of_gastrointestinal_permeability_of_low-molecular-weight_heparin_by_L-arginine:_in-vivo_and_in-vitro_evaluation L2 - https://doi.org/10.1211/jpp.58.5.0003 DB - PRIME DP - Unbound Medicine ER -