| Evaluation of mucosal damage of surfactants in rat jejunum and colon. | |
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MedLine Citation:
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PMID: 7766919 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Surfactants are one of the most frequently used adjuvants in oral pharmaceutical preparations, used primarily as solubilizers, stabilizers, emulsifiers, and wetting agents. However, surfactants can disrupt normal membrane structure. In this study, lactate dehydrogenase (LDH) and mucus were evaluated as potential markers of intestinal damage in a single-pass in situ perfusion model in the rat. The release of LDH and mucus into the intestinal lumen of the rat following perfusion of the nonionic surfactants Tween 80 and Triton X-100 was determined. The release rate of LDH increased in the order saline < Tween 80 < Triton X-100 in both jejunum and colon. LDH release rate was approximately three times lower in the colon than in the jejunum, but relative effects of nonionic surfactants were comparable between regions. In addition, the rate of LDH release in the jejunum increased with decreasing perfusion rates for both saline and Tween groups and with increasing Tween 80 concentrations. At each flow rate studied, mucus release rate was greater in the presence of Tween 80 and Triton X-100 than saline, but there was no significant difference between the effect of Tween 80 and Triton X-100 on mucus release rate. When perfusion of Triton X-100 was followed by saline, rates of both mucus and LDH release returned to baseline values, suggesting damage is reversible. Histological damage agreed with trends observed in LDH and mucus release rates. This model allows for early evaluation of intestinal damage due to both excipients and active ingredients and simultaneous measurement of drug absorption. |
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Authors:
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R L Oberle; T J Moore; D A Krummel |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of pharmacological and toxicological methods Volume: 33 ISSN: 1056-8719 ISO Abbreviation: J Pharmacol Toxicol Methods Publication Date: 1995 Apr |
Date Detail:
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Created Date: 1995-07-05 Completed Date: 1995-07-05 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9206091 Medline TA: J Pharmacol Toxicol Methods Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 75-81 Citation Subset: IM |
Affiliation:
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Ciba-Geigy Corporation, Ardsley, New York 10502, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Colon / drug effects, pathology Intestinal Mucosa / drug effects*, enzymology, pathology Jejunum / drug effects, pathology L-Lactate Dehydrogenase / metabolism Male Microscopy, Electron, Scanning Mucus / drug effects Octoxynol / toxicity* Polysorbates / toxicity* Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Polysorbates; 9002-93-1/Octoxynol; EC 1.1.1.27/L-Lactate Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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