Tags

Type your tag names separated by a space and hit enter

Cytotoxicity of absorption enhancers in Caco-2 cell monolayers.
J Pharm Pharmacol. 1998 Oct; 50(10):1101-8.JP

Abstract

This study was performed to evaluate the utility of absorption enhancers with reference to mucosal cell cytotoxicity. Overall assessment of the damage to plasma, lysosomal and nuclear membranes by three absorption enhancers, sodium deoxycholate, sodium caprate and dipotassium glycyrrhizinate, was performed on Caco-2 cell monolayers. The cytotoxicities of sodium deoxycholate (0.02-0.1% w/v), sodium caprate (0.1-0.5% w/v) and dipotassium glycyrrhizinate (0.5-2% w/v) were evaluated by the trypan blue-exclusion test, the protein-release test, the neutral-red assay, the DNA--propidium iodide staining test and the test for recovery of transepithelial electrical resistance (TEER) up to 24 h after treatment with each enhancer. Sodium dodecyl sulphate (SDS; 0.1% w/v), a potent surfactant, was used as positive control. SDS at this level was significantly cytotoxic whereas dipotassium glycyrrhizinate was not cytotoxic in any tests. Results from the trypan blue-exclusion and protein-release tests showed that high concentrations of sodium caprate (0.5% w/v) and sodium deoxycholate (0.1% w/v) were significantly cytotoxic to the plasma membrane. The neutral-red assay, an indicator of damage to lysosomal membranes, revealed that 0.5% (w/v) sodium caprate had no effect whereas the uptake of neutral red was slightly increased by treatment with 0.1% (w/v) sodium deoxycholate, implying that the compound had cell-growth-enhancing activity. Nuclear-membrane damage, as evaluated by the DNA--propidium iodide staining test, was severe in cell monolayers treated with 0.5% (w/v) sodium caprate compared with that induced by 0.1% (w/v) sodium deoxycholate. In the TEER recovery test, TEER failed to recover 24 h after treatment with 0.5% (w/v) sodium caprate and 0.1% (w/v) SDS, but recovered after treatment with 0.1% (w/v) sodium deoxycholate. The recovery of TEER might be related to nuclear membrane damage and cell-growth-enhancing activity. These results indicate that of the three classes of enhancer, dipotassium glycyrrhizinate was not cytotoxic and that high concentrations of sodium caprate and sodium deoxycholate could damage plasma and nuclear membranes.

Authors+Show Affiliations

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9821655

Citation

Sakai, M, et al. "Cytotoxicity of Absorption Enhancers in Caco-2 Cell Monolayers." The Journal of Pharmacy and Pharmacology, vol. 50, no. 10, 1998, pp. 1101-8.
Sakai M, Imai T, Ohtake H, et al. Cytotoxicity of absorption enhancers in Caco-2 cell monolayers. J Pharm Pharmacol. 1998;50(10):1101-8.
Sakai, M., Imai, T., Ohtake, H., & Otagiri, M. (1998). Cytotoxicity of absorption enhancers in Caco-2 cell monolayers. The Journal of Pharmacy and Pharmacology, 50(10), 1101-8.
Sakai M, et al. Cytotoxicity of Absorption Enhancers in Caco-2 Cell Monolayers. J Pharm Pharmacol. 1998;50(10):1101-8. PubMed PMID: 9821655.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytotoxicity of absorption enhancers in Caco-2 cell monolayers. AU - Sakai,M, AU - Imai,T, AU - Ohtake,H, AU - Otagiri,M, PY - 1998/11/20/pubmed PY - 1998/11/20/medline PY - 1998/11/20/entrez SP - 1101 EP - 8 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 50 IS - 10 N2 - This study was performed to evaluate the utility of absorption enhancers with reference to mucosal cell cytotoxicity. Overall assessment of the damage to plasma, lysosomal and nuclear membranes by three absorption enhancers, sodium deoxycholate, sodium caprate and dipotassium glycyrrhizinate, was performed on Caco-2 cell monolayers. The cytotoxicities of sodium deoxycholate (0.02-0.1% w/v), sodium caprate (0.1-0.5% w/v) and dipotassium glycyrrhizinate (0.5-2% w/v) were evaluated by the trypan blue-exclusion test, the protein-release test, the neutral-red assay, the DNA--propidium iodide staining test and the test for recovery of transepithelial electrical resistance (TEER) up to 24 h after treatment with each enhancer. Sodium dodecyl sulphate (SDS; 0.1% w/v), a potent surfactant, was used as positive control. SDS at this level was significantly cytotoxic whereas dipotassium glycyrrhizinate was not cytotoxic in any tests. Results from the trypan blue-exclusion and protein-release tests showed that high concentrations of sodium caprate (0.5% w/v) and sodium deoxycholate (0.1% w/v) were significantly cytotoxic to the plasma membrane. The neutral-red assay, an indicator of damage to lysosomal membranes, revealed that 0.5% (w/v) sodium caprate had no effect whereas the uptake of neutral red was slightly increased by treatment with 0.1% (w/v) sodium deoxycholate, implying that the compound had cell-growth-enhancing activity. Nuclear-membrane damage, as evaluated by the DNA--propidium iodide staining test, was severe in cell monolayers treated with 0.5% (w/v) sodium caprate compared with that induced by 0.1% (w/v) sodium deoxycholate. In the TEER recovery test, TEER failed to recover 24 h after treatment with 0.5% (w/v) sodium caprate and 0.1% (w/v) SDS, but recovered after treatment with 0.1% (w/v) sodium deoxycholate. The recovery of TEER might be related to nuclear membrane damage and cell-growth-enhancing activity. These results indicate that of the three classes of enhancer, dipotassium glycyrrhizinate was not cytotoxic and that high concentrations of sodium caprate and sodium deoxycholate could damage plasma and nuclear membranes. SN - 0022-3573 UR - https://www.unboundmedicine.com/medline/citation/9821655/Cytotoxicity_of_absorption_enhancers_in_Caco_2_cell_monolayers_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3573&date=1998&volume=50&issue=10&spage=1101 DB - PRIME DP - Unbound Medicine ER -