Journal article
Toxicity, inflammation, and anti-human immunodeficiency virus type 1 activity following exposure to chemical moieties of C31G
Biomedicine & pharmacotherapy, v 59(8), pp 430-437
2005
PMID: 16154721
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
C31G, which has potent activity against the human immunodeficiency virus type 1 (HIV-1) and an established record of safety in animal studies and human trials, is a microbicidal agent comprised of a buffered equimolar mixture of two amphoteric, surface-active agents: an alkyl amine oxide (C14AO) and an alkyl betaine (C16B). Studies of long-term in vitro exposure to C31G and its constituents have suggested that the components of C31G may contribute differentially to its toxicity and efficacy. In the present studies, in vitro assays of cytotoxicity and anti-HIV-1 activity demonstrated that C16B was slightly less cytotoxic compared to either C31G or C14AO, whereas the anti-HIV-1 activities of C31G and its individual constituents were similar. In the murine model of cervicovaginal microbicide toxicity, in vivo exposure to C14AO resulted in severe cervical inflammation followed by a delayed disruption of the columnar epithelium. In contrast, exposure to C16B caused severe cervical epithelial disruption and a secondary, less intense inflammatory response. These results demonstrate that (i) there are both mechanistic and temporal differences in toxicity associated with the components of C31G not necessarily predicted by in vitro assessments of cytotoxicity and (ii) contributions of each component to the anti-HIV-1 activity of C31G appear to be equal. In addition, these findings indicate that direct and indirect mechanisms of in vivo toxicity can be observed as separate but interrelated events. These results provide further insight into the activity of C31G, as well as mechanisms potentially associated with microbicide toxicity.
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Details
- Title
- Toxicity, inflammation, and anti-human immunodeficiency virus type 1 activity following exposure to chemical moieties of C31G
- Creators
- Bradley J Catalone - Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USAShendra R Miller - Department of Microbiology and Immunology, Center for Sexually Transmitted Disease, Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USAMary Lee Ferguson - Department of Microbiology and Immunology, Center for Sexually Transmitted Disease, Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USADan Malamud - Department of Biochemistry, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USATina Kish-Catalone - Department of Microbiology and Immunology, Center for Sexually Transmitted Disease, Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USANina J Thakkar - Department of Microbiology and Immunology, Center for Sexually Transmitted Disease, Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USAFred C Krebs - Department of Microbiology and Immunology, Center for Sexually Transmitted Disease, Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USAMary K Howett - Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA 19104, USABrian Wigdahl - Department of Microbiology and Immunology, Center for Sexually Transmitted Disease, Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA
- Publication Details
- Biomedicine & pharmacotherapy, v 59(8), pp 430-437
- Publisher
- Elsevier SAS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000232464500002
- Scopus ID
- 2-s2.0-25644452139
- Other Identifier
- 991014877824604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medicine, Research & Experimental
- Pharmacology & Pharmacy