Pyrogenic and neuroinflammatory properties of zymosan and its potential as an alternative to live yeast in antipyretic drug testing
| Autor: | Kennedy H. Erlwanger, Michael T. Madziva, Joachim Roth, Rachael Dangarembizi, Christoph Rummel, Lois M. Harden |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae lethargy Anorexia Pharmacology Cell wall 03 medical and health sciences Lethargy chemistry.chemical_compound 0302 clinical medicine medicine immune-to-brain communication lcsh:Science Circumventricular organs circumventricular organs Multidisciplinary biology Zymosan biology.organism_classification Yeast cytokines cyclooxygenase 030104 developmental biology medicine.anatomical_structure chemistry anorexia biology.protein lcsh:Q Cyclooxygenase medicine.symptom lcsh:L 030217 neurology & neurosurgery lcsh:Education |
| Zdroj: | FACETS, Vol 4, Iss 1, Pp 162-182 (2019) |
| ISSN: | 2371-1671 |
| DOI: | 10.1139/facets-2018-0045 |
| Popis: | Zymosan, an immunogenic cell wall extract of Saccharomyces cerevisiae has potential for use as an experimental pyrogen. However, the short-lived sickness responses noted with intraperitoneal and intra-articular administration of zymosan limits investigations on the long-term effectiveness of antipyretic drugs. Thus, there remains a need to establish an alternative route of zymosan administration that could induce long-lived fevers and inflammation. We injected male Sprague Dawley rats (250–300 g) subcutaneously with zymosan (30 or 300 mg/kg) or saline; n = 7–8. We measured core body temperature, cage activity, food intake and body mass for 24 h after injection. Blood and brain samples were collected at 2, 8, and 18 h after injection. Zymosan (300 mg/kg) induced fever, lethargy, and anorexia, which lasted for 24 h. Zymosan-induced sickness responses were accompanied by increased blood plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α; activation of inflammatory transcription factors (nuclear factor (NF) for IL-6, signal transducer and activator of transcription (STAT)-3, and NF-κB) in the hypothalamus and circumventricular organs; and increased hypothalamic mRNA expression of TNF-α, IL-1β, and IL-6 and rate-limiting enzymes for prostaglandin synthesis. Our results confirm the suitability of subcutaneous administration of zymosan for screening antipyretic and anti-inflammatory drugs in rats. |
| Databáze: | OpenAIRE |
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