Benzydamine protection in a mouse model of endotoxemia
| Autor: | Isabella Coletta, A. Guglielmotti, M. T. Rosignoli, Lucia Soldo, L. Aquilini, M. Pinza, Carla Landolfi |
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| Rok vydání: | 1997 |
| Předmět: |
Drug
Lipopolysaccharides Benzydamine media_common.quotation_subject Fibrosarcoma Immunology Pharmacology Mice Tumor Cells Cultured Medicine Potency Animals Mode of action Cytotoxicity Lung media_common Mice Inbred BALB C Cell Death business.industry Tumor Necrosis Factor-alpha Therapeutic effect Anti-Inflammatory Agents Non-Steroidal Endotoxemia Toxicity Tumor necrosis factor alpha Female business medicine.drug Interleukin-1 |
| Zdroj: | Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 46(9) |
| ISSN: | 1023-3830 |
| Popis: | Objective: Previous studies have shown that benzydamine (40 mg/kg s.c.) is able to inhibit tumor necrosis factor (TNF) production and to reduce mouse lethality when administered before or concomitantly with LPS. The present study was designed to further investigate benzydamine activity against LPS-induced toxicity in terms of potency and therapeutic effects.¶Methods: Female Balb/c mice were used. A dose-response curve of animal lethality versus endotoxin dose was performed (LD50 = 45 μg/mouse). Therapeutic effects were studied selecting the dose of LPS to achieve an LD100 (160 μg/mouse). Mortality was assessed daily and mice were followed for 8 days. The potential mode of action of therapeutically administered benzydamine was also investigated. TNFα and IL-1β levels were measured, at 5 h after LPS injection, both in sera and in lungs. Moreover, the drug was assayed in a TNF-dependent cytoxicity test.¶Results: Benzydamine, administered at 20 mg/kg s.c. simultaneously with the endotoxin, significantly increased LPS LD50 up to 230 μg/mouse (p < 0.05). Moreover, the drug significantly protected mice against LPS-induced lethality when administered either 30 min or 4 h after endotoxin injection (p < 0.001). Benzydamine, therapeutically administered at 20 mg/kg s.c., significantly reduced TNFα and IL-1β production induced by LPS both in serum and lungs and it was shown to inhibit TNF-dependent cytoxicity on L929 cells.¶Conclusions: These results clearly demonstrate the therapeutic activity of benzydamine in a simple model of endotoxic shock. Available data confirm the potential role of benzydamine as an anti-cytokine agent and provide suggestions for novel therapeutic applications of this anti-inflammatory drug. |
| Databáze: | OpenAIRE |
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