A novel xanthine derivative counteracting in vivo tumor necrosis factor alpha toxicity in mice.

Abstract

The xanthine derivative A 802715 (1-(5-hydroxy-5-methyl)hexyl-3-methyl-7- propyl-xanthine, Hoechst AG) caused dose-dependent protection against lipopolysaccharide (LPS)-induced lethal shock in mice. In animals which had received the compound, the LPS-induced increase of serum tumor necrosis factor (TNF alpha) levels was not significantly affected. Protection against LPS-induced lethality was observed not only when A 802715 was given 1 hr before or simultaneously with LPS but also when administered 1 hr after LPS challenge. Administration of 200 mg/kg of the compound 1 hr before challenge also fully protected against lethal shock induced by intravenous administration of recombinant murine TNF alpha. It is concluded that A 802715 counteracts TNF alpha toxicity and that the drug bears the potential of therapeutic intervention in septic shock.

• Authors: M Niehörster, M Schönharting, A Wendel
• Journal: Circulatory shock (Circ Shock) Vol. 37 Issue 4 Pg. 270-3 (Aug 1992) ISSN: 0092-6213 [Print] United States
• PMID: 1446384 (Publication Type: Journal Article)

Chemical References

• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• Xanthines
• A 802715

Topics

• Animals
• Lipopolysaccharides
• Male
• Mice
• Mice, Inbred BALB C
• Shock, Septic (chemically induced, prevention & control)
• Survival Rate
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, toxicity)
• Xanthines (pharmacology)