Interaction of dexamethasone with acetylsalicylic acid in mice.
The effect of acetylsalicylic acid (ASA, 160 mg/kg b.wt.) and dexamethasone (DEX, 15 mg/kg b.wt.) on ASA antinociception and toxicity when administered orally alone or in combination for 4 consecutive days was studied in male albino mice. ASA antinociception decreased after repeated ASA administration. Bleeding time was prolonged and the intestinal ASA esterase activity was increased, which was probably related to the increased ASA general toxicity in ASA-treated animals. There were no changes in the blood alkaline content, in the ulcerogenic or hepatotoxic effect of ASA, nor in the hepatic monooxygenase activity (ethylmorphine N-demethylase and aniline hydroxylase and the cytochrome P450 and b-5 content). DEX administered alone exerted a significant antinociceptive effect, increased both acute ASA toxicity and aniline hydroxylase activity and decreased body growth. However, DEX did not change the bleeding time, the alkaline blood content nor the intestinal esterase activity. The combination of ASA and DEX did not increase the ASA antinociceptive effect nor the general and specific toxicity of ASA. DEX in combination even abolished the effect of ASA on intestinal ASA esterase and on bleeding time. DEX also increased the hepatic cytochrome P450 content and did not change the ulcerogenic effect of ASA nor the alkaline blood content.
Tantcheva
L
L
Department of Drug Toxicology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Stoytchev
T
T
Rangelova
D
D
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D001241:Aspirin / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D001760:Bleeding Time; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D004347:Drug Interactions; D004950:Esterases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D010146:Pain / Q000517:prevention & control*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D003907:Dexamethasone; D004950:Esterases; D001241:Aspirin