Tantcheva L, Stoytchev T, Rangelova D
Department of Drug Toxicology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Methods Find Exp Clin Pharmacol. 1997 Jul-Aug;19(6):387-94.
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.
在雄性白化小鼠中,研究了连续4天单独口服或联合给予乙酰水杨酸(ASA,160毫克/千克体重)和地塞米松(DEX,15毫克/千克体重)对ASA镇痛作用和毒性的影响。重复给予ASA后,其镇痛作用减弱。出血时间延长,肠道ASA酯酶活性增加,这可能与ASA处理组动物中ASA总体毒性增加有关。血液碱性含量、ASA的致溃疡或肝毒性作用以及肝单加氧酶活性(乙基吗啡N-脱甲基酶、苯胺羟化酶以及细胞色素P450和b-5含量)均无变化。单独给予DEX具有显著的镇痛作用,增加了急性ASA毒性和苯胺羟化酶活性,并降低了体重增长。然而,DEX并未改变出血时间、血液碱性含量或肠道酯酶活性。ASA与DEX联合使用既未增强ASA的镇痛作用,也未增加其总体和特殊毒性。DEX联合使用甚至消除了ASA对肠道ASA酯酶和出血时间的影响。DEX还增加了肝细胞色素P450含量,且未改变ASA的致溃疡作用或血液碱性含量。