tris(acetylacetonate)-aluminum(iii) and Myocardial-Infarction

Aluminum lactate [Al(lact)3] (hydrophilic, hydrolytically unstable) and aluminum acetylacetonate [Al(acae)3] (lipophilic, hydrolytically stable) were tested as potential toxicants to rabbits upon IV administration both as aqueous solutions and as liposome suspensions. Both chemicals behaved as cardiotoxic agents when administered as aqueous solutions, but Al(acae)3 was at least two orders of magnitude more active than Al(lact)3. Al(acae)3, but not Al(lact)3, caused myocardial infarcts resembling those in humans (with contraction bands) at doses as low as 0.24 mg/kg body weight, as well as a prominent acanthocytosis. Al(lact)3, when administered as a liposome suspension, was about 300 times more toxic than in aqueous solution, although cardiac damage was not infarctual in character. Both chemical and physical speciation of aluminum(III) thus play an essential role in determining the toxicity of the metal.

Topics: Aluminum; Animals; Heart; Lactates; Lactic Acid; Liposomes; Myocardial Infarction; Myocardium; Organometallic Compounds; Pentanones; Rabbits; Solutions

Aluminum acetylacetonate was administered to New Zealand white rabbits as liposome preparations and was found to distribute approximately 1:1 between water and phosphatidylcholine dipalmitoyl vesicles. Biochemical monitoring proved that after 2 weeks of daily injection of 40 micrograms of Al(III) in the above form, the animals developed significant signs of cardiac suffering, evidenced by variations in lactic dehydrogenase and creatinine phospokinase. Histopathologic investigation revealed that aluminum acetylacetonate caused unambiguous myocardial infarcts, characterized by myocardial contraction bands. In contrast, injection of Al(III) as a simple salt (lactate, 20 mg/day for 3 weeks) gave a less severe myocardiopathy, certainly not infarctual. Aluminum acetylacetonate given to rabbits appears to be, to our knowledge, the only chemical tool able to mimic spontaneous infarction situations in humans.

Topics: Animals; Creatine Kinase; Drug Carriers; Ketones; L-Lactate Dehydrogenase; Liposomes; Myocardial Infarction; Organometallic Compounds; Pentanones; Rabbits