Plasma cardiac necrosis markers C-troponin I and creatine kinase, associated with increased malondialdehyde levels, induced in rabbits by means of 5-aminolevulinic acid injection.
A number of papers have described high levels of 5-aminolevulinic acid in cases of heart damage due to acute myocardial infarction, acute intermittent porphyria or chronic kidney failure, but it is not known whether the heart damage is directly associated with 5-aminolevulinic acid. The aim of this study was to verify whether such an association exists by injecting rabbits with 5-aminolevulinic acid and searching for the appearance of cardiac necrosis markers and histological heart alterations, and investigate whether the cardiotoxic activity of 5-aminolevulinic acid may involve peroxidation by seeking the presence of the peroxide marker malondialdehyde. The administration of 5-aminolevulinic acid led to the appearance of c-troponin I and creatine kinase, induced histological heart alterations and increased the malondialdehyde levels. The plasma levels of malondialdehyde and cardiac necrosis markers were also measured after the injection of 5-aminolevulinic acid in combination with the daunorubicin agent inducing peroxidation. The combined administration very significantly increased the plasma levels of 5-aminolevulinic acid, malondialdehyde, and the cardiac necrosis markers c-troponin I and creatine kinase. It therefore seems that there is a close relationship between altered 5-aminolevulinic acid levels, malondialdehyde and cardiac necrosis markers, which is attributable to the capacity of 5-aminolevulinic acid to generate toxic oxygen species that damage the heart. High plasma 5-aminolevulinic acid levels should be considered a factor contributing to cardiotoxicity and to the appearance of cardiac necrosis markers.
Dipartimento di Farmacologia, Università di Milano, IT-20129 Milano, Italia. arnaldo.pinelli@unimi.it
Arnaldo
A
Pinelli
Silvio
S
Trivulzio
Sergio
S
Brenna
Giuseppe
G
Rossoni
D000622:Aminolevulinic Acid / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003402:Creatine Kinase / Q000097:blood*; D003630:Daunorubicin / Q000494:pharmacology; D007267:Injections; D008297:Male; D008315:Malondialdehyde / Q000097:blood*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D011817:Rabbits; D019210:Troponin I / Q000097:blood*
D015415:Biomarkers; D019210:Troponin I; D008315:Malondialdehyde; D000622:Aminolevulinic Acid; D003402:Creatine Kinase; D003630:Daunorubicin