A cellular mechanism for imidocarb retention in edible bovine tissues

• Published in: Toxicology letters Vol. 87; no. 2; pp. 61 - 68
• Main Authors: Moore, Andrea S., Coldham, Nick G., Sauer, Maurice J.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.10.1996; Amsterdam Elsevier Science
• Subjects: ADN; ANIMAL TISSUES; Animals; ANTIPROTOZOAIRE; ANTIPROTOZOAL AGENTS; Antiprotozoal Agents - blood; Antiprotozoal Agents - metabolism; BABESIA BOVIS; Binding; BINDING PROTEINS; Binding, Competitive; Biological and medical sciences; BOVINAE; Bovine liver; Carbon Radioisotopes; Cattle; Cell Size; CELLS; CELLULE; CELULAS; DNA; DNA - metabolism; ERITROCITOS; ERYTHROCYTE; ERYTHROCYTES; FOIE; Food Contamination; Food toxicology; Hemoglobins - metabolism; Hepatocytes; HIGADO; Imidocarb; Imidocarb - blood; Imidocarb - metabolism; Isotope Labeling; LIVER; Liver - cytology; Liver - metabolism; Medical sciences; MEDICAMENTOS CONTRA PROTOZOARIOS; Nucleic acids; Orosomucoid - metabolism; PROTEINAS AGLUTINANTES; PROTEINE DE LIAISON; RNA - metabolism; Serum Albumin, Bovine - metabolism; TEJIDOS ANIMALES; TISSU ANIMAL; Toxicology; Binding; Bovine liver; Nucleic acids; Hepatocytes; Erythrocytes; Imidocarb; RNA; Toxicity; Liver; Red blood cell; Ox; Molecular interaction; Veterinary medicine; In vitro; Antiprotozoal agent; Vertebrata; Biological fixation; Mammalia; Hepatocyte; Residue; Animal; DNA; Parasiticid; Digestive diseases; Artiodactyla; Beef; Mechanism of action; Ungulata; Nucleic acid
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/0378-4274(96)03705-8

Imidocarb dipropionate, formulated as Imizol TM, is used for the treatment and prophylaxis of bovine babesiosis. Several studies have shown that imidocarb remains detectable in edible ovine and bovine tissues for several months after dosing but the mechanism of retention remains unknown. In this study, the mechanism of imidocarb retention was investigated by measuring the binding of [ 14C]imidocarb to bovine hepatocytes, erythrocytes, sub-cellular fractions and isolated bovine macromolecules. The proportion of [ 14C]imidocarb (10 μM) bound to cells in suspension culture (1 × 10 7cells·ml −1) was found to be substantially greater to hepatocytes (56.5%) than to erythrocytes (4.6%). Studies with washed erythrocytes reconstituted in plasma indicated that approximately 70% of the [ 14C]imidocarb was bound to plasma proteins, 10%) to erythrocytes, and 20%) remained free. Measurement of [ 14C]imidocarb binding to sub-cellular fractions prepared from bovine liver revealed preferential accumulation in the nuclear, rather than in the mitochondrial, microsomal or cytosolic fractions. Binding capacities of selected bovine macromolecules for [ 14C]imidocarb were in the order deoxy-ribonucleic acid (DNA)  ribonucleic acid (RNA) > α 1-acid glycoprotein (AGP) > serum albumin (BSA) > haemoglobin (Hb). DNA binding sites for imidocarb remained unsaturated over the concentration range 0–100 μM [ 14C]imidocarb. Competitive binding studies between imidocarb and pentamidine or spermidine provided evidence for common DNA binding sites. These studies indicated that preferential binding of [ 14C]imidocarb to hepatocytes compared with erythrocytes observed in vitro was a result of substantial reversible binding to nucleic acids and that the same cellular mechanism may be implicated in the slow elimination of imidocarb from edible tissues in vivo.