Abamectin affects the bioenergetics of liver mitochondria: A potential mechanism of hepatotoxicity.
Abamectin (ABA) is a macrocyclic lactone of the avermectin family used worldwide as an antiparasitic agent in farm animals and pets and as the active ingredient of insecticides and nematicides. In this study, the effects of abamectin on the bioenergetics of mitochondria isolated from rat liver were evaluated. Mitochondria are responsible for converting the energy released by electron transport and stored as the binding energy molecule ATP. Xenobiotics that interfere with its synthesis or utilization can be acutely or chronically toxic. Abamectin (5-25μM) caused concentration-dependent inhibition of the respiratory chain without affecting the membrane potential or the activity of enzymes NADH dehydrogenase or succinate dehydrogenase. This behavior is similar to oligomycin and carboxyatractyloside and suggests direct action on F(o)F(1)-ATPase and/or the adenine nucleotide translocator (ANT). ABA more pronouncedly inhibited ATPase phosphohydrolase activity in intact, uncoupled mitochondria than in freeze-thawed disrupted mitochondria. ADP-stimulated depolarization of the mitochondrial membrane potential was also inhibited by ABA. Our results indicate that ABA interacts more specifically with the ANT, resulting in functional inhibition of the translocator with consequent impairment of mitochondrial bioenergetics. This effect could be involved in the ABA toxicity to hepatocytes.
Laboratório de Bioquímica Metabólica e Toxicológica, UNESP - Univ Estadual Paulista, Campus de Dracena, 17900-000 Dracena, SP, Brazil.
Juliana C
JC
Castanha Zanoli
Marcos A
MA
Maioli
Hyllana C D
HC
Medeiros
Fábio E
FE
Mingatto
D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism
D033741:Adenine Nucleotide Translocator 1; D000871:Anthelmintics; D007306:Insecticides; D009243:NAD; C048324:abamectin; D007559:Ivermectin; D000255:Adenosine Triphosphate; D013385:Succinate Dehydrogenase; D000251:Adenosine Triphosphatases; D010100:Oxygen