Inhibition of creatine kinase activity by 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one in the cerebral cortex and cerebellum of young rats.
In the present study, we investigated the potential in vitro toxicity of the tellurium compound 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on creatine kinase activity in cerebral cortex and cerebellum of 30-day-old Wistar rats. First, enriched mitochondrial and cytosolic fractions from the two tissues were pre-incubated for 30 min in the presence or absence of 1, 5 or 20 microm of organotellurium and the creatine kinase activity was measured. The organochalcogen reduced creatine kinase activity in a concentration-dependent pattern in the two tissues studied. Furthermore, the enzyme activity was performed after pre-incubation for 30, 60 or 90 min in the presence of 5 microm of the organotellurium. The compound inhibited creatine kinase activity in a time-dependent way in the enriched mitochondrial fraction of both tissues, but not in the cytosolic fraction, indicating different mechanisms for the organochalcogen in the mitochondrial and in the cytosolic creatine kinase. Pre-incubation of tellurium compound with reduced glutathione suggests that creatine kinase activity inhibition might be caused by direct interaction with thiol groups or by oxidative stress. Our findings suggest that creatine kinase inhibition may be one of the mechanisms by which this organotellurium could cause toxicity to the rat brain.
de Andrade
Rodrigo Binkowski
RB
Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Porto Alegre, RS, Brazil.
Gemelli
Tanise
T
Guerra
Robson Brum
RB
Funchal
Cláudia
C
Wannmacher
Clovis Milton Duval
CM
D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003402:Creatine Kinase / Q000037:antagonists & inhibitors*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism
C540925:3-butyl-1-phenyl-2-(phenyltelluro)oct-2-en-1-one; D004785:Environmental Pollutants; D009942:Organometallic Compounds; D013438:Sulfhydryl Compounds; D003402:Creatine Kinase