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

Abstract

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.

Acute treatment with the organochalcogen 3‐butyl‐1‐phenyl‐2‐(phenyltelluro)oct‐en‐1‐one produces behavioral changes and inhibition of creatine kinase activity in the brain of rats

“…Our present result of CK inhibition caused by the organotellurium obtained in an acute model corroborates with a recent work from our group showing that the same compound is able to reduce CK activity in mitochondrial and cytosolic fractions from cerebral cortex and cerebellum of 30‐day‐old rats in an in vitro model (Andrade et al, 2010). Therefore, it may be presumed that this compound can cross the blood–brain barrier, which is in accordance with its high lipophilicity and the effects elicited by other organotellurium compounds in the CNS (Nogueira et al, 2001, 2004) and that inhibition of CK by 3‐butyl‐1‐phenyl‐2‐(phenyltelluro)oct‐en‐1‐one could be involved in the toxicity caused by the orcanochalcogens.…”

“…Considering that organochalcogens can react with reduced cysteinyl residues from proteins, which may cause, in the case of the enzymes, the loss of their catalytic activity (Nogueira et al, 2004) and that our group recently demonstrated that an in vitro treatment with 3‐butyl‐1‐phenyl‐2‐(phenyltelluro)oct‐en‐1‐one was capable to reduce the activity of CK, a crucial enzyme for energy homeostasis (Andrade et al, 2010), in the present work we investigated the effects of the acute treatment with this organotellurium on the activity of brain CK and on behaviors in the open field test of 30‐day‐old rats.…”

Sub-acute administration of (S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate induces toxicity and oxidative stress in mice: unexpected effects of N-acetylcysteine

“…The mechanisms of toxicity by organotellurium compounds may be related to the oxidation of thiol groups of important biomolecules (Nogueira et al 2004), the replacement of selenium in selenoproteins (such as thioredoxin reductase) (Engman et al 2000), and the capacity of Te compounds to induce the formation of reactive oxygen species (ROS) (Chen et al 2001; Funchal et al 2011; de Andrade et al 2010). On the other hand, pharmacological and/or antioxidants properties of tellurium compounds have also been reported in the literature (Ávila et al 2011; Avila et al 2012), including antitumor and chemoprotective effects (Engman et al 2000; Cunha et al 2005), and glutathione peroxidase (GPx) like activity (Engman et al 1994).…”