[The action of organic cadmium complexes of different degrees of hydrophobicity on rat liver mitochondria].
Cadmium inhibits many mitochondrial enzymes participating in respiratory and oxidative phosphorylation processes, with reactive SH-groups of some of these enzymes being localized in hydrophobic domains of mitochondrial membrane. A comparative investigation was made of the action of Cd2+ and two its hydrophobic complexes (a more hydrophobic one with 1, 3-bis(4-chlorbenzilidenamino) guanidine [Cd(CBG)], and a less hydrophobic one with anabazin [Cd(ANB)] on ion permeability of the mitochondrial membrane and on respiration of rat liver mitochondria in vitro. Cd2+ ions in concentration of more than 2.5 microM and in the presence of DNP decreased mitochondrial respiration in state 3 and activated in in state 4; however, in concentration higher than 20 microM Cd2+ the activation acquired a short-term character and the state 4 respiration was seen to decrease. The experiments on mitochondrial swelling in the medium containing 125 mM NH4NO3 revealed that the complex and CBG, like Cd2+, increased proton permeability of the internal mitochondrial membrane. 10 microM Cd(ANB) and Cd(CBG) had more effect on mitochondrial respiration than Cd2+ CBG (in DNP-stimulated respiration), and ANB had no effect on mitochondrial respiration. The toxicity of Cd(CBG) was higher than that of Cd2+ and Cd(ANB), due to a higher hydrophobicity of Cd(CBG). A higher activity of Cd(CBG) was suggested to be due to its hydrophobicity. In the experiments with 137Cs in succinate-energized mitochondria at 20 degrees C and 10(-8) valinomycine, the susceptibility of toxic effects caused by the complex was lower than that caused by Cd2+ in the presence of ruthenium red, which is a blocker of Ca2+ transport. A higher Cd(CBG) effect in experiments with 137Cs and RR is accounted for by the fact that these agents are transported into mitochondria via different pathways. On the contrary, the effect of RR in similar experiments with Cd(ANB) was stronger than that of Cd2+. It is assumed that transport of Cd(ANB) in mitochondria, opposite to that of Cd(CBG), is not carried out across hydrophobic domains of the mitochondrial membrane.
Korotkov
S M
SM
Glazunov
V V
VV
Rozengart
E V
EV
Suvorov
A A
AA
D000818:Animals; D002104:Cadmium / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002588:Cesium Radioisotopes; D004140:Dinitrophenols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology; D008933:Mitochondrial Swelling / Q000187:drug effects; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D014475:Uncoupling Agents / Q000494:pharmacology
D002588:Cesium Radioisotopes; D004140:Dinitrophenols; D009942:Organometallic Compounds; D014475:Uncoupling Agents; D002104:Cadmium
Deĭstvie organicheskikh kompleksov raznoĭ stepeni gidrofobnosti na mitokhondrii pecheni krysy.