Evaluation of copper toxicity in isolated human peripheral blood mononuclear cells and it's attenuation by zinc: ex vivo.
Copper and zinc act as a cofactor of over 300 mammalian proteins. Both have same electronic configuration therefore they are antagonist at higher individual concentration. The present study was designed with the aim to investigate the mechanisms pertaining to toxic effects of copper on human peripheral blood mononuclear cells (PBMCs) and to evaluate the cytoprotective effect of zinc on copper-induced cytotoxicity. The copper uptake into PBMCs was progressively increased with increasing concentration of metal in the growth medium. However, no significant effect on copper uptake was observed in the presence of zinc. Cell proliferation rate was decreased with increasing copper concentration. Interestingly, the proliferation rate of zinc treated PBMCs remained nearly the same as that of control cells. LD(50) of copper (115 microM) was increased six times (710 microM) in presence of zinc for PBMCs. At higher concentrations of copper (> 100 microM) decrease level of GSH was noticed. Increased levels of metallothionein in PBMCs were observed in response to zinc. DNA fragmentation studies also showed that copper produced DNA fragmentation at LD(50) (115 microM). Subsequently, zinc showed protection against DNA fragmentation caused by copper. Cell structure of PBMCs at LD(50) (115 microM copper) showed membrane bound cystic spaces and mitochondria having disrupted cristae and few myelin figures. In presence of zinc at LD(50) of copper (115 microM) cells showed improvement in mitochondrial structure and membrane bound cystic spaces. Taken together, the results of our study demonstrates that zinc play an important role in prevention of copper toxicity in peripheral blood mononuclear cells.
Singh
Rashim Pal
RP
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Kumar
Sandeep
S
Nada
Ritambra
R
Prasad
Rajendra
R
D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000633:toxicity*; D019610:Cytoprotection; D053938:DNA Fragmentation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008668:Metallothionein / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000648:ultrastructure; D013367:Submitochondrial Particles / Q000187:drug effects / Q000648:ultrastructure; D015032:Zinc / Q000494:pharmacology*
D003300:Copper; D008668:Metallothionein; D005978:Glutathione; D015032:Zinc