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https://hdl.handle.net/10316/8312
Title: | Mitochondria a key role in microcystin-LR kidney intoxication | Authors: | La-Salete, R. Oliveira, M. M. Palmeira, C. A. Almeida, J. Peixoto, F. P. |
Issue Date: | 2008 | Citation: | Journal of Applied Toxicology. 28:1 (2008) 55-62 | Abstract: | Microcystins (MCs) are a group of closely related cyclic heptapeptides produced by a variety of common cyanobacteria. These toxins have been implicated in both human and livestock mortality. Microcystin-LR could affect renal physiology by altering vascular, glomerular and urinary parameters, indicating that MC-LR could act directly on the kidney. The aim of the current work was to examine the effect of MC-LR on mitochondrial oxidative phosphorylation of rat kidney isolated mitochondria.Furthermore, microcystin-LR decreased both state 3 and carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled respiration. The transmembrane potential was strongly depressed by MC-LR in a concentration dependent manner, pointing to an uncoupling effect; however, microcystin-LR did not increase the permeability of the inner mitochondria membrane to protons. Therefore, the transmembrane decrease was a consequence of a strong inhibitory effect on redox complexes. The addition of uncoupling concentrations of MC-LR to Ca2+-loaded mitochondria treated with ruthenium red resulted in mitochondrial permeability transition pore (MPTP) opening, as evidenced by mitochondrial swelling in isosmotic sucrose medium. Mitochondrial swelling in the presence of Ca2+ was prevented by cyclosporin A and was drastically inhibited by catalase and dithiothreitol, indicating the participation of mitochondrial generated reactive oxygen species in this process. From this study it can be concluded that the bioenergetic lesion promoted by microcystin-LR seems to be sufficient to explain renal injury. Copyright © 2007 John Wiley & Sons, Ltd. | URI: | https://hdl.handle.net/10316/8312 | DOI: | 10.1002/jat.1251 | Rights: | openAccess |
Appears in Collections: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
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