Experimental cadmium poisoning in sheep

Stoev, Stoycho D.; Grozeva, N.; Simeonov, R.; Борисов, Иван Михайлович; Hubenov, H.; Nikolov, Y.; Tsaneva, Magda; Lazarova, Stela

doi:10.1078/0940-2993-00333

Cited by 26 publications

(18 citation statements)

References 32 publications

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“…Expression of the endothelium-specific occluding junction protein, claudin-5, was irregular and diminished in the glomeruli and small blood vessels of the kidneys from Cdtreated rats (Jacquillet et al, 2006). Lastly, sub-chronic Cd exposure in the drinking water of sheep resulted in the proliferation of vascular endothelial cells, especially within the glomeruli (Stoev et al, 2003). Taken together, these studies would suggest a greater role of the endothelium in mediating the nephrotoxic effects of Cd than previously thought.…”

Section: Role Of the Endothelium In CD Nephrotoxicitymentioning

confidence: 87%

The vascular endothelium as a target of cadmium toxicity

2006

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Section: Role Of the Endothelium In CD Nephrotoxicitymentioning

confidence: 87%

The vascular endothelium as a target of cadmium toxicity

2006

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“…In a prior study, we reported that increasing HO-1 in cultured astrocytes by gene transfer markedly reduced their subsequent vulnerability to hemin (Teng et al, 2004). However, rapid gene transfer in the CNS may not be feasible after hemorrhage, and metallic HO-1 inducers such as cobalt and cadmium penetrate the bloodbrain barrier poorly and produce toxic effects at relatively low doses (De Boeck et al, 2003;Stoev et al, 2003). MG-132 is a low molecular weight, lipid-soluble inhibitor of the 26S proteasome that inhibits Nrf2 degradation in cultured hepatoma cells (Stewart et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Increasing Expression of Heme Oxygenase-1 by Proteasome Inhibition Protects Astrocytes from Heme-mediated Oxidative Injury

Chen

Regan²

2005

CNR

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Hemin is released from hemoglobin after CNS hemorrhage, and may contribute to cell loss in surrounding tissue. Heme oxygenase-1 (HO-1) is induced by these injuries, and may have an effect on cell viability. In a prior study, we reported that increasing HO-1 expression by adenoviral gene transfer prior to hemin exposure attenuated oxidative stress and cell death in astrocytes. However, rapid gene transfer to the CNS may not be feasible. HO-1 expression is controlled by a stress-responsive transcription factor, Nrf2, which is a labile protein that is subject to proteasomal degradation. In this study, we hypothesized that preventing degradation of Nrf2 with a lipid-soluble proteasome inhibitor would increase HO-1 expression and protect astrocytes from hemin. Treatment of cortical astrocyte cultures with 1 microM MG-132 resulted in a rapid increase in Nrf2, to a level that was five-fold that of vehicle-treated cultures by 2 h. This was followed by a three to six-fold increase in HO-1 expression that persisted through the 16 h observation period. Exposure of cultures to 30 microM or 60 microM hemin for 8 h resulted in death, as measured by LDH release, of 39+/-3.0 or 67.5+/-5.9% of astrocytes. Pre-treatment with MG-132 prevented approximately half of this injury. Cytoprotection persisted at 24 h, and was also observed when injury was assessed via the MTT assay. Astrocyte protein oxidation produced by hemin was also significantly attenuated by MG-132 pre-treatment. These results suggest that increasing HO-1 expression with a proteasome inhibitor protects astrocytes from heme-mediated oxidative injury. This pharmacological approach may provide a mechanism for rapidly upregulating HO-1 in astrocytes after CNS hemorrhage.

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“…Numerosos estudios en animales han mostrado que estas células son especialmente vulnerables a muy diversos insultos, entre los que destaca la exposición a metales pesados (Hg, plomo, arsénico, cadmio y bismuto) ( [117][118][119][120][121][122][123] ), dañando sus receptores recaptadores de glutamato. La excesiva estimulación neuronal asociada a niveles elevados de glutamato intracerebrales aumenta la producción de especies reactivas de oxígeno, lo que a su vez induce estrés oxidativo, citotoxicidad y daño neuronal ( 124,125 ), razón por la que se ha postulado que, la exposición a metales pesados en fases muy tempranas de la vida, puede iniciar toda esta cadena de eventos que conducen, finalmente, a la muerte neuronal ( 126 ).…”

Section: Resultsunclassified