Delayed Apoptosis Post-Cadmium Injury in Renal Proximal Tubule Epithelial Cells

Stinson, Lindsay J; Darmon, Alison J.; Dagnino, Lina; D’Souza, Sudhir J.A.

doi:10.1159/000066298

Cited by 16 publications

(10 citation statements)

References 34 publications

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“…In previous studies (McAmis et al 2003;Wolf & Baynes 2006), we found that the anticancer quinones depleted ATP and caused a barrier dysfunction. In other studies, mercury caused ATP depletion along with barrier dysfunction (Toimela et al 2004) and cadmium caused ATP depletion and increased permeability in renal epithelial cells (Stinson et al 2003). These changes may have just been simultaneous occurrences, but the sulfhydryl reagent, iodoacetate, depletes ATP prior to the appearance of a barrier dysfunction in EC (Wilson et al 1990).…”

Section: Discussionmentioning

confidence: 95%

Cadmium and mercury cause an oxidative stress-induced endothelial dysfunction

Wolf

Baynes

2006

Biometals

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We investigated the ability of cadmium and mercury ions to cause endothelial dysfunction in bovine pulmonary artery endothelial cell monolayers. Exposure of monolayers for 48 h to metal concentrations greater than 3-5 microM produced profound cytotoxicity (increased lactate dehydrogenase leakage), a permeability barrier failure, depletion of glutathione and ATP and almost complete inhibition of the activity of key thiol enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In contrast, metal concentrations less than 1-2 microM induced increases in glutathione and thiol-enzyme activities with minimal changes in LDH leakage, barrier function and ATP content. At shorter incubation times (24 h or less), high concentrations of cadmium caused glutathione induction rather than depletion. Thus, oxidative stress and cytotoxicity induced by lower concentrations of the metal ions stimulate compensatory responses, including increased synthesis of glutathione, which presumably preserved the activity of key thiol enzymes, however these responses were not sustainable at higher metal ion concentrations. We conclude, while high concentrations of heavy metals are cytotoxic, lower concentration induce a compensatory protective response, which may explain threshold effects in metal-ion toxicity.

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Section: Discussionmentioning

confidence: 95%

Cadmium and mercury cause an oxidative stress-induced endothelial dysfunction

Wolf

Baynes

2006

Biometals

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“…CdCl 2 causes reactive oxidation by increasing the intracellular glutathione, resulting in apoptosis [11,29]. Cytochrome-C is released as a result of mitochondrial swelling.…”

Section: Resultsmentioning

confidence: 99%

“…Cadmium exposure results in necrotic and apoptotic cell death [10]. While some 25% of renal proximal tubular epithelium undergo necrosis, 25-50% of them go through apoptosis [11]. The principal target of cadmium is renal proximal tubules.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural Changes in the Kidney of Rats with Acute Exposure to Cadmium and Effects of Exogenous Metallothionein

Kükner

Çolakoğlu

Kara

et al. 2007

Biol Trace Elem Res

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Ultrastructural changes in the kidneys of rats after acute cadmium exposure and the effects of exogenous metallothionein (MT) were studied by transmission electron microscopy. Thirty-six adult Wistar rats were divided into three groups. Cadmium chloride (CdCl2) (3.5 mg/kg/day) was injected subcutaneously in the first group. In the second group, 30 micromol/kg MT was administered in addition to CdCl2. Control rats received 0.5 ml subcutaneous saline solution. Four rats from each group were killed on days 1, 3, 5, and 7 after administration of the compounds. Kidney tissues were taken and fixed in 2.5% glutaraldehyde solution for electron microscopic observations. Tissue damage in kidney increased as time passed since the administration of CdCl2 in the first group. Degeneration in the proximal and distal tubules was observed. Increased apoptosis was seen in the proximal tubules epithelium, especially on day 7. Peritubular capillaries became dilated, there was degeneration of the endothelial cells, and the amount of intertubular collagen fibers was increased. On day 1, irregular microvilli in the proximal tubules, deepening of the basal striations, and myelin figures; on day 3, multiple vesicular mitochondria and regions of edema around tubules; on days 5 and 7, increased apoptotic cell in the proximal tubules and widened rough endoplasmic reticulum of the endothelial cells of glomerular capillaries were observed. We observed that the structural alterations that increased depending on the day of Cd administration decreased after exogenous MT administration, the dilation of the peritubular capillaries persisted, and there were degenerated proximal tubules. It was established that cadmium chloride was toxic for kidney cortex and caused structural damage. Exogenous MT partly prevents CdCl2-induced damage.

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“…Cadmium induces cellular damage through several mechanisms, one of the best characterized is that it accumulates in mitochondria, where it blocks the respiratory chain at complex III resulting in an increased production of free radicals that enhances caspase activity leading to apoptosis [27]. Free Cd also binds to chemical functional groups in several proteins.…”

Section: Nephrotoxicity Of Heavy Metals On Tjsmentioning

confidence: 99%

Tight Junction Proteins and Oxidative Stress in Heavy Metals-Induced Nephrotoxicity

Reyes

Molina‐Jijón

Rodríguez-Muñóz

et al. 2013

BioMed Research International

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Kidney is a target organ for heavy metals. They accumulate in several segments of the nephron and cause profound alterations in morphology and function. Acute intoxication frequently causes acute renal failure. The effects of chronic exposure have not been fully disclosed. In recent years increasing awareness of the consequences of their presence in the kidney has evolved. In this review we focus on the alterations induced by heavy metals on the intercellular junctions of the kidney. We describe that in addition to the proximal tubule, which has been recognized as the main site of accumulation and injury, other segments of the nephron, such as glomeruli, vessels, and distal nephron, show also deleterious effects. We also emphasize the participation of oxidative stress as a relevant component of the renal damage induced by heavy metals and the beneficial effect that some antioxidant drugs, such as vitamin A (all-trans-retinoic acid) and vitamin E (α-tocopherol), depict on the morphological and functional alterations induced by heavy metals.

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Delayed Apoptosis Post-Cadmium Injury in Renal Proximal Tubule Epithelial Cells

Cited by 16 publications

References 34 publications

Cadmium and mercury cause an oxidative stress-induced endothelial dysfunction

Cadmium and mercury cause an oxidative stress-induced endothelial dysfunction

Ultrastructural Changes in the Kidney of Rats with Acute Exposure to Cadmium and Effects of Exogenous Metallothionein

Tight Junction Proteins and Oxidative Stress in Heavy Metals-Induced Nephrotoxicity

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