Metallothionein-Induced Increase in Mitochondrial Inner Membrane Permeability

Simpkins, Cuthbert O.; Lloyd, Tracy; Li, Sai; Balderman, Samuel C.

doi:10.1006/jsre.1997.5241

Cited by 28 publications

(18 citation statements)

References 21 publications

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“…Excess Zn 21 in mammalian cells is toxic, although a trace amount of Zn 21 serves as an effective antioxidant and a critical structural and functional component of zinc-binding proteins (40,41). Impaired mitochondrial function due to increased intracellular Zn 21 causes elevated intracellular ROS, leading to apoptotic or necrotic cell death (42)(43)(44). Recently, Nel and colleagues (30) reported that cytotoxicity of ZnO NPs may be directly related to dissolution of ZnO NPs suspended in bathing medium of RAW 264.7 and BEAS-2B cells, and Lin and colleagues (24) showed that viability of A549 cells is reduced in a dose-and time-dependent manner after apical exposure to ZnO NPs.…”

Section: Discussionmentioning

confidence: 99%

Alveolar Epithelial Cell Injury Due to Zinc Oxide Nanoparticle Exposure

Kim¹,

Fazlollahi²,

Kennedy³

et al. 2010

Am J Respir Crit Care Med

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Rationale: Although inhalation of zinc oxide (ZnO) nanoparticles (NPs) is known to cause systemic disease (i.e., metal fume fever), little is known about mechanisms underlying injury to alveolar epithelium. Objectives: Investigate ZnO NP-induced injury to alveolar epithelium by exposing primary cultured rat alveolar epithelial cell monolayers (RAECMs) to ZnO NPs. Methods: RAECMs were exposed apically to ZnO NPs or, in some experiments, to culture fluid containing ZnCl 2 or free Zn released from ZnO NPs. Transepithelial electrical resistance (R T ) and equivalent short-circuit current (I EQ ) were assessed as functions of concentration and time. Morphologic changes, lactate dehydrogenase release, cell membrane integrity, intracellular reactive oxygen species (ROS), and mitochondrial activity were measured. Measurements and Main Results: Apical exposure to 176 mg/ml ZnO NPs decreased R T and I EQ of RAECMs by 100% over 24 hours, whereas exposure to 11 mg/ml ZnO NPs had little effect. Changes in R T and I EQ caused by 176 mg/ml ZnO NPs were irreversible. ZnO NP effects on R T yielded half-maximal concentrations of approximately 20 mg/ml. Apical exposure for 24 hours to 176 mg/ml ZnO NPs induced decreases in mitochondrial activity and increases in lactate dehydrogenase release, permeability to fluorescein sulfonic acid, increased intracellular ROS, and translocation of ZnO NPs from apical to basolateral fluid (most likely across injured cells and/or damaged paracellular pathways). Conclusions: ZnO NPs cause severe injury to RAECMs in a dose-and time-dependent manner, mediated, at least in part, by free Zn released from ZnO NPs, mitochondrial dysfunction, and increased intracellular ROS.Keywords: epithelial monolayers; zinc toxicity; reactive oxygen species; mitochondrial damage; plasma membrane integrity Nanoparticles (NPs) are used in many commercial products and new applications in biomedicine, yet their fate, potential toxicity, and mechanisms of translocation in biological cells, tissues, and organs (including the lung) have not been well defined. Some, but not all, inhaled NPs (including ambient ultrafine particulates that overlap in size with NPs) have been reported to be associated with adverse health effects (1, 2). There is evidence that measurable amounts of these inhaled NPs are found in end organs (e.g., liver, spleen, and heart) after inhalation (3-6), possibly leading to thrombosis, atherogenesis, and cardiac dysrhythmias (3,7,8). NPs found in end organs after inhalation are most likely to enter the systemic circulation across the epithelia of the lung, especially the alveolar epithelium, which constitutes a very thin biological barrier (z0.5 mm) and affords greater than 95% of the surface area (z100 m 2 in humans) in distal airspaces of the lung.Of the NPs and ambient ultrafine particulates studied to date, several metal (e.g., Fe, Zn, V, and Ni) and metal oxide (Fe 2 O 3, ZnO, V 2 O 5 , and NiO) NPs have the potential to cause inflammation and injury in lungs (9-12). Among metal and metal oxide NPs i...

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Section: Discussionmentioning

confidence: 99%

Alveolar Epithelial Cell Injury Due to Zinc Oxide Nanoparticle Exposure

Kim¹,

Fazlollahi²,

Kennedy³

et al. 2010

Am J Respir Crit Care Med

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“…Metals have been reported in rats to damage mitochondrial membranes and increase their permeability (Garcia et al 2000;Belyaeva and Korotkov 2003;Belyaeva et al 2004). In addition, metallothionein, which is induced by cellular metal accumulation in several species including yellow perch (Giguère et al 2005), has also been reported to increase inner membrane permeability of rat mitochondria (Simpkins et al 1998). We do not know whether mitochondrial permeability is increased in metalcontaminated yellow perch, and if this would lead to compensatory increases in the activity of mitochondrial enzymes such as CS and CCO.…”

Section: Metal Effects On Metabolic Enzyme Activities and Longevitymentioning

confidence: 99%

Live Fast and Die Young: Metal Effects on Condition and Physiology of Wild Yellow Perch from along Two Metal Contamination Gradients

Couture¹,

Pyle

2008

Human and Ecological Risk Assessment: An International Journal

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This review summarizes some of the main findings of our work with the Metals in the Environment Research Network examining seasonal and regional effects on metal accumulation, growth, condition, and physiology in wild yellow perch (Perca flavescens) from 10 lakes comprising two metal contamination gradients in the industrial regions of Sudbury, Ontario and Rouyn-Noranda, Québec, Canada. The specific objectives of this review are: (1) to propose threshold tissue metal concentrations to discriminate between fish from contaminated and reference sites; (2) to identify factors that can influence metal accumulation and fish condition; and (3) to define an experimental approach for measuring metal effects in wild yellow perch. Using tissue thresholds appeared useful not only for discriminating fish from clean or contaminated environments, but also provided a simple approach to examine metabolic consequences of tissue metal accumulation. Overall, fish from Sudbury grew faster, expressed higher aerobic capacities, and died younger, but also appeared better at limiting accumulation of some metals than Rouyn-Noranda fish. The condition of the latter fish was clearly more affected by metals than Sudbury fish. Finally, our dataset allows us to propose that yellow perch are highly suitable for ecological risk assessment studies of metal effects in wild fish, but that fish size, season, and region must be considered in sampling design and that several reference sites must be studied for meaningful conclusions to be reached.

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“…Cigarettes made from tobacco grown in soil containing cadmium is another major source of cadmium intoxication [14] . In the blood, Cadmium stimulates the formation of metallothioneins [15] and Reactive Oxygen Species (ROS) thus causing oxidative damage in erythrocytes and in various tissues, which results in a loss of membrane functions [16] . Cadmium also induces the onset of anemia, decreases the red blood cell count, hemoglobin concentration and hematocrite value as well as reduced blood iron levels [17] .…”

Section: Introductionmentioning

confidence: 99%

Camel’s Milk Protects Against Cadmium Chloride-Induced Hypocromic Microcytic Anemia and Oxidative Stress in Red Blood Cells of White Albino Rats

Dallak¹

2009

American J. of Pharmacology and Toxicology

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Problem statement: Cadmium is a heavy metal of wide occupational and environmental contamination. In recent years, however, Cadmium has been implicated in the pathogenesis of several clinical disorders. One of the most frequently described problems in aluminum toxicity is anemia. Therefore, the present study was carried out to determine the effectiveness of Camel's milk in alleviating the toxicity of Aluminum Chloride (AlCl 3 ) on certain hematological parameters and antioxidant system components in the RBC's of white albino rats. Approach: Albino rats of both sexes (6/group) weighting between 230-250 g were divided into three treatment groups: Group one were rats given normal saline and served as control group, group two were rats treated with 2 mL of a solution containing cadmium chloride (10 mg kg −1 ) and named Cadmium chloride treated rats, group 3 were rat treated with 2 mL of a solution containing Camel's milk in which the same concentration of cadmium chloride was dissolved and named Camel's milk and Cadmium chloride treated rats. Rats were orally administered their respective doses every day for 21 days. Evaluations were made for hematological parameters in the blood and for oxidative stress components in the RBC's. Results: Results obtained showed that oral Cadmium chloride treatment caused a significant decrease in total red blood cell counts, Hematocrite (PCV) value, Hemoglobin (Hb) concentration, Meancorpuscular Volume (MVC), Mean Hemoglobin Concentration (MHC) and Mean Corpuscular Hemoglobin Concentration (MCHC). Also oral administration of Cadmium chloride induced free radicals and as a result caused a significant decrease in the activities of Superoxide Dismutase (SOD), Catalsae (CAT) and reduced glutathione (SGH) in the RBCs homolysate. The oral administration of Camel's milk with cadmium chloride alleviated it's toxic effect. Camel's milk administration resulted in a significant increase in the in total erythrocytes count, blood Hb, PCV, MCV, MHC and MCHC. Camel's milk reduced free radicals production and oxidative stress status in the RBC's noticed by the significant increased activities of SOD and CAT, as well as concentrations reduced glutathione (SGH). Conclusion: The above results indicated a protective effect of camel's milk oral administration against cadmium induced anemia and oxidative stress in the RBC's of white albino rats.

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Metallothionein-Induced Increase in Mitochondrial Inner Membrane Permeability

Cited by 28 publications

References 21 publications

Alveolar Epithelial Cell Injury Due to Zinc Oxide Nanoparticle Exposure

Alveolar Epithelial Cell Injury Due to Zinc Oxide Nanoparticle Exposure

Live Fast and Die Young: Metal Effects on Condition and Physiology of Wild Yellow Perch from along Two Metal Contamination Gradients

Camel’s Milk Protects Against Cadmium Chloride-Induced Hypocromic Microcytic Anemia and Oxidative Stress in Red Blood Cells of White Albino Rats

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