Subchronic Toxicity of Cupric Sulfate Administered in Drinking Water and Feed to Rats and Mice

Hébert, Charles; Elwell, Michael R.; Travlos, Gregory S.; Fitz, Chad; Bucher, John R.

doi:10.1093/toxsci/21.4.461

Cited by 12 publications

(7 citation statements)

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“…Decreased body weight gain in rats and mice fed high-copper diets was attributed to reduced food consumption (13). Such a decrease in body weight gain was also noted in our CUE group, although we did not measure the food intake.…”

Section: Morphologic Evaluation Of Darnagesupporting

confidence: 56%

Analysis of Lung Damage Induced by Trichloroethylene Inhalation in Mice Fed Diets with Low, Normal, and High Copper Content

Giovanetti¹,

Rossi

Mancuso³

et al. 1998

Toxicol Pathol

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Copper is both an essential nutrient required for the activity of several enzymes and a toxic element able to catalyze free radical formation. Trichloroethylene (TCE) is a xenobiotic that generates epoxidic intermediates by bioactivation through the cytochrome P-450 system. In this study, the influence of a dietary copper imbalance on the TCE-induced lung damage was investigated. Weaning mice were fed copper-deficient, copper-sufficient, and copper-excessive diets. After 4 wk, mice were exposed for 30 min to 6,500 ppm of TCE and euthanatized 48 hr later. Lung damage in the TCE-treated mice consisted of vacuolations of Clara cells and was quantitatively evaluated by counting the vacuolated cells per micrometer of basal lamina. At the ultrastructural level, vacuolations appeared as the result of hydropic swelling of the endoplasmic reticulum cisternae. The copper-deficient mice presented the highest number of vacuolated Clara cells. These mice also showed alteration of the capillary endothelium and interstitium and decreased pulmonary copper-zinc-superoxide dismutase activity. Occurrence of oxidative stress in lungs of both copper-sufficient and copper-deficient mice following TCE treatment was indicated by a decrease in reduced glutathione and an increase in its oxidized form.

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Section: Morphologic Evaluation Of Darnagesupporting

confidence: 56%

Analysis of Lung Damage Induced by Trichloroethylene Inhalation in Mice Fed Diets with Low, Normal, and High Copper Content

Giovanetti¹,

Rossi

Mancuso³

et al. 1998

Toxicol Pathol

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“…Other scientists also observed similar finding where they found destruction of RBCs in rodents that cause anaemia and reducing RBCs count, HCT, MCH, HB, MCV and WBCs (leukocytes) [119, 120]. Moreover, higher level of Cu prevents absorption and utilisation of iron hence level of iron reduces and eventually diminishes in the serum [121, 122]. These findings demonstrate that CuO NPs disturb RBCs count and immune system of the treated organism.…”

Section: Biochemical Alterations Induced By Cuo Npsmentioning

confidence: 56%

Toxicity of copper oxide nanoparticles: a review study

Naz

Gul

Zia³

2019

IET nanobiotechnol.

231

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Copper oxide nanoparticles (CuO NPs) use has exponentially increased in various applications (such as industrial catalyst, gas sensors, electronic materials, biomedicines, environmental remediation) due to their flexible properties, i.e. large surface area to volume ratio. These broad applications, however, have increased human exposure and thus the potential risk related to their short-and long-term toxicity. Their release in environment has drawn considerable attention which has become an eminent area of research and development. To understand the toxicological impact of CuO NPs, this review summarises the in-vitro and in-vivo toxicity of CuO NPs subjected to species (bacterial, algae, fish, rats, human cell lines) used for toxicological hazard assessment. The key factors that influence the toxicity of CuO NPs such as particle shape, size, surface functionalisation, time-dose interaction and animal and cell models are elaborated. The literature evidences that the CuO NPs exposure to the living systems results in reactive oxygen species generation, oxidative stress, inflammation, cytotoxicity, genotoxicity and immunotoxicity. However, the physio-chemical characteristics of CuO NPs, concentration, mode of exposure, animal model and assessment characteristics are the main perspectives that define toxicology of CuO NPs.

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“…Copper is oxidized and detoxified by the ceruloplasmin carrier. We saw no evidence of abnormal copper deposition in organs or any findings consistent with copper-induced toxicity; for example, no evidence of hepatic inflammation in rats at tolerated doses with green serum, absence of increased cytoplasmic eosinophilic globules in renal proximal tubular epithelial cells, and no evidence of hyperplastic/hyperkeratotic areas of gastric mucosa (Hebert et al 1993). In addition, we did not observe heart-related microscopic changes or neurological-related adverse clinical signs in our rat studies (which have been postulated as potential risks for humans with increased circulating ceruloplasmin; Dadu et al 2013; Tombini et al 2013).…”

Section: Discussionmentioning

confidence: 90%

MEK and ERK Kinase Inhibitors Increase Circulating Ceruloplasmin and Cause Green Serum in Rats

Diaz¹,

Pai²,

Cain³

et al. 2016

Toxicol Pathol

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Inhibition of the mitogen-activated protein kinase/extracellular signal-regulated (MAPK/ERK) pathway is an attractive therapeutic approach for human cancer therapy. In the course of evaluating structurally distinct small molecule inhibitors that target mitogen-activated protein kinase kinase (MEK) and ERK kinases in this pathway, we observed an unusual, dose-related increase in the incidence of green serum in preclinical safety studies in rats. Having ruled out changes in bilirubin metabolism, we demonstrated a 2- to 3-fold increase in serum ceruloplasmin levels, likely accounting for the observed green color. This was not associated with an increase in α-2-macroglobulin, the major acute phase protein in rats, indicating that ceruloplasmin levels increased independently of an inflammatory response. Elevated serum ceruloplasmin was also not correlated with changes in total hepatic copper, adverse clinical signs, or pathology findings indicative of copper toxicity, therefore discounting copper overload as the etiology. Both ERK and MEK inhibitors led to increased ceruloplasmin secretion in rat primary hepatocyte cultures in vitro, and this increase was associated with activation of the Forkhead box, class O1 (FOXO1) transcription factor. In conclusion, increased serum ceruloplasmin induced by MEK and ERK inhibition is due to increased synthesis by hepatocytes from FOXO1 activation and results in the nonadverse development of green serum in rats.

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Subchronic Toxicity of Cupric Sulfate Administered in Drinking Water and Feed to Rats and Mice

Cited by 12 publications

References 0 publications

Analysis of Lung Damage Induced by Trichloroethylene Inhalation in Mice Fed Diets with Low, Normal, and High Copper Content

Analysis of Lung Damage Induced by Trichloroethylene Inhalation in Mice Fed Diets with Low, Normal, and High Copper Content

Toxicity of copper oxide nanoparticles: a review study

MEK and ERK Kinase Inhibitors Increase Circulating Ceruloplasmin and Cause Green Serum in Rats

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