Metallothionein Induction and Pulmonary Responses to Inhaled Cadmium Chloride in Rats and Mice

Kenaga, C.; Cherian, M. George; Cox, Christopher; Oberdörster, Günter

doi:10.1006/faat.1996.0057

Cited by 21 publications

(2 citation statements)

References 19 publications

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“…Studies of metal-binding proteins such as ALAD and metallothioneins that influence lead absorption, and thus its neurotoxicity, have been modeled in mice (Gonick, 2011). Furthermore, studies have suggested that metallothioneins and ALAD dynamics in mice are highly comparable to those in humans (Gonick, 2011; Kenaga, Cherian, Cox, and Oberdorster, 1996; Takahashi, 2012) suggesting the value of a mouse model for understanding the effects of chronic low-level lead exposure on behavior. For future studies, it may be useful to consider briefly a few possible mechanistic sources of the behavioral differences observed.…”

Section: Discussionmentioning

confidence: 99%

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

Flores-Montoya

Sobin

2014

J of Applied Toxicology

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Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 μg dl−1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 μg dl−1.

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Section: Discussionmentioning

confidence: 99%

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

Flores-Montoya

Sobin

2014

J of Applied Toxicology

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“…Between 7 and 40 percent of inhaled cadmium will be taken up into blood; the higher percentages are valid for soluble cadmium compounds and nanopariculate cadmium, for example, in cigarette smoke [19]. Cd binds to MT in lung tissue and MT is induced by Cd exposure [20]. Binding to MT modifies the toxic effects in pulmonary tissues.…”

Section: Uptakementioning

confidence: 99%

Metallothionein and Cadmium Toxicology—Historical Review and Commentary

Nordberg

2022

Biomolecules

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More than one and a half centuries ago, adverse human health effects were reported after use of a cadmium-containing silver polishing agent. Long-term cadmium exposure gives rise to kidney or bone disease, reproductive toxicity and cancer in animals and humans. At present, high human exposures to cadmium occur in small-scale mining, underlining the need for preventive measures. This is particularly urgent in view of the growing demand for minerals and metals in global climate change mitigation. This review deals with a specific part of cadmium toxicology that is important for understanding when toxic effects appear and, thus, is crucial for risk assessment. The discovery of the low-molecular-weight protein metallothionein (MT) in 1957 was an important milestone because, when this protein binds cadmium, it modifies cellular cadmium toxicity. The present authors contributed evidence in the 1970s concerning cadmium binding to MT and synthesis of the protein in tissues. We showed that binding of cadmium to metallothionein in tissues prevented some toxic effects, but that metallothionein can increase the transport of cadmium to the kidneys. Special studies showed the importance of the Cd/Zn ratio in MT for expression of toxicity in the kidneys. We also developed models of cadmium toxicokinetics based on our MT-related findings. This model combined with estimates of tissue levels giving rise to toxicity, made it possible to calculate expected risks in relation to exposure. Other scientists developed these models further and international organizations have successfully used these amended models in recent publications. Our contributions in recent decades included studies in humans of MT-related biomarkers showing the importance of MT gene expression in lymphocytes and MT autoantibodies for risks of Cd-related adverse effects in cadmium-exposed population groups. In a study of the impact of zinc status on the risk of kidney dysfunction in a cadmium-exposed group, the risks were low when zinc status was good and high when zinc status was poor. The present review summarizes this evidence in a risk assessment context and calls for its application in order to improve preventive measures against adverse effects of cadmium exposures in humans and animals.

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Metallothionein induction in the liver, kidney, heart and aorta of cadmium and isoproterenol treated rats

Bobillier-Chaumont¹,

Maupoil²,

Berthelot³

2005

J. Appl. Toxicol.

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Metallothionein (MT), induced in different organs in response to heavy metals and oxidative conditions, exerts antioxidant properties and thus could be implicated in cardiovascular physiopathology. The aim of this study was to investigate the capacity of cadmium (Cd) and isoproterenol to induce in vivo MT not only in rat liver and kidneys but also in heart and aorta. Tissue MT levels, catalase (CAT) and glutathione peroxidase (GPX) activities were assayed at different times after Cd or isoproterenol injection. Cd induced a dose-dependent induction of MT with a higher response in the liver than in the kidney, aorta and heart. The hepatic increase was early (12 h) and maintained (72 h), whereas the elevation was maximal around 48 h for the other organs. Isoproterenol induced a transient (12 h) hepatic and a biphasic (12 and 36 h) renal and cardiac increase. CAT activity was decreased in the liver and increased in the heart with the higher Cd doses. Isoproterenol increased the cardiac GPX activity. In conclusion, the results demonstrate that MT can be induced in rat liver and kidneys but also in heart after a Cd or isoproterenol injection. This enhancement of cardiac and vascular MT levels could be used to study the potential protective effect of MT in cardiovascular diseases.

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Metallothionein Induction and Pulmonary Responses to Inhaled Cadmium Chloride in Rats and Mice

Cited by 21 publications

References 19 publications

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

Metallothionein and Cadmium Toxicology—Historical Review and Commentary

Metallothionein induction in the liver, kidney, heart and aorta of cadmium and isoproterenol treated rats

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