Stressor: 335

Title

To create a new stressor, from the Listing Stressors page at https://aopwiki.org/stressors click ‘New stressor.’ This will bring you to a page entitled “New Stressor” where a stressor title can be entered. Click ‘Create stressor’ to create a new Stressor page listing the stressor title at the top. More help

Cadmium

Stressor Overview

The stressor field is a structured data field that can be used to annotate an AOP with standardised terms identifying stressors known to trigger the MIE/AOP. Most often these are chemical names selected from established chemical ontologies. However, depending on the information available, this could also refer to chemical categories (i.e., groups of chemicals with defined structural features known to trigger the MIE). It can also include non-chemical stressors such as genetic or environmental factors. More help

AOPs Including This Stressor

This table is automatically generated and lists the AOPs associated with this Stressor. More help

Events Including This Stressor

This table is automatically generated and lists the Key Events associated with this Stressor. More help

Chemical Table

The Chemical Table lists chemicals associated with a stressor. This table contains information about the User’s term for a chemical, the DTXID, Preferred name, CAS number, JChem InChIKey, and Indigo InChIKey.To add a chemical associated with a particular stressor, next to the Chemical Table click ‘Add chemical.’ This will redirect you to a page entitled “New Stressor Chemical.’ The dialog box can be used to search for chemical by name, CAS number, JChem InChIKey, and Indigo InChIKey. Searching by these fields will bring forward a drop down list of existing stressor chemicals formatted as  Preferred name, “CAS- preferred name,” “JChem InChIKey – preferred name,” or “Indigo InChIKey- preferred name,” depending on by which field you perform the search. It may take several moments for the drop down list to display. Select an entity from the drop down list and click ‘Add chemical.’ This will return you to the Stressor Page, where the new record should be in the ‘Chemical Table’ on the page.To remove a chemical associated with a particular stressor, in the Chemical Table next to the chemical you wish to delete, click ‘Remove’ and then click 'OK.' The chemical should no longer be visible in the Chemical table. More help
User term DTXID Preferred name Casrn jchem_inchi_key indigo_inchi_key
Cadmium DTXSID1023940 Cadmium 7440-43-9 BDOSMKKIYDKNTQ-UHFFFAOYSA-N BDOSMKKIYDKNTQ-UHFFFAOYSA-N

AOP Evidence

This table is automatically generated and includes the AOPs with this associated stressor as well as the evidence term and evidence text from this AOP Stressor. More help

Event Evidence

This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor. More help
Cystic Fibrosis Transmembrane Regulator Function, Decreased

Cadmium (Cd) decreased CFTR protein expression in Calu-3 cells in a dose- and time-dependent manner. CFTR transcript levels, however, appeared to only be transiently affected. Reduced CFTR expression at the plasma membrane was associated with a reduction in CFTR Cl conductance. Treatment of cells with NAC did not rescue CFTR expression in Cd-treated cells. In contrast, co-treatment with α-tocopherol prevented CFTR inhibition, and this effect was linked to α-tocopherol suppressing the accumulation of ubiquitinated CFTR (Rennolds et al., 2010).

Inhibition, Mitochondrial Electron Transport Chain Complexes

Mitochondrial electron transport chain impairment by cadmium occurs through its binding or its transport through the selectively permeable inner mitochondrial membrane to harm structures involved in oxidative phosphorylation (Adiele et al., 2012). Specifically, Wang et al. (2004) showed that CIII inhibition by cadmium is not related to the binding of Cd to the substrate binding sites, but rather to it binding allosterically to the Qo site of CIII. The binding of Cd prevents electron delivery from semiubiquinone to heme b566 and promotes the accumulation of semiubiquinone at the Qo site. The accumulated semiubiquinone is unstable and prone to donation of electrons to molecular oxygen, thus forming superoxide anion (Wang et al., 2004).

Cd-dependent inhibition of CIII was determined in the presence of excess zinc, which has been shown to bind to the Qo site of CIII and inhibit electron transfer activity (Wang et al., 2004). Double reciprocal plots for Zn inhibition of cytochrome c reductase (CIII) activity in the absence and presence of Cd showed that the Vmax values were not changed, indicating competition between Cd and Zn for the same binding site in CIII (Qo) (Wang et al., 2004).

Wang et al. (2004) measured the effects of Cd on the enzyme activity of CIII in the mitochondria of liver, brain, and heart, and determined that maximum inhibition was 30-77%. Adiele et al. (2012) found a maximum of 65% inhibition of CIII enzyme activity by Cd during state 3 mitochondrial respiration, and 75% inhibition of ATP production by Cd compared to the control in rainbow trout liver mitochondria.

Increase, Oxidative Stress

Belyaeva et al. (2012) investigated the effect of cadmium treatment on human kidney cells. They found that cadmium was the most toxic when the sample was treated with 500 μM for 3 hours (Belyaeva et al., 2012). As this study also looked at mercury, it is worth noting that mercury was more toxic than cadmium in both 30-minute and 3-hour exposures at low concentrations (10-100 μM) (Belyaeva et al., 2012).

Wang et al. (2009) conducted a study evaluating the effects of cadmium treatment on rats and found that the treated group showed a significant increase in lipid peroxidation. They also assessed the effects of lead in this study, and found that cadmium can achieve a very similar level of lipid peroxidation at a much lower concentration than lead can, implying that cadmium is a much more toxic metal to the kidney mitochondria than lead is (Wang et al., 2009). They also found that when lead and cadmium were applied together they had an additive effect in increasing lipid peroxidation content in the renal cortex of rats (Wang et al., 2009).

Jozefczak et al. (2015) treated Arabidopsis thaliana wildtype, cad2-1 mutant, and vtc1-1 mutant plants with cadmium to determine the effects of heavy metal exposure to plant mitochondria in the roots and leaves. They found that total GSH/GSG ratios were significantly increased after cadmium exposure in the leaves of all sample varieties and that GSH content was most significantly decreased for the wildtype plant roots (Jozefczak et al., 2015).

Andjelkovic et al. (2019) also found that renal lipid peroxidation was significantly increased in rats treated with 30 mg/kg of cadmium.

Oxidative Stress

Belyaeva et al. (2012) investigated the effect of cadmium treatment on human kidney cells. They found that cadmium was the most toxic when the sample was treated with 500 μM for 3 hours (Belyaeva et al., 2012). As this study also looked at mercury, it is worth noting that mercury was more toxic than cadmium in both 30-minute and 3-hour exposures at low concentrations (10-100 μM) (Belyaeva et al., 2012).

Wang et al. (2009) conducted a study evaluating the effects of cadmium treatment on rats and found that the treated group showed a significant increase in lipid peroxidation. They also assessed the effects of lead in this study, and found that cadmium can achieve a very similar level of lipid peroxidation at a much lower concentration than lead can, implying that cadmium is a much more toxic metal to the kidney mitochondria than lead is (Wang et al., 2009). They also found that when lead and cadmium were applied together they had an additive effect in increasing lipid peroxidation content in the renal cortex of rats (Wang et al., 2009).

Jozefczak et al. (2015) treated Arabidopsis thaliana wildtype, cad2-1 mutant, and vtc1-1 mutant plants with cadmium to determine the effects of heavy metal exposure to plant mitochondria in the roots and leaves. They found that total GSH/GSG ratios were significantly increased after cadmium exposure in the leaves of all sample varieties and that GSH content was most significantly decreased for the wildtype plant roots (Jozefczak et al., 2015).

Andjelkovic et al. (2019) also found that renal lipid peroxidation was significantly increased in rats treated with 30 mg/kg of cadmium.

Increase, Cytotoxicity (renal tubular cell)

Belyaeva et al. (2012) investigated the effects of cadmium on cell viability of human kidney cells. When they observed the release of lactate dehydrogenase (LDH) after different incubation times they found that the kidney cells treated with 500 μM of cadmium released significant LDH (Belyaeva et al. 2012). Belyaeva et al. (2012) also looked at the LDH release in kidney cells treated with mercury and found that mercury treatment was more toxic than cadmium treatment, as it showed significant LDH release at a lower dosage of treatment.

Hinkle et al. (1987) treated rat pituitary gland neoplasm cells with cadmium to assess the cytotoxicity of the heavy metal treatment. Their results showed a dose-dependant decrease in association with cadmium treatment up to 15 μM (Hinkle et al., 1987).

In their study of the effects of cadmium treatment on human embryonic kidney cells, Chomchan et al. (2018) determined that cadmium treatment caused a dose-dependant decrease in cell viability when treating cells with 0 to 100 μM. The IC50 value determined in this study was 68.50 μg/mL (Chomchan et al., 2018).

Mezynska et al. (2019) treated rats with cadmium and observed the cytotoxicity of the liver. They found that the lipid peroxides (LPO) released by the treated cells was significantly increased as early as 3 months into 1 mg/kg treatment and was the highest at 10 months (Mezynska et al., 2019). When treated with 5 mg/kg of cadmium treatment was significant as early as 3 months and was the most affected at 10 months (Mezynska et al., 2019).

N/A, Mitochondrial dysfunction 1

Belyaeva et al. (2012) studied the effects of cadmium treatment on rat kidney cells. In particular, they looked at different respiration rates in treated and untreated rat kidney cell lines. They found that resting respiration rates were significantly stimulated at 48 hours of treatment with 100 µM of cadmium, while uncoupled respiration was unaffected, and basal respiration was enhanced (Belyaeva et al., 2012). These changes in respiration imply that cadmium was capable of reducing the uncoupling efficiency of the cells at concentrations of 100 µM or higher.

Miccadei and Floridi (1993) studied changes in oxygen consumption in rat liver mitochondria which had been treated with cadmium. Their results showed that the treated rats showed a dose-dependant decrease in oxygen consumption which began with doses as low as 3 µM (Miccadei and Floridi, 1993).

Wang et al. (2009), found that, when applied together, lead and cadmium showed individual inhibition and additive effects of rat kidney mitochondrial COX gene expression.

Stressor Info

Text sections under this subheading include the Chemical/Category Description and Characterization of Exposure. More help
Chemical/Category Description
To edit the Chemical/Category Description” section, on a KER page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “Chemical/Category Description” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “Chemical/Category Description”  section on the page. More help
Characterization of Exposure
To edit the “Characterization of Exposure” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “Characterization of Exposure”  section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “Characterization of Exposure” section on the page. More help

References

List of the literature that was cited for this Stressor description. Ideally, the list of references, should conform, to the extent possible, with the OECD Style Guide (https://www.oecd.org/about/publishing/OECD-Style-Guide-Third-Edition.pdf) (OECD, 2015).To edit the “References” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “References” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “References” section on the page. More help