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Event: 1969

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increase, Oxidative Stress

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Increase, Oxidative Stress
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Inhibition of Mt-ETC complexes leading to kidney toxicity KeyEvent Agnes Aggy (send email) Under development: Not open for comment. Do not cite Under Development
Succinate dehydrogenase inhibition leading to increased insulin resistance KeyEvent Evgeniia Kazymova (send email) Under development: Not open for comment. Do not cite
AhR activation in the thyroid leading to Adverse Neurodevelopmental Outcomes in Mammals KeyEvent Brendan Ferreri-Hanberry (send email) Under development: Not open for comment. Do not cite
Vascular disrupting effects KeyEvent Brendan Ferreri-Hanberry (send email) Under development: Not open for comment. Do not cite
The inhibition of Nrf2 leading to vascular disrupting effects KeyEvent Agnes Aggy (send email) Under development: Not open for comment. Do not cite
Demethylation of PPAR promotor leading to vascular disrupting effects KeyEvent Allie Always (send email) Under development: Not open for comment. Do not cite
The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects KeyEvent Evgeniia Kazymova (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

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Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

“Oxidative stress is traditionally defined as an imbalance between production of ROS and endogenous antioxidants” (Small et al., 2018). Reactive Oxygen Species (ROS), the core perpetrators of oxidative stress, are highly reactive free radical oxygen molecules (Turrens, 2003; Valko et al., 2005; Hancock et al., 2001). These free radicals are strong oxidants that in high amounts, could irreversibly damage the cell and its organelles. ROS, however, are not by default detrimental to cellular function but contribute to normal activities, under physiological conditions. Reactive oxygen species can behave as signaling molecules by oxidizing proteins, lipids, and polynucleotides (Zhao et al., 2019; Hancock et al., 2001; Gorlach et al., 2015). When present in tolerable amounts, superoxides (O2-) behave as signalling molecules important in cell proliferation, hypoxia adaption, and cell fate determination but when present in excess or unregulated, induce cell damage and death (Zhao et al., 2019). Under normal oxidative phosphorylation, approximately 1-2% of the oxygen reduced by mitochondria converts into reactive oxygen species (ROS) at intermediate steps of the respiratory chain, during electron transfer (Kowaltowski and Vercesi, 1998; Volka et al., 2005; Li et al., 2003). On top of ROS generation occurring during natural cell metabolism, several other mitochondrial enzymes, such as cytochrome P450, are linked to ROS production and, interestingly many of these systems are modulated by calcium (Gorlach et al., 2015; Hancock et al., 2001). The main reasons that these antioxidant systems are in place are to regulate the constant, regular production of ROS and their signalling functionality. Oxidative stress is defined as a disruption of the pro-oxidant-antioxidant balance, favouring pro-oxidants, potentially damaging cellular components (Sies, 1991). It is important to note the fact that oxidative stress is generally caused by one of three reasons: either there is a significant increase in ROS; or there is a significant decrease in antioxidant function; or the two factors working in tandem. This distinction is crucial in determining methods of assessment of oxidative stress.

Other than mitochondrial ROS production, one of the primary producers of superoxide (O2-) is NADPH, doing so by a single electron reduction of molecular oxygen (Panday et al., 2014). NADPH oxidase, is a cytosolic-membrane protein, implicated in host defence, cellular signalling, and gene expression regulation. It is thought to produce ROS partly for defence against microbial pathogens (Panday et al., 2014). Due to its volatile nature, once formed, O2 released into the inter-membrane space (IMS) by CIII inevitably generates hydrogen peroxide (H2O2), a reaction is catalyzed by superoxide dismutase (SOD) (Hancock et al., 2001). Once present, the fate of H2O2 is variable and its reduction to H2O can be catalyzed by glutathione peroxidase (GPx) or peroxisomal catalase. Otherwise, it can be further converted into highly reactive hydroxyl radicals, particularly in the presence of metal ions (Hancock et al., 2001; Valko et al., 2005; Adam-Vizi et al., 2010).

Under normal mitochondrial conditions, antioxidant enzymes and molecules – such as, superoxide dismutase, glutathione peroxidase, catalase, and glutathione – balance ROS generation by scavenging or binding to ROS (Santos et al., 2007). ROS disposal involves superoxide dismutase (SOD) converting O2- to H2O2, then detoxified into H2O by glutathione and catalase (Xu & Møller, 2010). Also, in case of mitochondrial damage or dysfunction, the antioxidant defence system may be impaired and its capacity drops. The resultant imbalance of the production and removal of ROS is oxidative stress. Due to the nature of oxidative stress induction and the short half-life of ROS, measuring oxidative stress through antioxidant function is a more accurate and effective way to determine the state of the cell. Oxidative stress behaves as a positive feedback loop, leading to the over-production of free-radicals as ROS further damage the mitochondria and antioxidant capacity continues to decrease (Hancock et al., 2001; Turrens, 2003; Valko et al., 2005). Antioxidant defenses can also be inhibited, further contributing to mitochondrial dysfunction; this is commonly induced by exposure to heavy metals (Blajszczak and Bonini, 2017). Due to the formation of this positive feedback loop, we experience a gap in knowledge as to which event initiated the cycle; was the increased ROS production the cause of mitochondrial dysfunction or did the mitochondrial dysfunction lead to increased ROS production?

Heavy metal exposure in aerobic organisms increases ROS formation through redox cycling, where metals with different valence states (for example Fe, Cu, and Cr) directly produce ROS as they are reduced by cellular antioxidants and then react with oxygen (Shaki et al., 2012; Shaki et al., 2013; Pourahmad et al., 2006; Santos et al., 2007). The production of highly reactive hydroxyl radicals under mitochondrial oxidative stress in the presence of transition metals occurs via the Fenton reaction or Haber-Weiss reaction (Hancock et al., 2001; Valko et al., 2005; Adam-Vizi et al., 2010). Metals have been shown to inhibit ROS-detoxifying enzymes. By binding to these enzymes, metals can inhibit their antioxidant functions, and cause an accumulation of ROS and increased synthesis of more antioxidants in order to combat the oxidative stress (Blajszczak and Bonini, 2017).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help


Assay Type & Measured Content Description Dose Range Studied

Assay Characteristics (Length / Ease of use/Accuracy)

ROS Formation in the Mitochondria assay


(Shaki et al., 2012)

“The mitochondrial ROS measurement was performed flow cytometry using DCFH-DA. Briefly, isolated kidney mitochondria were incubated with UA (0, 50, 100 and 200 μM) in respiration buffer containing (0.32 mM sucrose, 10 mM Tris, 20 mM Mops, 50 μM EGTA, 0.5 mM MgCl2, 0.1 mM KH2PO4 and 5 mM sodium succinate) [32]. In the interval times of 5, 30 and 60 min following the UA addition, a sample was taken and DCFH-DA was added (final concentration, 10 μM) to mitochondria and was then incubated for 10 min. Uranyl acetate-induced ROS generation in isolated kidney mitochondria were determined through the flow cytometry (Partec, Deutschland) equipped with a 488-nm argon ion laser and supplied with the Flomax software and the signals were obtained using a 530-nm bandpass filter (FL-1 channel). Each determination is based on the mean fluorescence intensity of 15,000 counts.” (Shaki et al., 2012) 0, 50, 100 and 200 μM of Uranyl Acetate

Long/ Easy

High accuracy

Mitochondrial Antioxidant Content Assay

Measuring GSH content

(Shaki et al., 2012)
“GSH content was determined using DTNB as the indicator and spectrophotometer method for the isolated mitochondria. The mitochondrial fractions (0.5 mg protein/ml) were incubated with various concentrations of uranyl acetate for 1 h at 30 °C and then 0.1 ml of mitochondrial fractions was added into 0.1 mol/l of phosphate buffers and 0.04% DTNB in a total volume of 3.0 ml (pH 7.4). The developed yellow color was read at 412 nm on a spectrophotometer (UV-1601 PC, Shimadzu, Japan). GSH content was expressed as μg/mg protein.” (Shaki et al., 2012)

0, 50, 100, or 200 μM Uranyl Acetate


H2O2 Production Assay

Measuring H2O2 Production in isolated mitochondria

(Heyno et al., 2008)
“Effect of CdCl2 and antimycin A (AA) on H2O2 production in isolated mitochondria from potato. H2O2 production was measured as scopoletin oxidation. Mitochondria were incubated for 30 min in the measuring buffer (see the Materials and Methods) containing 0.5 mM succinate as an electron donor and 0.2 µM mesoxalonitrile 3‐chlorophenylhydrazone (CCCP) as an uncoupler, 10 U horseradish peroxidase and 5 µM scopoletin.” (Heyno et al., 2008)

0, 10, 30  μM Cd2+

2  μM antimycin A

Flow Cytometry ROS & Cell Viability

(Kruiderig et al., 1997)
For determination of ROS, samples taken at the indicated time points were directly transferred to FACScan tubes. Dih123 (10 mM, final concentration) was added and cells were incubated at 37°C in a humidified atmosphere (95% air/5% CO2) for 10 min. At t 5 9, propidium iodide (10 mM, final concentration) was added, and cells were analyzed by flow cytometry at 60 ml/min. Nonfluorescent Dih123 is cleaved by ROS to fluorescent R123 and detected by the FL1 detector as described above for Dc (Van de Water 1995)”  




Detection of hydrogen peroxide production

(Yuan et al., 2016)

Intracellular ROS production was measured using DCFH-DA as a probe. Hydrogen peroxide oxidizes DCFH to DCF. The probe is hydrolyzed intracellularly to DCFH carboxylate anion. No direct reaction with H2O2 to form fluorescent production.   

0-400 µM

Long/ Easy

High accuracy

H2-DCF-DA Assay

Detection of superoxide production

(Thiebault et al., 2007)

This dye is a stable nonpolar compound which diffuses readily into the cells and yields H2-DCF. Intracellular OH or ONOO- react with H2-DCF when cells contain peroxides, to form the highly fluorescent compound DCF, which effluxes the cell. Fluorescence intensity of DCF is measured using a fluorescence spectrophotometer. 0–600 µM

Long/ Easy

High accuracy

CM-H2DCFDA Assay **Come back and explain the flow cytometry determination of oxidative stress from Pan et al. (2009)**    

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Oxidative stress can happen in all forms of life.


List of the literature that was cited for this KE description. More help

Adam-Vizi, V., & Starkov, A. A. (2010). Calcium and mitochondrial reactive oxygen species generation: How to read the facts. Journal of Alzheimer's Disease : JAD, 20 Suppl 2, S413-S426. doi:10.3233/JAD-2010-100465

Al Dera, H. S. (2016). Protective effect of resveratrol against aluminum chloride induced nephrotoxicity in rats. Saudi Med J, 37(4), 369-378. doi:10.15537/smj.2016.4.13611

Andjelkovic, M., Djordjevic, A. B., Antonijevic, E., Antonijevic, B., Stanic, M., Kotur-Stevuljevic, J., . . . Bulat, Z. (2019). Toxic effect of acute cadmium and lead exposure in rat blood, liver, and kidney. International Journal of Environmental Research and Public Health, 16, 247. doi:10.3390/ijerph16020274

Barbier, O., Jcquillet, G., Tauc, M., Cougnon, M., & Poujeol, P. (2005). Effect of heavy metals on, and handling by, the  kidney. Nephron Physiology, 99, 105-110. doi:10.1159/000083981

Belyaeva, E. A., Sokolova, T. V., Emelyanova, L. V., & Zakharova, I. O. (2012). Mitochondrial electron transport chain in heavy metal-induced neurotoxicity : Effects of cadmium , mercury , and copper. Thescientificworld, 2012, 1-14. doi:10.1100/2012/136063

Bhadauria, S., & Flora, S. J. S. (2007). Response of arsenic-induced oxidative stress, DNA damage, and metal imbalance to combined administration of DMSA and monoisoamyl-DMSA during chronic arsenic poisoning in rats. Cell Biol Toxicol, 23, 91-104. doi:10.1007/s10565-006-0135-8

Blajszczak, C., & Bonini, M. G. (2017). Mitochondria targeting by environmental stressors : Implications for redox cellular signaling. Toxicology, 391, 84-89. doi:10.1016/j.tox.2017.07.013

Buelna-Chontal, M., Franco, M., Hernandez-Esquivel, L., Pavon, N., Rodriguez-Zalvala, J. S., Correa, F., . . . Chavez, E. (2017). CDP-choline circumvents mercury-induced mitochondrial damage and renal dysfunction. Cell Biology International, 41, 1356-1366. doi:10.1002/cbin.10871

Chtourou, Y., Garoui, E. m., Boudawara, T., & Zeghal, N. (2014). Protective role of silymarin against manganese-induced nephrotoxicity and oxidative stress in rat. Environ Toxicol, 29, 1147-1154. doi:10.1002/tox.21845

Ferreira, G. K., Cardoso, E., Vuolo, F. S., Michels, M., Zanoni, E. T., Carvalho-Silva, M., . . . Paula, M. M. S. (2015). Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats. Biochem. Cell Biol., 93, 548-557. doi:10.1139/bcb-2015-0030

Görlach, A., Bertram, K., Hudecova, S., & Krizanova, O. (2015). Calcium and ROS: A mutual interplay. Redox Biology, 6, 260-271. doi:doi:10.1016/j.redox.2015.08.010

Hancock, J. T., Desikan, R., & Neill, S. J. (2001). Role of reactive oxygen species in cell signalling pathways. Biochemical Society Transactions, 29(Pt 2), 345-350. doi:10.1042/0300-5127:0290345 [doi]

Hao, Y., Huang, J., Liu, C., Li, H., Liu, J., Zeng, Y., . . . Li, R. (2016). Differential protein expression in metallothionein protection from depleted uranium-induced nephrotoxicity. Scientific Reports, doi:10.1038/srep38942

Heyno, E., Klose, C., & Krieger-Liszkay, A. (2008). Origin of cadmium-induced reactive oxygen species production: Mitochondrial electron transfer versus plasma membrane NADPH oxidase. New Phytologist, 179, 687-699. doi:10.1111/j.1469-8137.2008.02512.x

Huerta-García, E., Perez-Arizti, J. A., Marquez-Ramirez, S. G., Delgado-Buenrostro, N. L., Chirino, Y. I., Iglesias, G. G., & Lopez-Marure, R. (2014). Titanium dioxide nanoparticles induce strong oxidative stress and mitochondrial damage in glial cells. Free Radical Biology and Medicine, 73, 84-94. doi:10.1016/j.freeradbiomed.2014.04.026

Jozefczak, M., Bohler, S., Schat, H., Horemans, N., Guisez, Y., Remans, T., . . . Cuypers, A. (2015). Both the concentration and redox state of glutathione and ascorbate influence the sensitivity of arabidopsis to cadmium. Annals of Botany, 116(4), 601-612. doi:10.1093/aob/mcv075

Kehrer, J. P. (2000). The Haber–Weiss reaction and mechanisms of toxicity. Toxicology, 149(1), 43-50. doi:

Kharroubi, W., Dhibi, M., Mekni, M., Haouas, Z., Chreif, I., Neffati, F., . . . Sakly, R. (2014). Sodium arsenate induce changes in fatty acids profiles and oxidative damage in kidney of rats. Environ Sci Pollut Res, 21, 12040-12049. doi:10.1007/s11356-014-3142-y

Kowaltowski, A. J., & Vercesi, A. E. (1999). Mitochondrial damage induced by conditions of oxidative stress. Free Radical Biology and Medicine, 26(3), 463-471. doi:

Kruidering, M., Van De Water, B., De Heer, E., Mulder, G. J., & Nagelkerke, J. F. (1997). Cisplatin-induced nephrotoxicity in porcine proximal tubular cells: Mitochondrial dysfunction by inhibition of complexes I to IV of the respiratory chain. The Journal of Pharmacology and Experimental Therapeutics, 280(2), 638-649.

Li, N., Ragheb, K., Lawler, G., Sturgis, J., Melendez, J. A., & Robinson, J. P. (2003). Mitochondrial complex I inhibitor rotenone induced apoptosis through enhancing mitochondrial reactive oxygen species production. The Journal of Biological Chemistry, 278(10), 8516-8525.

Liang, Shih-Shin & Shiue, Yow-Ling & Kuo, Chao Jen & Guo, Su-Er & Liao, Wei-Ting & Tsai, Eing. (2013). Online Monitoring Oxidative Products and Metabolites of Nicotine by Free Radicals Generation with Fenton Reaction in Tandem Mass Spectrometry. TheScientificWorldJournal. 2013. 189162. 10.1155/2013/189162.

Liu, S., Xu, L., Zhang, T., Ren, G., & Yang, Z. (2010). Oxidative stress and apoptosis induced by nanosized titanium dioxide in PC12 cells. Toxicology, 267, 172-177. doi:10.1016/j.tox.2009.11.012

Lunyera, J., & Smith, S. R. (2017). Heavy metal nephropathy: Considerations for exposure analysis. Kidney International, 92, 548-550. doi:

Miyayama, T., Arai, Y., Suzuki, N., & Hirano, S. (2013). Mitochondrial electron transport is inhibited by disappearance of metallothionein in human bronchial epithelial cells follwoing exposure to silver nitrate. Toxicology, 305, 20-29. doi:10.1016/j.tox.2013.01.004

Pan, Y., Leifer, A., Ruau, D., Neuss, S., Bonrnemann, J., Schmid, G., . . . Jahnen-Dechent, W. (2009). Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. Small, 5(8), 2067-2076. doi:10.1002/smll.200900466

Panday, A., Sahoo, M., Osorio, D., Barta, S. (2014). NADPH oxidases: an overview from structure to innate immunity-associated pathologies. Cell Mol Immunol 12, 5–23 (2015).

Pourahmad, J., Ghashang, M., Ettehadi, H. A., & Ghalandari, R. (2006). A search for cellular and molecular mechanisms involved in depleted uranium (DU) toxicity. Environmental Toxicology, 21(4), 349-354. doi:10.1002/tox.20196

Sabath, E., & Robles-Osorio, M. L. (2012). Renal health and the environment: Heavy metal nephrotoxicity. Revista Nefrologia, doi:10.3265/Nefrologia.pre2012.Jan.10928

Santos, N. A. G., Catão, C. S., Martins, N. M., Curti, C., Bianchi, M. L. P., & Santos, A. C. (2007). Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Archives of Toxicology, 81(7), 495-504. doi:10.1007/s00204-006-0173-2

Shaki, F., Hosseini, M. J., Ghazi-Khansari, M., & Pourahmad, J. (2012). Toxicity of depleted uranium on isolated rat kidney mitochondria. Biochimica Et Biophysica Acta - General Subjects, 1820(12), 1940-1950. doi:10.1016/j.bbagen.2012.08.015

Shaki, F., Hosseini, M., Ghazi-Khansari, M., & Pourahmad, J. (2013). Depleted uranium induces disruption of energy homeostasis and oxidative stress in isolated rat brain mitochondria. Metallomics, 5(6), 736-744. doi:10.1039/c3mt00019b

Sies, H. (Ed.), Oxidative Stress, Oxidants and Antioxidants, Academic Press, San Diego, CA (1991), pp. XV-XXII

Small, D. M., Sanchez, W. Y., Roy, S. F., Morais, C., Brooks, H. L., Coombes, J. S., . . . Gobe, G. (2018). N-acetyl-cysteine increases cellular dysfunction in progressive chronic kidney damage after acute kidney injury by dampening endogenous antioxidant responses. American Physiological Society - Renal Physiology, 314, F956-F968. doi:10.1152/ajprenal.00057.2017

Thiébault, C., Carrière, M., Milgram, S., Simon, A., Avoscan, L., & Gouget, B. (2007). Uranium induces apoptosis and is genotoxic to normal rat kidney (NRK-52E) proximal cells. Toxicological Sciences : An Official Journal of the Society of Toxicology, 98(2), 479-487. doi:kfm130 [pii]

Turk, E., Kandemir, F. M., Yildirim, S., Caglayan, C., Kucukler, S., & Kuzu, M. (2019). Protective effect of hesperidin on sodium arsenite-induced nephrotoxicity and hepatotoxicity in rats. Biological Trace Element Research, 189, 95-108. doi:10.1007/s12011-018-1443-6

Turrens, J. F. (2003). Mitochondrial formation of reactive oxygen species. The Journal of Physiology, 552(Pt 2), 335-344. doi:jphysiol.2003.049478 [pii]

Tyagi, R., Rana, P., Gupta, M., Khan, A. R., Bhatnagar, D., Bhalla, P. J. S., . . . Kushu, S. (2011). Differntial biochemical response of rat kidney towards low and high doses of NiCl2 as revealed by NMR spectroscopy. Journal of Applied Toxicology, 33, 134-141. doi:10.1002/jat.1730

Valko, M., Morris, H., & Cronin, M. T. (2005). Metals, toxicity and oxidative stress. Current Medicinal Chemistry, 12(10), 1161-1208. doi:10.2174/0929867053764635 [doi]

Wang, L., Li, J., Li, J., & Liu, Z. (2009). Effects of lead and/or cadmium on the oxidative damage of rat kidney cortex mitochondria. Biol.Trace Elem.Res., 137, 69-78. doi:10.1007/s12011-009-8560-1

Xu, X. M., & Moller, G. S. (2010). ROS removal by DJ-1. Plant Signaling & Behaviour, 5(8), 1034-1036. doi:10.4161/psb.5.8.12298

Yeh, Y., Lee, Y., Hsieh, Y., & Hwang, D. (2011). Dietary taurine reduces zinc-induced toxicity in male wistar rats. Journal of Food Science, 76(4), 90-98. doi:10.1111/j.1750-3841.2011.02110.x

Yuan, Y., Zheng, J., Zhao, T., Tang, X., & Hu, N. (2016). Uranium-induced rat kidney cell cytotoxicity is mediated by decreased endogenous hydrogen sulfide (H2S) generation involved in reduced Nrf2 levels. Toxicology Research, 5(2), 660-673. doi:10.1039/C5TX00432B

Zhao, R., Jiang, S., Zhang, L., & Yu, Z. (2019). Mitochondrial electron transport chain, ROS generation and uncoupling (review). International Journal of Molecular Medicine, 44(1), 3-15. doi:10.3892/ijmm.2019.4188