Recently, Valko et al. (2015) from Bratislava contributed a comprehensive review on the role of redox and non-redox metals in human disease. A typical feature of some metals, such as copper and iron, is that at low concentrations they are essential for health; whereas, at higher concentrations they can be toxic (Finazzi and Arosio 2014; Dusek et al. 2015; Gaetke et al. 2014). For example, superoxide radical anions formation followed by the generation of hydroxyl radicals has been reported for both copper and iron at high concentrations (Valko et al. 2015). A further mechanism that contributes to the toxicity of some metals involves their ability to compete with other metals that have essential functions in mammalian cells. Cadmium, for instance, acts as a substitute for copper and zinc, thus describing a key molecular mechanism of cadmium-induced hepatotoxicity (Valko et al. 2015). Finally, the interference of iron and manganese by lead causes a disruption in oxygen and energy consumption during the fetal stage in humans (Kopp et al. 2012). The current review article of Valko and colleagues systematically discusses the biochemistry of metal-induced radicals derived from oxygen and nitrogen and finally focusses on the toxic mechanisms of iron, copper, arsenic, cadmium, and zinc, as well as their role in human disease.
Control mechanisms underlying oxidative stress still remain a topic at the forefront of toxicological research, such as the decoding of different signaling pathways involved in oxidative damage (Toledo et al. 2014; Brobey et al. 2015; Liu et al. 2005; Marashi et al. 2008) or antioxidant defense mechanisms (Lim et al. 2014; Tangkosakul et al. 2009). In particular, research on oxidative stress induced by nanosized materials has become more and more important in recent years (Møller et al. 2014; Zhang et al. 2015; Bondarenko et al. 2013). Moreover, the relatively high exposure of humans to some heavy metals (Hengstler et al. 2003; King et al. 2015; Jaishankar et al. 2014; Tom and Fletcher 2014; Shiue and Hristova 2014; Pizzino et al. 2014; Jung et al. 2003) has motivated intensive research on metal toxicity, including nickel-induced DNA damage (Yao and Costa 2014), manganese-induced neurotoxicity (Krishna et al. 2014; Kumasaka et al. 2014), and lead-associated mimicry of essential minerals and immunotoxicity (Breton et al. 2013; Jorissen et al. 2013). As a result, the review presented by Valko and colleagues is extremely relevant to scientists working in these fields of research.
References
Bondarenko O, Juganson K, Ivask A, Kasemets K, Mortimer M, Kahru A (2013) Toxicity of Ag, CuO and ZnO nanoparticles to selected environmentally relevant test organisms and mammalian cells in vitro: a critical review. Arch Toxicol 87(7):1181–1200. doi:10.1007/s00204-013-1079-4 (Review)
Breton J, Le Clère K, Daniel C, Sauty M, Nakab L, Chassat T, Dewulf J, Penet S, Carnoy C, Thomas P, Pot B, Nesslany F, Foligné B (2013) Chronic ingestion of cadmium and lead alters the bioavailability of essential and heavy metals, gene expression pathways and genotoxicity in mouse intestine. Arch Toxicol 87(10):1787–1795. doi:10.1007/s00204-013-1032-6
Brobey RK, Dheghani M, Foster PP, Kuro OM, Rosenblatt KP (2015) Klotho regulates 14-3-3ζ monomerization and binding to the ASK1 signaling complex in response to oxidative stress. PLoS ONE 10(10):e0141968. doi:10.1371/journal.pone.0141968 (eCollection)
Dusek P, Roos PM, Litwin T, Schneider SA, Flaten TP, Aaseth J (2015) The neurotoxicity of iron, copper and manganese in Parkinson’s and Wilson’s diseases. J Trace Elem Med Biol 31:193–203
Finazzi D, Arosio P (2014) Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration. Arch Toxicol 88(10):1787–1802. doi:10.1007/s00204-014-1329-0 (Review)
Gaetke LM, Chow-Johnson HS, Chow CK (2014) Copper: toxicological relevance and mechanisms. Arch Toxicol 88(11):1929–1938. doi:10.1007/s00204-014-1355-y (Review)
Hengstler JG, Bolm-Audorff U, Faldum A, Janssen K, Reifenrath M, Götte W, Jung D, Mayer-Popken O, Fuchs J, Gebhard S, Bienfait HG, Schlink K, Dietrich C, Faust D, Epe B, Oesch F (2003) Occupational exposure to heavy metals: DNA damage induction and DNA repair inhibition prove co-exposures to cadmium, cobalt and lead as more dangerous than hitherto expected. Carcinogenesis 24(1):63–73
Jaishankar M, Tseten T, Anbalagan N, Mathew BB, Beeregowda KN (2014) Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol 7(2):60–72. doi:10.2478/intox-2014-0009 (Review)
Jorissen A, Plum LM, Rink L, Haase H (2013) Impact of lead and mercuric ions on the interleukin-2-dependent proliferation and survival of T cells. Arch Toxicol 87(2):249–258. doi:10.1007/s00204-012-0926-z
Jung D, Bolm-Audorff U, Faldum A, Hengstler JG, Ismail Attia D, Janssen K, Reifenrath R, Bienfait HG, Mayer-Popken O, Konietzko J (2003) Immunotoxicity of co-exposures to heavy metals: in vitro studies and results from occupational exposure to cadmium, cobalt and lead. EXCLI J 2:31–44
King KE, Darrah TH, Money E, Meentemeyer R, Maguire RL, Nye MD, Michener L, Murtha AP, Jirtle R, Murphy SK, Mendez MA, Robarge W, Vengosh A, Hoyo C (2015) Geographic clustering of elevated blood heavy metal levels in pregnant women. BMC Public Health 15(1):1035. doi:10.1186/s12889-015-2379-9
Kopp RS, Kumbartski M, Harth V, Brüning T, Käfferlein HU (2012) Partition of metals in the maternal/fetal unit and lead-associated decreases of fetal iron and manganese: an observational biomonitoring approach. Arch Toxicol 86(10):1571–1581
Krishna S, Dodd CA, Hekmatyar SK, Filipov NM (2014) Brain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water. Arch Toxicol 88(1):47–64. doi:10.1007/s00204-013-1088-3
Kumasaka MY, Yajima I, Ohgami N, Naito H, Omata Y, Kato M et al (2014) Commentary to Krishnab et al. (2014): rain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water. Arch Toxicol 88(5):1185–1186. doi:10.1007/s00204-014-1221-y
Lim JL, Wilhelmus MM, de Vries HE, Drukarch B, Hoozemans JJ, van Horssen J (2014) Antioxidative defense mechanisms controlled by Nrf2: state-of-the-art and clinical perspectives in neurodegenerative diseases. Arch Toxicol 88(10):1773–1786. doi:10.1007/s00204-014-1338-z (Review)
Liu S, Deng G, Tu Z, Li J, Liu M, Xiao X (2005) The effects of αB-crystallin on mitochondrial death pathway during hydrogen peroxide induced apoptosis. EXCLI J 4:7–24
Marashi SA, Rezaei-Tavirani M, Zali H, Shokrgozar MA (2008) Mitochondrial DNA might be influenced in calprotectin-induced cell death. EXCLI J 7:163–168
Møller P, Christophersen DV, Jensen DM, Kermanizadeh A, Roursgaard M, Jacobsen NR, Hemmingsen JG, Danielsen PH, Cao Y, Jantzen K, Klingberg H, Hersoug LG, Loft S (2014) Role of oxidative stress in carbon nanotube-generated health effects. Arch Toxicol 88(11):1939–1964. doi:10.1007/s00204-014-1356-x (Review)
Pizzino G, Bitto A, Interdonato M, Galfo F, Irrera N, Mecchio A, Pallio G, Ramistella V, De Luca F, Minutoli L, Squadrito F (2014) Altavilla D (2014) Oxidative stress and DNA repair and detoxification gene expression in adolescents exposed to heavy metals living in the Milazzo-Valle del Mela area (Sicily, Italy). Redox Biol 2:686–693. doi:10.1016/j.redox.2014.05.003 (eCollection)
Shiue I, Hristova K (2014) Higher urinary heavy metal, phthalate and arsenic concentrations accounted for 3–19% of the population attributable risk for high blood pressure: US NHANES, 2009–2012. Hypertens Res 37(12):1075–1081. doi:10.1038/hr.2014.121
Tangkosakul T, Tantimongcolwat T, Isarankura-Na-Ayudhya C, Mejare M, Bülow L (2009) Prachayasittikul V (2009) Native and chimeric metal-binding lactate dehydrogenase as detection and protection tools for oxidative stress induced by Fenton’s reaction. EXCLI J 8:1–11
Toledo FD, Pérez LM, Basiglio CL, Ochoa JE, Sanchez Pozzi EJ, Roma MG (2014) The Ca2+-calmodulin-Ca2+/calmodulin-dependent protein kinase II signaling pathway is involved in oxidative stress-induced mitochondrial permeability transition and apoptosis in isolated rat hepatocytes. Arch Toxicol 88(9):1695–1709. doi:10.1007/s00204-014-1219-5
Tom M, Fletcher TD (2014) McCarthy DT (2014) Heavy metal contamination of vegetables irrigated by urban stormwater: a matter of time? PLoS ONE 9(11):e112441. doi:10.1371/journal.pone.0112441 (eCollection)
Valko M, Jomova K, Rhodes CJ, Kuča K, Musílek K (2015) Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Arch Toxicol. doi:10.1007/s00204-015-1579-5 (Review)
Yao Y, Costa M (2014) Toxicogenomic effect of nickel and beyond. Arch Toxicol 88(9):1645–1650. doi:10.1007/s00204-014-1313-8 (Review)
Zhang T, Wang Y, Kong L, Xue Y, Tang M (2015) Threshold dose of three types of quantum dots (QDs) induces oxidative stress triggers DNA damage and apoptosis in mouse fibroblast L929 cells. Int J Environ Res Public Health 12(10):13435–13454
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Marchan, R. Highlight report: redox—metals in toxicology. Arch Toxicol 89, 2475–2476 (2015). https://doi.org/10.1007/s00204-015-1647-x
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DOI: https://doi.org/10.1007/s00204-015-1647-x