Diphenyl diselenide potentiates nephrotoxicity induced by mercuric chloride in mice Ricardo Brandão, a * Rafael N. Moresco, a Luziane P. Bellé, a Marlon R. Leite, b Mayara L. de Freitas, b Adalto Bianchini c and Cristina W. Nogueira b ABSTRACT: Following our long‐standing interest in the mechanisms involved in selenium toxicity, the aim of this work was to extend our previous studies to gain a better understanding of mercuric chloride (HgCl 2 ) + diphenyl diselenide (PhSe) 2 toxicity. Mice received one daily dose of HgCl 2 (4.6 mg kg -1 , subcutaneously) for three consecutive days. Thirty minutes after the last injection of HgCl 2 , mice received a single dose of (PhSe) 2 (31.2 mg kg -1 , subcutaneously). Five hours after (PhSe) 2 administration, mice were euthanized and δ‐aminolevulinate dehydratase, catalase (CAT), glutathione S‐transferase (GST) and Na + ,K + ‐ATPase activities as well as thiobarbituric acid‐reactive substances (TBARS), ascorbic acid and mercury levels were determined in kidney and liver. Parameters in plasma (urea, creatinine, protein and erythropoietin), whole blood (hematocrit and hemoglobin) and urine (protein) were also investigated. HgCl 2 + (PhSe) 2 exposure caused a decrease in renal GST and Na + ,K + ‐ATPase activities and an increase in renal ascorbic acid and TBARS concentrations when compared with the HgCl 2 group. (PhSe) 2 potentiated the increase in plasma urea caused by HgCl 2 . HgCl 2 + (PhSe) 2 exposure caused a reduction in plasma protein levels and an increase in hemoglobin and hematocrit contents when compared with the HgCl 2 group. There was a significant reduction in hepatic CAT activity and an increase in TBARS levels in mice exposed to HgCl 2 + (PhSe) 2 when compared with the HgCl 2 group. The results demonstrated that (PhSe) 2 did not modify mercury levels in mice. In conclusion, (PhSe) 2 potentiated damage caused by HgCl 2 affecting mainly the renal tissue. Copyright © 2011 John Wiley & Sons, Ltd. Keywords: kidney; liver; mercury; selenium; toxicity INTRODUCTION The industrial use of mercury and its general toxic effects on human and animal systems are well known (Rao, 1997). In fact, mercury promotes the formation of reactive oxygen species (ROS) such as hydrogen peroxides (Hussain et al., 1999). Accordingly, mercury exposure has been demonstrated to induce lipid peroxidation detected by increased thiobarbituric acid‐reactive substances (TBARS) in liver, kidney, brain and other tissues (Huang et al., 1996). Moreover, mercury exposure can cause inhibition of sulfhydryl enzymes such as δ‐aminolevuli- nate dehydratase (δ‐ALA‐D; Emanuelli et al., 1996) and Na + , K + ‐ATPase (Anner and Moosmayer, 1992). Selenium compounds are considered ‘ Janus compounds’ , i.e. products with a double face, because of their contrasting behavior that is dose‐dependent. At low doses, organoselenium has beneficial effects, whereas high doses are toxic. The threshold dose for these opposing properties has not yet been established (Nogueira and Rocha, 2010). Selenium is a structural component of several enzymes with physiological antioxidant properties, including glutathione peroxidase and thioredoxin reductase (Rotruck et al., 1973; Xia et al., 2002). Consistent with the ‘double face’ property of selenium compounds, toxicological properties of (PhSe) 2 have been reported (Nogueira et al., 2004). In fact, (PhSe) 2 inhibits δ‐ALA‐D activity in human blood (Nogueira et al., 2003a) and cerebral Na + ,K + ‐ATPase activity (Borges et al., 2005) by interacting with SH groups of these enzymes. Diphenyl diselenide, (PhSe) 2 , a synthetic organoselenium compound, has been reported in view of its pharmacological properties such as anti‐inflammatory, antinociceptive, anti‐ulcer, neuroprotective and antioxidant in different experimental models (Nogueira et al., 2004; Borges et al., 2006; Barbosa et al., 2006; Savegnago et al., 2006, 2007). It is important to point out that (PhSe) 2 is not a natural compound found in the environment, but a synthetic organoselenium molecule (Paulmier, 1986). The interaction between mercury and selenium in the body of mammals has been known for more than three decades. Since Parizek and Ostadalova (1967) found that the toxicity of inorganic mercury was decreased by simultaneous injection of selenite, many studies have been carried out to examine the role of selenium in the detoxification of mercury, which have led to many hypotheses about the mechanism of this interaction (Cuvin‐Aralar and Furness, 1991). Regarding the interaction between organic selenium and mercury, data have been reported on protective (Farina et al. 2003a; De Freitas et al., 2009) and pro‐oxidative effects (Farina et al., 2004). *Correspondence to: R. Brandão, Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, CEP 97105‐900, Santa Maria, RS, Brazil. E-mail: ricardo_br79@yahoo.com.br a Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, CEP 97105‐900, Santa Maria, RS, Brazil b Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105‐900, Santa Maria, RS, Brazil c Departamento de Ciências Fisiológicas, Universidade Federal do Rio Grande‐ FURG, CEP 96201‐900, Rio Grande, RS, Brazil J. Appl. Toxicol. 2010; 31: 773–782 Copyright © 2011 John Wiley & Sons, Ltd. Research Article Received: 19 July 2010, Revised: 27 October 2010, Accepted: 27 October 2010 Published online in Wiley Online Library: 24 January 2011 (wileyonlinelibrary.com) DOI 10.1002/jat.1631 773