Environmental Toxicology and Pharmacology 28 (2009) 225–231 Contents lists available at ScienceDirect Environmental Toxicology and Pharmacology journal homepage: www.elsevier.com/locate/etap Lungs: Remote inflammatory target of systemic cadmium administration in rats Milena Kataranovski a,b,∗ , Ivana Mirkov a , Sandra Belij a , Miroslav Nikolic c , Lidija Zolotarevski d , Danica Ciric a , Dragan Kataranovski a,e a Department of Ecology, Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, 11000 Belgrade, Serbia b Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia c Institute for Multidisciplinary Research, University of Belgrade, 11030 Belgrade, Serbia d Institute for Pathology, Military Medical Academy, 11000 Belgrade, Serbia e Institute of Zoology, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia article info Article history: Received 17 February 2009 Received in revised form 13 April 2009 Accepted 14 April 2009 Available online 21 April 2009 Keywords: Rats Intraperitoneal cadmium Lung inflammation abstract Pulmonary inflammation is a biological response to cadmium entering the body via the respiratory route. Systemic administration of this metal revealed the lungs as a significant site of its disposition. In this study, the presence of basic indicators of lung inflammation (leukocyte infiltration and activity of cells recovered from lungs by enzyme digestion) was analyzed in the rat model of acute systemic cadmium intoxication. Intraperitoneal administration of both cadmium doses (0.5 mg/kg and 1.0 mg/kg) resulted in increased numbers of neutrophils. Signs of spontaneous activation of lung cells including the capacity of reduction of nitroblue tetrazolium (NBT), increase in myeloperoxidase (MPO) intracellular content and increase in interleukin-6 (IL-6) production were noted at both cadmium doses. Increased lung cell responsiveness to stimulation in vitro was noted at the higher cadmium dose. The presence of pulmonary inflamma- tory parameters in rats administered intraperitoneally with cadmium revealed the lungs as remote inflammatory targets of this metal. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Cadmium is one of the most toxic metals in the environment. Its toxicity as an industrial pollutant, a food contaminant and one of the main components in cigarette smoke is well documented (Morselt, 1991). Cadmium adversely affects a number of organs and tissues including the kidneys, liver, lungs, testis, brain, bone, and blood (WHO, 1992; U.S. Department of Health and Human Services, 1997). The liver and kidneys are two primary organs in which the systemic toxicity of this metal is expressed (Kayama et al., 1995a,b). Exposure to particulate cadmium and cadmium fumes or experimental intratracheal instillation of cadmium results in pul- monary (proximal) toxicity (Driscoll et al., 1992; Oberdorster, 1992). Perfused or orally administered cadmium caused tissue damage in the gastrointestinal tract (Valberg et al., 1977; Andersen et al., 1988). Studies of both proximal (pulmonary) and distal toxicity (to liver and kidneys) in respective target tissues/organs demonstrated oxidative stress and inflammation as the underlying mechanisms ∗ Corresponding author at: Department of Ecology, Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Despota Stefana 142, Belgrade, Serbia. Tel.: +381 11 2078375; fax: +381 11 2761433. E-mail address: milena@ibiss.bg.ac.rs (M. Kataranovski). (Gavett and Oberdorster, 1994; Kayama et al., 1995a,b; Rikans and Yamano, 2000). Tissue infiltration with leukocytes and their local proinflammatory effects are considered responsible for pulmonary toxicity following intratracheal instillation of cadmium (Driscoll et al., 1992). Production of reactive oxygen species and inflammation- relevant cytokines by leukocytes infiltrating liver and kidney tissue (Kayama et al., 1995a,b) and by resident tissue cells (Dong et al., 1998; Souza et al., 2004) is believed to participate in liver damage following systemic cadmium administration. Toxicity of cadmium to liver and kidneys is the most fre- quently studied aspect of distal toxicity of this metal. Studies of intraperitoneal cadmium administration in rats (Manca et al., 1991) demonstrated oxidative stress responses in other organs beside liver, including lungs and brain, suggesting these organs as remote targets of systemic cadmium toxicity. Our previous study in rats administered intraperitoneally with cadmium, showed hepatotoxicity and nephrotoxicity judging on increased serum levels of alanine aminotransferase (AST) and changes in osmolarity and creatinine clearance (Kataranovski et al., 1998). By using this rat model of acute systemic cadmium administration, toxicity to lungs of this metal was examined in this study. Cellular (lung cell infiltration and activity) and biochem- ical (lung malondialdehyde content) indicators of inflammation were evaluated as an index of pulmonary toxicity in rats following cadmium administration. Evidence was obtained to demonstrate 1382-6689/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.etap.2009.04.008