Environmental Toxicology and Pharmacology 48 (2016) 272–277 Contents lists available at ScienceDirect Environmental Toxicology and Pharmacology j o ur nal ho me page: www.elsevier.com/lo cate/etap Lead accumulation and metallothionein content in female rats of different ages and generations after daily intake of Pb-contaminated food Cássia Regina Bruno Nascimento, Wagner Ezequiel Risso, Claudia Bueno dos Reis Martinez ∗ Department of Physiological Sciences, State University of Londrina, Postal Box 10011, Londrina, PR 86057-970, Brazil a r t i c l e i n f o Article history: Received 1 June 2016 Received in revised form 30 October 2016 Accepted 1 November 2016 Available online 3 November 2016 Keywords: Feed exposure Maternal milk Metal ingestion Offspring Organs accumulation Prenatal exposure a b s t r a c t Female Wistar rats of different ages (45, 90 and 140 days) and generations (mothers and offspring) were fed a feed containing 2.0 mg of Pb kg -1 daily from weaning and the Pb accumulation was determined in different organs and in maternal milk, in addition metallothioneins (MTs) content was determined in the liver and kidneys. The results showed that Pb accumulation exhibited the following pattern: bone > liver > kidney > gut > blood cells > muscle > brain > ovary. Bones accumulated the most Pb in all ani- mals, with its concentration increasing with age and prenatal exposure. Pb accumulation in the liver, kidney and blood cells, did not follow a consistent pattern with increasing age and our data did not indi- cate a relationship between the presence of MTs in liver and kidney and metal accumulation in these organs. However, in the offspring and with increasing age, Pb accumulated in more organs. Mothers fed with Pb produced contaminated milk, exposing their offspring to the metal via nursing Thus, increasing age and prenatal exposure increases susceptibility to Pb toxicity-induced damage. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Lead (Pb) poisoning remains a major public health hazard, par- ticularly in developing countries, by causing various deleterious effects on renal, hematopoietic, and reproductive functions as well as on the central nervous system (Flora et al., 2012; Beier et al., 2015). Pb is a metal that, mostly through anthropogenic action, can be found in soil, water, and the atmosphere; humans can be exposed via ingestion of contaminated water or food sources, among other routes. Nevertheless, the dietary intake of Pb is the main source of human exposure to this metal (EFSA, 2012). Lead is one of the most studied metal elements, and its accumu- lation in organisms may cause harmful effects over time (Flora et al., 2012). Lead is absorbed into the bloodstream via the gastrointesti- nal tract and can be deposited in organs such as the liver, kidneys, lungs, brain, spleen, heart, muscles and bones; approximately 94% and 73% of the total Pb in the body is found in the bones in adults and children, respectively (ATSDR, 2007). Younger organisms tend to accumulate higher amounts of lead compared with adults, as ∗ Corresponding author. E-mail addresses: cbueno@uel.br, claudiabrmartinez@gmail.com (C.B.d.R. Martinez). their mucous membranes are more permeable and their defenses are not fully effective (Winiarska-Mieczan and Kwiecie ´ n, 2016). Lead accumulated in bones may be gradually released into the bloodstream even after exposure has ceased, particularly during physiologic or pathologic bone demineralization periods, such as pregnancy, lactation and osteoporosis (EFSA, 2012). Thus, prena- tal exposure to Pb may harm maternal health and fetal and infant development even if maternal exposure levels are low. Further- more, as bones constitute the main Pb reservoir over decades, women and their offspring may be at risk of continuous exposure well after exposure has ceased (CDC, 2010). Metallothioneins (MTs) are low-molecular-weight intracellular proteins that are rich in cysteine residues and have high affinity for essential and non-essential metals (Park et al., 2001). These pro- teins contribute to the homeostasis of some essential metals and act as a protective mechanism against metal toxicity (Klaassen et al., 1999). Although some studies have linked MTs to Pb detoxifica- tion, information on Pb-driven MTs induction mechanisms remains scarce (Dai et al., 2013). Thus, the aim of the present study was to evaluate how age and maternal transfer influence lead accumulation in different organs. Furthermore, MTs content in kidney and liver Pb was also assessed. To accomplish these objectives, female Wistar rats of different ages http://dx.doi.org/10.1016/j.etap.2016.11.001 1382-6689/© 2016 Elsevier B.V. All rights reserved.