Changes of the mRNA Expression Pattern of Zn Transporters: a Probable Mechanism for Cadmium Retention and Zinc Redistribution in the Suckling Rat Tissues

Abstract

The present study was conducted to provide potential mechanism that may be responsible for Cd retention and Cd-induced Zn redistribution in tissues of suckling rat. For this purpose, suckling rats from mother receiving either tap water, Cd, or Cd + Zn during lactation period were sacrificed on postnatal day (PND) 14 and PND 21 for performing chemical and molecular analysis. Our results show that Cd exposure, although it does not affect the milk consumption, it clearly alters the lactational transfer, absorption, and distribution of Zn in the suckling rat organism. At the molecular level, Cd caused upregulation of ZIP 3, ZIP 4, and ZIP 8 gene expressions in the mammary gland of mothers rats and in the intestine of their pups but decreased the expression of ZnT 2 and ZnT 4 only in the mammary tissue at PND 14 and PND 21. Zn supply reversed the Cd-induced decrease in the neonatal Zn apparent absorption and restores the gastrointestinal, brain, and plasma levels of this essential element in the suckling rat organism at PND 14 and PND 21. Also, with this treatment, the gene expressions of ZnT 1 in the mammary gland and ZnT 4 in the neonatal intestine were found to be upregulated at PND 21. Furthermore, our results show that Cd or Cd + Zn treatment increase the neonatal hepatic MTs accumulation at PND 14 only. These results imply that the downregulation of ZnT as well as the overexpression of ZIP transporters, in responses to the Zn depletion induced by Cd in the tissues of lactating rat and their offspring, play a major role in Cd accumulation and Zn redistribution in tissues of suckling rat.

Protective role of zinc against the toxicity induced by exposure to cadmium during gestation and lactation on testis development

“…In fact, during the lactation period, Cd is thought to be transported from maternal plasma to mammary gland and secreted into breast milk as well as essential element like Zn. Our previous study [15] imply that the downregulation of ZnT as well as the overexpression of ZIP transporters in the mammary gland of lactating rat and in the intestine of their offspring, play a major role in Cd accumulation and Zn redistribution in tissues of suckling rats. Zn testicular depletion during lactation seems also to be due to its sequestration by Cd-induced hepatic metallothioneins (MTs) from the plasma in the organism of offspring rats, thereby increasing its concentration in the liver and kidneys and probably restricting Zn supply to other tissues [18].…”

“…The protective effect of Zn against Cd-induced testicular damage may be due to interaction between the two metals at three major sites: small intestine, liver and testis. In the small intestine, enhanced consumption of Zn may decrease Cd absorption from the digestive tract and its accumulation in the offspring rat's organism, and as a result, it may protect against the toxic effects of Cd [15]. In the liver, interaction between Cd and Zn to induce MTs which sequesters Cd had been suggested as the most likely mechanisms [18].…”

Inhibitory effect of cadmium on estrogen signaling in zebrafish brain and protection by zinc

“…Furthermore, quantification of the GFP expression in the tg‐(cyp19a1b‐GFP) zebrafish in multiple field of view mode was performed as previously reported (Brion et al , ) and confirmed the protective effect of Zn (data not shown). Although Zn concentrations were not measured in fish and culture cells used in this study, it is possible that the protection provided by this oligoelement against Cd‐induced toxicity might result from an increase of Zn availability due to Zn supplementation as reported by some authors (Chemek et al , ; Chouchene et al , ). The correction observed at the zfERs transactivation level leads to think that the Zn finger motifs could be involved at first in Cd toxicity and later in Zn protection.…”

Effects of cadmium on intracellular cation homoeostasis in the yeastSaccharomyces cerevisiae

“…Among them, cadmium is one of the most toxic metals classified by International Agency for Research on Cancer as a human carcinogen. It has no biological function (Jones and Gadd 1990;Chemek et al 2015) and can exert toxic effects at low concentrations, including inhibition of growth (Rani et al 2013) and cell death (Kim et al 2013). It is considered genotoxic and carcinogenic for lung, kidney, and prostate (Navarro Silvera and Rohan 2007;Stone 2008).…”