Interference with zinc homeostasis and oxidative stress induction as probable mechanisms for cadmium-induced embryo-toxicity in zebrafish.

The present study was conducted to provide new insights into the mechanisms that may be responsible for cadmium (Cd)-induced toxicity in zebrafish larvae as well as the role of the trace element zinc (Zn) in reversing Cd harmful effects. For this purpose, zebrafish eggs were exposed to Cd or/and Zn for 96 h. The effects on morphological aspect; mortality rate; Cd, Zn, and metallothionein (MT) levels; oxidative stress biomarkers; as well as molecular expression of some genes involved in Zn metabolism (Zn-MT, ZIP10, and ZnT1) and in antioxidant defense system (Cu/Zn-SOD, CAT and GPx) were examined. Our results showed that Cd toxicity was exerted, initially, by an interference with Zn metabolism. Thus, Cd was able to modify the expression of the corresponding genes so as to ensure its intracellular accumulation at the expense of Zn, causing its depletion. An oxidative stress was then generated, representing the second mode of Cd action which resulted in developmental anomalies and subsequently mortality. Interestingly, significant corrections have been noted following Zn supplementation based, essentially, on its ability to interact with the toxic metal. The increases of Zn bioavailability, the improvement of the oxidative status, as well as changes in Zn transporter expression profile are part of the protection mechanisms. The decrease of Cd-induced MTs after Zn supplement, both at the protein and the mRNA level, suggests that the protection provided by Zn is ensured through mechanisms not involving MT expression but which rather depend on the oxidative status.