Induction of Metallothionein in Rat Liver by Zinc Exposure: A Dose and Time Dependent Study

Abstract

Metallothioneins (MTs) are low molecular weight ubiquitous metalloproteins with high cysteine (thiol) content. The intracellular concentration of zinc (Zn) is tightly regulated and MT plays a crucial role in it. The present study investigates the relationship between the Zn status (as a function of Zn concentration and time) in the rat liver and the occurrence of hepatic MT. For dose dependent study, four experimental groups, one control and three receiving different levels of metal supplementation, were chosen [Group 1 control and Group 2, Group 3, Group 4 receiving subcutaneous dose of 10, 50 and 100 mg of Zn/kg body weight (in the form of ZnSO·7HO), respectively]. For the time dependent expression of MT, again four experimental groups, i.e. Group 5 control and Group 6, Group 7, Group 8 receiving 50 mg of Zn/kg body weight (in the form of ZnSO·7HO) subcutaneously and sacrificed at different time intervals after last injection i.e. 6, 18, 48 h, respectively were chosen. Isolation of MT was done by using combination of gel filtration and ion exchange chromatography while characterization of MT fraction was carried in the wavelength range 200-400 nm. Expression of MT was studied by using Western blot analysis. The results revealed that the MT expression increases with increasing the dose of Zn administered and maximum at 18 h after last Zn injection. Accumulation of MT with increase dose would help in maintaining the intracellular Zn concentration by its sequestration which further reduces the possibility of undesirable binding of Zn to other proteins significantly and maintains Zn homeostasis. The maximum expression of MT at 18 h is indicative of its half life.

Zinc alleviates the heat stress of primary cultured hepatocytes of broiler embryos via enhancing the antioxidant ability and attenuating the heat shock responses

“…In vivo, previous researches have indicated that dietary supplementation with Zn could increase MT mRNA expression in the liver of broilers ( Azad et al., 2017 ; Zhang et al., 2017 ; Zhu et al., 2017b ). In vitro, it has been reported that the induction of MT conferred protection against ROS in liver ( Garla et al., 2017 ), kidney ( Sharma et al., 2002 ) and islet ( Li et al., 2004 ) cells. In the present study, either iZn or oZn increased MT mRNA expression in heat-stressed hepatocytes, suggesting that Zn-treated hepatocytes might be better prepared to deal with oxidative stress induced by heat stress.…”

Chronic pancreatitis in farmed pigs fed excessive zinc oxide

“…Zn injection has induced metallothionein biosynthesis in the pancreas 17 and kidneys 19 of pigs and the livers of rats. 5 We did not investigate the expression of metallothionein in our case; however, high levels of induced metallothionein might have bound Zn in the tissues and blocked staining of the Zn.…”

Deadly excess copper

“…The oral administration of zinc leads to the expression of metallothioneins in the enterocytes, which bind the copper taken up with food and prevent its transfer into the bloodstream. During the process of natural turnover of enterocytes, bound copper is excreted with the feces [ [242] , [243] , [244] , [245] , [246] , [247] ]. In addition, zinc salts also induce the expression of metallothioneins in the liver and thus strengthen the endogenous defense [ 248 ].…”