Zinc Chloride Can Mitigate the Alterations in Metallothionein and Some Apoptotic Proteins Induced by Cadmium Chloride in Mice Hepatocytes: A Histological and Immunohistochemical Study

Abstract

The heavy metal cadmium is extremely harmful to both humans and animals. Zinc supplementation protects the biological system and reduces cadmium-induced toxicity. This study aimed to determine whether zinc chloride (ZnCl2) could protect male mice with the damaged liver induced by cadmium chloride (CdCl2). The protective role of zinc chloride and expression of the metallothionein (MT), Ki-67, and Bcl-2 apoptotic proteins in hepatocytes were studied after subchronic exposure of mice to cadmium chloride for 21 days. Thirty male mice were randomly categorized into 6 groups (5 mice/group) as follows: a control group that did not receive any treatment, a group given ZnCl2 at 10 mg/kg alone, and two groups received ZnCl2 (10 mg/kg) in combination with CdCl2 at two concentrations (1.5 and 3 mg/kg), while the last two groups received CdCl2 alone at 1.5 and 3 mg/kg, respectively. Immunohistochemical examination revealed a decrease in Ki-67 expression in Kupffer and endothelial cells, which reflected cell proliferation downregulation accompanied by MT increased expression. However, the Bcl-2 was ameliorated and reduced to demonstrate an enhanced rate of necrosis rather than apoptosis. Furthermore, histopathological results showed significant alteration such as hepatocytes with a pyknotic nucleus, infiltration of inflammatory cells around the central vein, and the presence of many binucleated hepatocytes. Zinc chloride treatment resulted in histological and morphological improvements that were average in the expression of apoptosis proteins modifications induced by cadmium. Our findings revealed that the positive effects of zinc might be linked to the high metallothionein expression and enhanced cell proliferation. Furthermore, at low-dose exposure, cadmium-induced damage to cells could be more closely related to necrosis rather than apoptosis.