Metallothionein and Heat Shock Protein Expression during Acute Liver Injury and Regeneration in Rats

Abstract

Metallothioneins (MT) are cytosolic proteins rich in cysteine which play a physiological role in metal ion homeostasis. Heat shock proteins (HSPs) are expressed in various organs in response to different stress stimuli. The purpose of the present study was to examine the intrahepatic distribution of MT and HSP-27, -70 and -90 in two different experimental models of acute liver injury and regeneration, induced by either thioacetamide, or carbon tetrachloride administration in male Wistar rats. Toxicological endpoints and markers of hepatocellular regeneration were assessed at various time points following toxin administration. The enzymatic activities of aspartate and alanine aminotransferases in serum, and histological findings in the liver were used to estimate toxin-induced injury. Tritiated thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index were used to estimate liver regeneration. MT and HSPs were detected immunohistochemically. At the time of maximum liver injury, moderate MT and intense HSPs expression was prominent in hepatocytes in the vicinity of necrotic areas. At the time of maximum hepatocellular proliferation, intense MT and HSP-90 staining was evident in all hepatocytes, while at the same time, mild HSP-27 and HSP-70 immunoreactivity was noted. Our findings indicate that the differential distribution of MT and HSPs in the liver after toxin-induced injury, in common with the observed pattern of staining, reflect liver proliferating capacity.

Zinc and the Liver: An Active Interaction

“…In Long-Evans Cinnamon (LEC) rats, characterized by an abnormal Cu deposition in the liver due to a lack of the Cu transporter P-type adenosine triphosphatase, Zn administration prevented acute hepatitis by increasing tissue MT concentrations, reducing Cu absorption, and interfering with Fe metabolism [67]. It is well documented that liver MT expression increases during acute liver injury [68,69]. It is believed that the induction of MT expression increases Zn levels in the injured hepatic parenchyma in order for the cells to compensate for the oxidative stress.…”

Protective role of melatonin in cyclosporine A-induced oxidative stress in rat liver

“…It is known that in response to different types of stress, such as oxidative stress, the cells rapidly produce a series of proteins, known as heat shock proteins (HSP), and other different proteins such as metallothionein (MT) [20,21]. In fact, HSPs are considered to be molecular chaperones which play a universal role in protecting the cells against the toxic effects of oxidative stress [12,[22][23][24].…”

“…In fact, HSPs are considered to be molecular chaperones which play a universal role in protecting the cells against the toxic effects of oxidative stress [12,[22][23][24]. As well MT, a cytosolic protein with high cysteine content, can function as a potent scavenger of ROS and it is considered as a mediator of cellular detoxification of metals in defense mechanisms to toxicity [20,21].…”

Gene expression‐based in vivo and in vitro prediction of liver toxicity allows compound selection at an early stage of drug development

“…These genes are known to play roles in the defense to oxidative stress and tissue damage and are often seen when tissue regeneration and proliferation occur [23][24][25][26][27][28]. Other genes involved in stress response and proliferation, such as glutathione peroxidase 2, microsomal epoxide hydrolase 1, aldo-keto reductase 7a3, or nucleosome assembly protein 1-like 1, were persistently induced throughout the experiment [29][30][31][32].…”