Chronic Hepatotoxicity of Carbon Tetrachloride in HSP-70 Knock Out Mice

Abstract

Abstract:The chronic hepatotoxic effects of carbon tetrachloride (CCl 4 ) in heat-shock protein (HSP) 70 knock out (HSP70-/-) mice were examined. After repeated intraperitoneal injections of CCl 4 for six weeks, the level of ALT and weight ratio of the liver to body were lower in HSP70-/-mice than in the control (WT) mice. The levels of HSP25 and HSP47 were lowered in HSP70-/-mice as compared with WT mice. The grades of hepatic necrosis and neutrophil infiltration were not significantly different between HSP70-/-and WT mice. The collagen content was not affected significantly by CCl 4 treatment. Key words: CCl 4 , chronic hepatotoxicity, HSP-70, knock out mice oxidant stress and HSP70 mRNA suggests that the binding of HSP70 protein to other damaged proteins reduces the availability of HSP70 protein, thereby inducing HSP70 expression universally under stress conditions [8]. CCl 4 treatment increased HSP70 and HSP25 levels in murine livers [9]. Thus HSP70 and other stress proteins seem to be important for preventing the accumulation of aberrant proteins. Further, the elevation of HSPs was reported to result in cytoprotection from a variety of subsequent stresses [3]. The binding of HSP70 to damaged proteins is believed to assist in preventing their aggregation and promoting correct refolding ("molecular chaperoning"), as well as facilitating their degradation [1].

Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis

“…Assuming hepatocyte injury being the crucial KE without which fibrosis could not occur via this AOP, then simple investigation of in vitro hepatotoxicity could provide relevant information for potential fibrosis prediction without the need of highly elaborated cell models. The initial AOP case study was based on data of two prototypic fibrogenic chemicals, namely Carbon Tetrachloride (CCl4) (Basu, 2003;Brattin et al, 1985;Calabrese and Mehendale, 1996;Calabrese et al, 1993;Clawson, 1989Dalu and Mehendale, 1996;EPA, 2010;Feng et al, 2011;Jaeschke et al, 2013;Jang et al, 2008;Lee et al, 2004;Li L. et al, 2012;Li X. et al, 2013;Luster et al, 2000;2001;Lv et al, 2012;Masuda, 2006;Morio et al, 2001;Nagano et al, 2007;Natsume et al, 1999;Neubauer et al, 1998;Nissar et al,2013;Park et al, 2004;Recknagel, 1976;Simeonova et al, 2001;Tipoe et al, 2006;Weber et al, 2003;Zhu and Fung, 2000) and Allyl…”