The LEC rat: a useful model for studying liver carcinogenesis related to oxidative stress and inflammation

Abstract

Growing evidence indicates oxidative stress as a mechanism of several diseases including cancer. Oxidative stress can be defined as the imbalance between cellular oxidant species production and antioxidant capability shifted towards the former. Lipid peroxidation is one of the processes that takes place during oxidative stress. Lipid peroxidation products, such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), are closely related to carcinogenesis as they are potent mutagens and they have been suggested as modulators of signal pathways related to proliferation and apoptosis, two processes implicated in cancer development. Mechanisms by which oxidative stress leads to tumor formation are still under investigation. The need of suitable in vivo models that could reflect that inflammation-related human carcinogenesis is evident. In this regard, the mutant strain Long Evans Cinnamon-like (LEC) rat provides a promising model for investigation of the relationship between hepatitis induced by oxidative stress and hepatocarcinogenesis because it has been demonstrated to develop spontaneous liver tumor formation related to copper accumulation and oxidative stress. In this review, the findings regarding oxidative stress and its relation with liver pathologies in LEC rats are discussed; we focus on the mechanisms proposed for HNE carcinogenesis.

Investigation of the Antioxidant Status in Multiple Myeloma Patients: Effects of Therapy

“…ROS are free radicals and other molecules with unpaired electrons (such as O 2 . -and H 2 O 2 ) that are highly reactive and can react with biologic macromolecules, peroxidise lipids to form mutagenic MDA, modify the structure and function of proteins, and cause oxidative damage to DNA (Marnett et al, 2003;Márquez et al, 2007;Ottaviano et al, 2008). Under normal conditions, intracellular ROS are maintained at a low level by various enzyme systems which maintain the in vivo redox homeostasis.…”

Proteasome Activity Deregulation in LEC Rat Hepatitis: Following the Insights of Transcriptomic Analysis

“…Oxidation of biomolecules as DNA, lipids, and proteins has been extensively described (Marquez et al, 2007;Nair et al, 2005;Yamamoto et al, 1999;Yasuda et al, 2006). According to these observations, our analyses of microarray data show enrichment of genes that belong to Protein Metabolism and Nucleobase, Nucleoside, Nucleotide, and Nucleic Acid Metabolism established by GO classification.…”

“…The aim of this study was to examine on a global scale, the gene expression changes during hepatitis development and progression in relation to oxidative stress. In this context, Long-Evans Cinnamon-like (LEC) rats have been described as a good model for studying the relation between oxidative stress, hepatitis, and hepatocarcinogenesis (Marquez et al, 2007;Mori et al, 1994). LEC rats suffer from a spontaneous copper accumulation due to a deletion in the Atp7b gene responsible for liver copper excretion (Wu et al, 1994).…”

A Preliminary Operational Classification System for Nonmutagenic Modes of Action for Carcinogenesis

“…Inflammatory processes are also an important source of endogenous oxidants that are suspected to contribution to carcinogenic initiation (Babbar and Caesero, 2006;Marquez et al, 2007;Ohshima et al, 2005).…”