Biomarkers of the Antioxidant Response: A Focus on Liver Carcinogenesis

Abstract

Many studies have demonstrated the association of oxidative stress caused by excessive and sustained production of reactive species with chronic inflammatory conditions, neurodegenerative diseases, diabetes mellitus, atherosclerosis, and cancer. The main mechanism of redox control relies on the cellular antioxidant response. Nevertheless, oxidative stress and oxidative damage to biomolecules are events inherent to the process of carcinogenesis. Antioxidant response systems do not operate in isolation, as there is significant convergence among thermodynamically favored systems. Three main systems may be identified: glutathione, thioredoxins (TRX), and nicotinamide adenine dinucleotide phosphate (NADPH). Liver tumors frequently exhibit overexpression of one or more proteins belonging to the antioxidant system, for example, glutathione reductase (GSR), glutathione S-transferase P (GSTP), gamma-glutamyl transferase (GGT), glucose-6-phosphate dehydrogenase (G6PD), thioredoxin reductase (TXNR), NAD(P)H dehydrogenase [quinone] 1 (NQO1), and prostaglandin reductase 1 (PTGR1). The increased expression of these enzymes is suggested as biomarker that favors tumor development by stimulating proliferation, angiogenesis, and metastasis or by preventing cell death. The loss of expression of some antioxidant enzymes could be used as biomarkers too such as catalase (CAT) and superoxide dismutase (SOD). Therefore, the expression of these proteins shows predictive value for the prognosis and risk of liver cancer recurrence in patients. In this chapter, we discuss the most recent findings regarding the enzymatic antioxidant cellular response that occurs during liver carcinogenesis and how these systems could be used as biomarkers in the clinical practice.