Oxidant and antioxidant of arylesterase and paraoxonase as biomarkers in patients with hepatitis C virus Ehab M.M. Ali a, ⁎ , Hanan Hussien Shehata b , Randa Ali-Labib b , Lamia M. Esmail Zahra a a Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Egypt b Biochemistry Department, Faculty of Medicine, Ain Shams University, Egypt Received 2 April 2009; received in revised form 1 June 2009; accepted 4 June 2009 Available online 16 June 2009 Abstract Objectives: Oxidative stress plays a role in the pathogenesis in patients with HCV infection. The objective of this study was to evaluate oxidant and antioxidant biomarkers in patients with HCV. Design and methods: Serum malonaldehyde (MDA) and nitric oxide (NO) levels and the activities of myeloperoxidase (MPO), arylesterase (AE) and paraoxonase-1 (PON1) were determined in 23 chronic and 21 cirrhotic patients with HCV and 21 healthy subjects. Results: Cirrhotic patients with HCV had higher serum NO level and MPO activity while lower AE and PON1 activities than the chronic. Significant inverse correlation was observed between MDA and PON1 activity in patients with HCV. The most significant HCV biomarker was MDA, AE, NO and PON1. The best combined ones for sensitivity, specificity were MDA + albumin, PON1 + AST, and PON1 + albumin. Conclusions: The use of the MDA, MPO, AE, NO and PON1 as biomarkers might be useful tools, helping in the monitoring of patients with HCV. © 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Keywords: Oxidative stress; Malondialdehyde (MDA); Nitric oxide (NO); Myloperoxidase (MPO); Arylesterase (AE); Paraxonase (PON1); Hepatitis C virus (HCV) Introduction Hepatitis C virus (HCV) infection is a major worldwide health problem that has an increasing prevalence and mortality, with more than 170 million people infected. Approximately 70– 80% of infected individuals develop chronic HCV infection. The hallmarks of chronic HCV infection are inflammation and liver fibrosis and 20–30% of patients develop cirrhosis with a risk of hepatocellular carcinoma [1]. Egypt has the highest prevalence HCV genotype-4 with more than 19% of the population infected and chronic HCV representing one of the top five leading causes of death [2]. Hepatitis C virus has the capacity to generate substantial oxidative stress within hepatocytes. Subsequently, oxidative stress has been identified as a significant mechanistic pathway culminating in the development of hepatic cirrhosis, liver failure and liver cancer [3]. Reactive oxygen species (ROS) mediated liver injury may be triggered by lipid peroxidation. It leads to oxidative stress and contributes to the initiation and progress of liver damage [4]. Cytotoxic products of lipid peroxidation, such as malondialdehyde (MDA), may impair cellular functions including nucleotide and protein synthesis, which may play a role in hepatic fibrogenesis [5]. Nitric oxide (NO), synthesized from L-arginine by nitric oxide synthase (NOS), is a relaxing factor for the vascular endothelium that may mediate hepatic injury from ROS and lipid peroxidation products. Nitric oxide and superoxide radical interact to form peroxinitrite, which is an important mediator of free radical toxicity [6]. Nitric oxide is an important signaling molecule that acts in many tissues to regulate a wide range of physiological processes. Consequently, abnormal regulation and control of NO synthesis affect a number of important biological processes and are involved in a variety of diseases. The NO system disturbances appear to play a key role in the pathogenesis of chronic liver diseases [7,8]. The host immune response to HCV infected hepatocytes is responsible for liver injury and subsequent development of hepatic fibrosis. The cellular elements comprising the host immune response include neutrophils, macrophages (Kupffer cells) and lymphocytes. Neutrophils and Kupffer cells contain Available online at www.sciencedirect.com Clinical Biochemistry 42 (2009) 1394 – 1400 ⁎ Corresponding author. Fax: +20 40 3350804. E-mail address: ehab_1964@hotmail.com (E.M.M. Ali). 0009-9120/$ - see front matter © 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.clinbiochem.2009.06.007