Elsevier

Atherosclerosis

Volume 191, Issue 2, April 2007, Pages 397-402
Atherosclerosis

Assessment of paraoxonase and arylesterase activities in patients with iron deficiency anemia

https://doi.org/10.1016/j.atherosclerosis.2006.04.007Get rights and content

Abstract

Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated enzyme with three activities which are paraoxonase, arylesterase and dyazoxonase. We aimed to determine serum (a) paraoxonase and arylesterase activities and, lipid hydroperoxide (LOOH) levels in patients with iron deficiency anemia (IDA) (b) whether there is an association between the development of atherosclerosis and paraoxonase/arylesterase activities in patients with IDA. Twenty-five female with IDA and 22 healthy female as control were enrolled in the study. Serum basal/salt-stimulated paraoxonase and arylesterase activities were measured spectrophotometrically. LOOH levels were measured by ferrous oxidation with xylenol orange assay. Basal/salt-stimulated paraoxonase and arylesterase activities were significantly lower in patients with IDA than controls (p < 0.001; for all), while LOOH levels were significantly higher (p < 0.001). Our results show that paraoxonase and arylesterase activities, which have antiatherogenic capability, are decreased in patients with IDA. Reduced paraoxonase and arylesterase activities may play a role in pathogenesis of atherosclerosis through increased susceptibility to lipid peroxidation in patients with IDA.

Introduction

Iron deficiency anemia (IDA) is the leading cause of anemia worldwide, causing IDA in 500–600 million people [1]. Anemia is a pathologic condition in which there is a decrease in red blood cell mass or a decrease in the amount of hemoglobin. Further, iron deficiency affects also the production of other proteins containing Fe2+, such as cytochromes, myoglobin, catalase, and peroxidase [2]. Therefore, IDA is associated with prematurity and low birth weight during pregnancy, defects in cognitive and psychomotor development during childhood, and impaired work capacity in adulthood [3], [4].

Paraoxonase-1 (PON1) was first detected in immunoprecipitates of high-density lipoprotein (HDL) after electrophoresis of human serum in 1961 [5]. PON1 is a HDL associated enzyme with three activities which are paraoxonase, arylesterase and dyazoxonase [6] and is a Ca2+-dependent serum esterase that is synthesized in the liver and is a protein of 354 amino acids (43 kDa) [7]. Since it catalyzes the hydrolysis of many organophosphates and aromatic carboxylic acid esters, it is considered to play an important role in the metabolism of many xenobiotic compounds such as insecticides (paraoxon and diazoxon), and nerve gases (sarin, soman, and tabun) [8]. Other synthetic esters such as phenyl acetate are also hydrolysed with a high catalytic efficiency [9].

Atherosclerosis is now a major health problem in many industrialized countries and contributes significantly to morbidity and mortality. Numerous epidemiological studies have revealed that hypercholesterolemia, hypertension and smoking are major risk factors for atherosclerosis [10]. Further, several studies suggested that PON1 activity is reduced in subjects with coronary artery disease [11], hypercholesterolemia [12], type 2 diabetes [12] and renal failure [13]. On the other hand, PON1 has been implicated in lipid metabolism, since as a HDL associated an antioxidant enzyme it can prevent lipid peroxide accumulation in low-density lipoproteins that are involved in the initiation of atherosclerosis [14], [15]. This may partly explain how HDL protects low-density lipoprotein (LDL) from oxidation. Oxidized LDL plays an important role in the initial stage of atherosclerotic lesions [16]. In fact, the enzyme serum PON1 has an important role in prevention of atherosclerosis. [17].

Epidemiological studies have revealed a wide variation in serum PON1 activity among individuals [18] PON1 presents at least five polymorphisms in the promoter region at positions −108 (T/C), −126 (G/C), −162 (A/G), −832 (G/A), and −909 (C/G), from which −108, −162, and −909 have been related with differences in PON1 activity and expression [19], [20]. Additionally, the PON1 gene has two coding region polymorphisms (R/Q 192 and M/L 55) [21]. The polymorhisms affect the hydrolytic activity of the PON1 isoenzymes with respect to certain substrates, such as paraoxon and lipid peroxides [22], [23]. The position 192 polymorphisms is the major determinant of the PON1 activity polymorphisms. However, the position-55 polymorphisms also exerts a smaller, but significant, effect on activity [22], [23]. These genetic polymorphism have been suggestion to be an independent risk factor for coronary artery disease [24], [17]. It has been suggested that low PON1 activity is related to coronary heart disease and that this activity, usually measured using paraoxon as a substrate, is under genetic and environmental regulation and appears to vary widely among individuals and populations [11].

To our knowledge, there is no data concerning the paraoxonase and arylesterase activities in patients with IDA. In addition, it is still unknown whether there is any relationship between the paraoxonase and arylesterase activities and atherosclerosis in patients with IDA. In the lightening of these data, we aimed to determine (a) paraoxonase and arylesterase activities as antioxidants and lipid hydroperoxide (LOOH) levels as an oxidative stress indicator in patients with IDA (b) whether there is any association between the development of atherosclerosis and paraoxonase/arylesterase activities in patients with IDA.

Section snippets

Subjects

The study was conducted at Harran University, School of Medicine, Department of Internal Medicine between 2004 and 2005. Twenty-five female with IDA and 22 healthy female were enrolled in the study. All subjects were informed about the study protocol and written consents were obtained from all participants.

Iron deficiency was defined as serum ferritin concentration <15 μg/L, indicating depleted iron stores; iron deficiency was defined as Hb < 10 g/dl and a mean corpuscular volume (MCV) < 80 fl and a

Results

Demographic and clinical data of the subjects are shown in Table 1. There were no significant difference between IDA subjects and controls in respect to age, gender, and body mass index (BMI) (all p > 0.05).

There were no significant difference between patients with IDA and controls in respect to serum TG and TC levels (p > 0.05 both of), while LDL-C levels were significantly higher in patients with IDA (p < 0.05). In contrast, HDL-C levels were significantly lower in patients with IDA compared to

Discussion

The organism has antioxidative mechanisms to overwhelm oxidants. In some conditions, oxidants increase and antioxidants decrease and antioxidative mechanisms may be exiguous to prevent oxidative damage completely. Consequently, oxidative stress develops [28]. Erythrocytes are equipped with a highly effective antioxidant defense system. They possess highly active antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and catalase (CAT). Oxidant levels and

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