Stroke is an important public health problem and the third leading cause of death after coronary heart diesase and all cancers in all over the world. Free radicals and oxidative stress play important role in the pathogenesis of several diseases including atherosclerosis, stroke, cancer, neurodegenerative diseases such as Alzheimer&#039 / s dementia. The activity of paraoxonase (PON1) aganist phenylacetate is known as arylesterase (ARE). Paraoxonase is an esterase associated with high-density lipoprotein (HDL) and contributes to the protective role of this lipoprotein on low-density lipoprotein (LDL) oxidation. Oxidized LDL is known to play a central role in early events in the progression of atherosclerosis which is a risk factor for stroke. Glutathione S-transferases (GSTs) catalyze the conjugation of nonpolar compounds to reduced glutathione (GSH) and detoxify toxic metabolites produced within the cell by oxidative stress to protect cells from oxidant injury. v The maximum ARE enzyme activity was detected at 10 mM Tris-HCl buffer, pH 8.0 and at 45 &deg / C. ARE enzyme was saturated with its substrate phenylacetate around 20 mM concentration. The apparent Km and Vmax values of human blood serum ARE for phenylacetate were found as 1.66 mM and 3300 nmol/min/mg, respectively. The maximum GST enzyme activity was detected at 2 mM potassium phosphate buffer, pH 5.5 and at 65 &deg / C. GST enzyme was saturated with its substrate, CDNB around 4.5 mM concentration and with its cofactor, GSH around 8 mM concentration. The apparent Km and Vmax values of human blood serum GST for CDNB substrate were found as 2.8 mM and 0.43 nmol/min/mg and for GSH were found as 4.11 mM and 0.23 nmol/min/mg, respectively. In addition, effects of three different heavy metal ions, Cd+2, Hg+2 and Ni+2, on human blood serum ARE and GST activity were studied and half maximal inhibitory concentrations (IC50) were determined. The main objective of this study was to investigate the human blood serum ARE and GST activities in patient and control groups using the optimized conditions. For this purpose, blood samples were collected from 172 ischemic stroke patients and 105 controls. Then serum obtained from blood samples were used to determine ARE and GST activities. The mean of ARE activity in patient group (n=172, 109.9 &plusmn / 32.5 U/mL ) was insignificantly lower than the mean of ARE activity in control group (n=105, 113.5 &plusmn / 33.1 U/mL, P=0.284). GST activity of the patients (10.8 &plusmn / 4.4 U/L) was insignificantly higher than that of controls (10.5 &plusmn / 4.2 U/L, P=0.483 ). In addition, statistical analysis showed hypertension, diabetes and HDL as significant risk factors of stroke.

Stroke is the third leading cause of death. Atherosclerosis in the carotid arteries is a risk factor for ischemic stroke. Oxidized low density lipoprotein (LDL) plays a central role in the progression of atherosclerosis. Human paraoxonase 1 (PON1), a high-density lipoprotein (HDL) associated serum esterase/lactonase, protects HDL and LDL from oxidative modifications. Thus, PON1 is protective against the development of atherosclerosis. PON1 gene has two functional coding region (192Q/R and 55L/M) and one promoter region (&amp / #8722 / 107T/C) polymorphism that affect the catalytic efficiency and levels of the enzyme, respectively. In this study, the aim was to determine the importance of PON1 genetic polymorphisms and activity as risk factors for ischemic stroke. The study population was comprised of 172 unrelated adult Caucasian patients with acute hemispheric ischemic stroke and 105 symptom-free controls. Serum and total blood samples were obtained from G&uuml / lhane Military Medical Academy Hospital Neurology Department, Ankara. Hypertension and diabetes were 2 times more common and HDL-C was significantly lower among patients compared to controls. Logistic regression analysis revealed hypertension and smoking to be significant predictors of stroke. Serum PON1 activities towards three substrates, paraoxon (paraoxonase activity / PON), phenyl acetate (arylesterase activity / ARE) and diazoxon (diazoxonase activity), which were measured by spectrophotometric methods, were found to be lower in stroke patients compared to controls. PON and PON/ARE were negatively associated with ischemic stroke by use of logistic regression analysis. PON/ARE was 1.26 times protective against stroke. The frequencies of the risky alleles 192R, 55L and &amp / #8722 / 107T were increased in the patient group. Frequency of the 55L allele of PON1 was significantly increased among patients (0.690) compared to controls (0.628 / P=0.003). Logistic regression analysis revealed PON1 55LL genotype to be associated with a 1.8-fold increase in the risk of ischemic stroke versus control status. Prevalence of triple combined haplotype QRLMTC was significantly lower in stroke patients (4.1%) when compared to controls (11.4% / P=0.019). The combined heterozygote haplotype had around 7 times increased protective effect against stroke in the overall population and 10 times protective effect in the elderly population. The low expressor genotype &amp / #8722 / 107TT was associated with almost 2 times increased risk for stroke in elderly. 192R allele of PON1 represented 1.554 times increased risk for ischemic stroke in hypertensives relative to normotensives. Furthermore, the risk of hypertensive individuals having ischemic stroke was highest in the 192RR group (Odds Ratio / OR=7), followed by 192QR heterozygotes (OR=2.18), and the risk decreased to insignificant levels in 192QQ individuals. 192R allele constituted a 1.55 times increased risk in diabetics. 55L allele was associated with a 1.66 times increased risk of stroke in hypertensives and a 2.6 times increased risk for stroke in diabetics relative to non-diabetics. PON1 &amp / #8722 / 107T allele also represented a 1.35 times risk for stroke in hypertensives.