To investigate the protective effects and possible mechanism of pomegranate flowers polyphenols (PFP) on liver function of rats with diabetes combining non-alcoholic fat liver diseases, diabetes combining nonalcoholic fat liver disease model rats were established with high calorie feeding and small dose intraperitoneal injection of streptozotocin (STZ). Model rats were randomly divided into: model group, metformin group, pomegranate flowers polyphenols low, medium and high dose group (75, 150 and 300 mg x kg(-1)). After four weeks treatment, the levels of FPG, blood fat profiles and serum insulin, ALT, AST levels, SOD and MDA in the liver and serum separately were analyzed with biochemical methods. Paraoxonase (PON1 and PON3) mRNA and protein expression in liver were checked by RT-PCR and immunohistochemical method. Pathological changes of the liver were observed. FPG, IRI, non-HDL-C and transaminase significantly reduced and HDL-C raised in the each PFP dose group; Furthermore, compared with model group, fat drops in liver cells significantly reduced, antioxidant ability enhanced, PON1 mRNA and protein expression level in liver increased significantly. The protective effects of PFP against diabetes combining non-alcoholic fat liver diseases rats might through the increase liver PON1 mRNA and protein expression further enhanced the body antioxidant capacity and reduced IRI so as to ameliorate the rat hepatic steatosis.
Alanine Transaminase ; blood ; Animals ; Aryldialkylphosphatase ; genetics ; metabolism ; Aspartate Aminotransferases ; blood ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Fatty Liver ; metabolism ; pathology ; Flowers ; chemistry ; Insulin ; blood ; Liver ; metabolism ; pathology ; Male ; Malondialdehyde ; blood ; metabolism ; Non-alcoholic Fatty Liver Disease ; Plants, Medicinal ; chemistry ; Polyphenols ; isolation & purification ; pharmacology ; Punicaceae ; chemistry ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood ; metabolism

OBJECTIVETo investigate the association between the single nucleotide polymorphisms (SNPs) of paraoxonase-2 (PON2) gene and the susceptibility to occupational noise-induced deafness among Chinese Han population exposed to high noise levels [>85 dB (A)].

METHODSA case-control study was conducted in Chinese Han population exposed to high noise levels. The subjects were divided into case group (n = 127) and control group (n = 136) according to the Diagnostic criteria of occupational noise-induced deafness (GBZ 49-2007). The case group was composed of 127 workers with a mean binaural high-frequency hearing threshold not less than 40 dB, as measured using an electro-audiometer, while the control group was composed of 136 workers with a mean binaural high-frequency hearing threshold less than 40 dB, as measured using the electro-audiometer, who were on shift in the same position as the cases and matched with them for age, sex, and years of noise exposure. Peripheral venous blood (2 ml) was collected from each subject during physical examination to extract genomic DNA, and genotypes were identified using a TaqMan probe.

RESULTSPON2 genotypes rs7493 CG+GG, rs7785846 CT+TT, rs12026 CG+GG, and rs7786401 GT+TT were the risk factors for occupational noise-induced deafness, and the adjusted odds ratios (95%confidence intervals) were 5.87 (3.11∼11.07), 5.92 (3.10∼11.32), 5.53 (2.93∼10.45), and 5.93 (3.10∼11.34), respectively. In addition, the higher the noise exposure levels, the higher the risk of developing occupational noise-induced deafness among the individuals carrying mutant genotypes.

CONCLUSIONPON2 genotypes rs7493 CG+GG, rs7785846 CT+TT, rs12026 CG+GG, and rs7786401 GT +TT may be associated with the susceptibility to occupational noise-induced deafness among Chinese Han population exposed to high noise levels, and the effects of mutant genotypes and noise exposure levels may be mutually enhanced.

Adult ; Aryldialkylphosphatase ; genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Hearing Loss, Noise-Induced ; etiology ; genetics ; Humans ; Male ; Middle Aged ; Noise, Occupational ; adverse effects ; Polymorphism, Single Nucleotide ; Risk Factors

There is increasing evidence of a biochemical link between lipid oxidation and bone metabolism. Paraoxonase 1 (PON1) prevents the oxidation of low-density lipoprotein (LDL) and metabolizes biologically active phospholipids in oxidized LDLs. Here, we performed association analyses of genetic variation in PON1 to ascertain its contribution to osteoporotic fractures (OFs) and bone mineral density (BMD). We directly sequenced the PON1 gene in 24 Korean individuals and identified 26 sequence variants. A large population of Korean postmenopausal women (n = 1,329) was then genotyped for eight selected PON1 polymorphisms. BMD at the lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry. Lateral thoracolumbar (T4-L4) radiographs were obtained for vertebral fracture assessment, and the occurrence of non-vertebral fractures (i.e., wrist, hip, forearm, humerus, rib, and pelvis) was examined using self-reported data. Multivariate analyses showed that none of the polymorphisms was associated with BMD at either site. However, +5989A>G and +26080T>C polymorphisms were significantly associated with non-vertebral and vertebral fractures, respectively, after adjustment for covariates. Specifically, the minor allele of +5989A>G exerted a highly protective effect against non-vertebral fractures (OR = 0.59, P = 0.036), whereas the minor allele of +26080T>C was associated with increased susceptibility to vertebral fractures (OR = 1.73, P = 0.020). When the risk for any OFs (i.e., vertebral or non-vertebral) was considered, the statistical significance of both polymorphisms persisted (P = 0.002-0.010). These results suggest that PON1 polymorphisms could be one of useful genetic markers for OF risk in postmenopausal women.
Aged ; Alleles ; Aryldialkylphosphatase/*genetics ; Bone Density ; Female ; Gene Frequency ; Gene Order ; Genetic Markers ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Korea/epidemiology ; Linkage Disequilibrium ; Male ; Middle Aged ; Molecular Typing ; Osteoporotic Fractures/epidemiology/*genetics ; *Polymorphism, Genetic ; *Postmenopause ; Risk Factors

Paraoxonase 1 (PON1) hydrolyzes a number of toxic organophosphorous compounds and reduces lipid peroxide accumulation, and PON1 genetic polymorphisms in the coding region modulate serum PON1 activity. In this study, we investigated the association between 3 polymorphisms of PON1 located in intron 5 (17899insdelTT and 17974CT) and exon 6 (192QR) and serum PON1 activity. The genetic polymorphisms and serum activity of PON1 were analyzed in 153 healthy Koreans by using a direct sequencing assay and spectrophotometric method, respectively. A significant linkage disequilibrium (LD) was observed between all tested single nucleotide polymorphisms, with the strongest LD observed between 17899insdelTT and 192QR (D' = 0.984). The 17899insdelTT, 17974CT and 192QR genetic polymorphisms were associated with significant differences in serum paraoxonase activity. In multiple regression analyses, smoking, triglyceride level, high-density lipoprotein (HDL) level, and the 17899insdelTT and 192QR genetic polymorphisms were significant determinants of serum paraoxonase activity, while age, smoking, triglyceride level, HDL level, and the 192QR genetic polymorphism were significant determinants of serum arylesterase activity. These results suggest that although the 192QR genetic polymorphism in the coding region of PON1 is primarily associated with serum PON1 activity, the intronic polymorphisms are also involved in serum PON1 activity, and this association may be mediated by LD.
Aged ; Alleles ; Aryldialkylphosphatase/blood/*genetics ; Asian Continental Ancestry Group/*genetics ; Exons ; Female ; Gene Frequency ; Genotype ; Humans ; Introns ; Linkage Disequilibrium ; Lipoproteins, HDL/blood ; Male ; Middle Aged ; *Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Regression Analysis ; Republic of Korea ; Smoking ; Triglycerides/blood

It has been hypothesized that blood infusion of reconstituted HDL (rHDL) is a possible therapeutic strategy for the treatment of coronary artery disese. To compare short-term anti-inflammatory activity of wildtype (WT) apoA-I and point mutants, each rHDL containing WT, V156K, or R173C was infused into apo-E deficient atherosclerotic mice. Each rHDL was injected via the tail vein at a dosage of 120 mg/kg of body weight in 0.4 ml of tris-buffered saline (TBS), and blood was then collected at 24 and 48 h post-injection. Although regression activity was observed in each of the rHDL infused groups, a 30% reduction in the lipid-stained area of the aortic sinus was observed in the V156K and R173C-rHDL groups when compared to that of the WT-rHDL group, and this reduction was well correlated with an approximately 60% reduction in the accumulation of macrophages in the lesion area. Additionally, the groups that received the V156K and R173C-rHDL treatments showed smaller increases in the GOT, GPT, interleukin-6, myeloperoxidase (MPO) and lipid hydroperoxide (LPO) serum levels than those that received the WT-rHDL treatment. In addition, the strongest serum paraoxonase and ferric reducing ability was observed in the V156K and R173C-rHDL groups. In vitro nitration and chlorination of apoA-I by MPO treatment revealed that V156K-rHDL and R173C-rHDL were less susceptible to chlorination. Furthermore, rHDL treatment inhibited cellular uptake of oxidized LDL by macrophage cells and the production of proatherogenic species in culture media. In conclusion, blood infusions of the rHDLs exerted in vivo regression activity with anti-inflammatory and antioxidant activity in apo-E deficient mice and THP-1 cells, especially in those that were treated with V156K and R173C apoA-I.
Animals ; Anti-Inflammatory Agents/immunology/*therapeutic use ; Apolipoprotein A-I/blood/genetics/immunology/*therapeutic use ; Apolipoproteins E/genetics ; Aryldialkylphosphatase/blood/metabolism ; Atherosclerosis/*drug therapy ; Cell Line ; Cell Membrane Permeability ; Cholesterol/blood/metabolism ; Humans ; Lipoproteins, HDL/genetics/immunology/*therapeutic use ; Lipoproteins, LDL/metabolism ; Macrophages/cytology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxidation-Reduction/*drug effects ; Peroxidase/blood/metabolism ; Point Mutation

We constructed an expression cassette of the organophosphorus pesticide degrading (opd) gene under the control of the E8 promoter. Then opd was transformed into tomato fruit using an agroinfiltration transient expression system. beta-Glucuronidase (GUS) staining, reverse transcription-polymerase chain reaction (RT-PCR), wavelength scanning, and fluorescent reaction were performed to examine the expression of the opd gene and the hydrolysis activity on coumaphos of organophosphorus hydrolase (OPH) in tomato fruit. The results show that the agroinfiltrated tomato fruit-expressed OPH had the maximum hydrolysis activity of about 11.59 U/mg total soluble protein. These results will allow us to focus on breeding transgenic plants that could not only enhance the degrading capability of fruit and but also hold no negative effects on pest control when spraying organophosphorus pesticides onto the seedlings in fields.
Aryldialkylphosphatase ; genetics ; physiology ; Coumaphos ; pharmacology ; Insecticides ; pharmacology ; Lycopersicon esculentum ; genetics ; metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic

Paraoxonase (PON) has anti-atherogenic activity. Considering the important role of polymorphism in the genetic susceptibility to cardiovascular disease and the variability of its allele frequencies in different ethnic groups, the distribution of genotypes and allele frequencies of PON1M55L, PON1Q192R, PON2A148G, and PON2S311C polymorphisms was analyzed in a total 988 South-western Koreans and determined their effects on lipid parameters. The genotype distribution of PON1 at position 55 was LL=0.886, LM=0.114; and at position 192 was QQ=0.406, QR=0.594. The frequencies of the PON1 55L allele and the PON1 192R allele were similar to those seen in Chinese populations and Western populations, respectively. The genetic distribution of PON2 at position 148 was AA=0.619, AG=0.345, GG=0.035; and at position 311 was CC=0.035, SC=0.345, SS=0.619. The frequencies of the PON2 148G and 311S alleles were similar to those seen in Chinese populations. The concentrations of LDL and ApoB were significantly different between the PON2A148G (P<0.05) and PON2 S311C polymorphisms (P<0.01). PON polymorphisms and allele frequencies were described in Koreans living south-western part of Korea. These ethnic variations are considered important in the interpretation of diseases associated with PON polymorphisms.
Aged ; Apolipoproteins B/analysis ; Aryldialkylphosphatase/*genetics ; Asian Continental Ancestry Group/*genetics ; Cardiovascular Diseases/genetics ; Cholesterol, LDL/analysis ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Korea ; Male ; Middle Aged ; *Polymorphism, Genetic

OBJECTIVETo study the relationship between single nucleotide polymorphisms of paraoxonase 2 (PON2) and stroke.

METHODSObjects examined comprised of three groups: 120 healthy people, 150 patients with cerebral hemorrhage, 180 patients with cerebral infarction. The PON2 genotypes were determined with PCR and digested by specific restriction enzymes.

RESULTSC311S and G148A polymorphisms of PON2 gene existed among population of Chinese Hunan area, with the allele frequencies 0.23/0.77 for C/S and 0.57/0.43 for G/A in the control group. There was no significant difference of genotype and allele frequency between stroke patients and controls (P>0.05).

CONCLUSIONC311S polymorphism of PON2 has no significant correlation with stroke in Han people of Chinese Hunan area and allele C/S is not an independent risk factor for stroke,neither is G148A.

Aged ; Aryldialkylphosphatase ; genetics ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Stroke ; genetics

OBJECTIVETo investigate the relationship between paraoxonase (PON) polymorphisms and serum homocysteine thiolactone (HTL) and coronary heart diseases.

METHODIn this prospective study, serum complex of HTL levels using ELISA, and the lever of serum Hcy using high pressure liquid chromatography (HPLC), determined the PON1/T(-107)C and PON2/C311S genotypes using PCR-restriction fragment length polymorphisms 203 were measured in patients with angiographic documented coronary heart disease (CAD) and 117 controls.

RESULTSSerum levels of Hcy and the complex of HTL in CAD patients were significantly higher than that in controls (P < 0.05). No significant difference was found in frequencies of PON1/T(-107)C genotypes and alleles (P > 0.05) between CAD patient and controls. The PON2/C311S (SS) genotype was lower in CAD patients than that in controls (P < 0.05), while the frequency of allele was similar between the two groups (P > 0.05). The T allele of PON1/T(-107)C and S alleles of PON2/C311S polymorphism were associated with lower plasma Hcy and HTL complex [Hcy (11.83 +/- 4.76) micromol/L vs (15.32 +/- 10.32) micromol/L, P < 0.05; HTL complex (24.36 +/- 9.30) U/ml vs (32.05 +/- 10.44) U/ml, P < 0.05]. The genetype PON2 and allele C were higher in CAD patients with type 2 diabetes than that in CAD patients without type 2 diabetes and controls (P < 0.005).

CONCLUSIONSThe elevation of serum Hcy and the complex of HTL were associated with increased risk of coronary heart disease. The allele PON1/(-107)T and PON2/311S might be protective for the development of atherosclerosis.

Adult ; Aged ; Aryldialkylphosphatase ; genetics ; Coronary Disease ; blood ; complications ; genetics ; Cysteine ; blood ; Diabetes Mellitus, Type 2 ; complications ; Female ; Homocysteine ; analogs & derivatives ; blood ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic

BACKGROUNDOxidative stress such as low-density lipoprotein (LDL) oxidation is thought to be an important mechanism in Alzheimer's disease (AD). Paraoxonase 1 (PON1), an enzyme located on high-density lipoprotein, can prevent LDL from oxidation to some extent. It is also a potent cholinesterase inhibitor and an arylesterase, combating organophosphate poisoning and metabolization of environmental neurotoxins which might be responsible for neurodegeneration with aging. We evaluated the association of Gln192Arg polymorphism in the PON1 gene with AD in a Chinese Han ethnic population.

METHODSPatients and age-matched controls were recruited from outpatient clinics and a population-based epidemiological survey, respectively. Gln192Arg polymorphism in the PON1 gene was detected by allele-specific PCR technique in 521 patients with AD and 578 healthy controls.

RESULTSThe presence of at least one of PON1 R alleles (Q/R or R/R) was lower in AD patients than in the controls (82.7% vs 87.4%; chi(2) = 4.68, P = 0.03). PON1 gene R allele frequency was lower in AD patients than in the controls (60.7% vs 64.7%; chi(2) = 3.85, P = 0.05). One-way ANOVA showed that PON1 genotype had no effect on the age of onset for developing AD. Logistic regression analysis demonstrated the age and sex-adjusted odds ratio (OR) for the risk of AD in PON1 of PON1 R allele carriers was 0.71 (P = 0.044, 95% CI, 0.51 - 0.99).

CONCLUSIONOur results indicate that Gln192Arg polymorphism in the PON1 gene is associated with AD, and PON1 R allele might be a protective factor for AD in a Chinese Han ethnic population.

Aged ; Aged, 80 and over ; Alzheimer Disease ; genetics ; Aryldialkylphosphatase ; genetics ; China ; ethnology ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide