Association of two common single nucleotide polymorphisms [SNPs +45T/G and +276G/T] of ADIPOQ gene with coronary artery disease in Type 2 Diabetic patients

Background: Adiponectin, an adipocyte-secreted hormone, is known to have anti-atherogenic, anti-inflammatory, and anti-diabetic properties. In the present study, the association between two common single nucleotide polymorphisms [SNPs] [+45T/G and +276G/T] of ADIOPQ gene and coronary artery disease [CAD] was assessed in the subjects with type 2 diabetes [T2DM]

Methods: Genotypes of two SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism in 200 subjects with T2DM [100 subjects with CAD and 100 without CAD]

Results: The frequency of TT genotype of +276G/T was significantly elevated in CAD compared to controls [X2=7.967, P=0.019]. A similar difference was found in the allele frequency of +276G/T between two groups [X2=3.895, P=0.048]. The increased risk of CAD was associated with +276 TT genotype when compared to reference GG genotype [OR=5.158; 95% CI=1.016-26.182, P=0.048]. However, no similar difference was found in genotype and allele frequencies of SNP +45T/G between two groups. There was a CAD protective haplotype combination of +276 wild-type and +45 mutant-type allele [276G-45G] [OR=0.37, 95% CI=0.16-0.86, P=0.022] in the subject population

Conclusion: Our findings indicated that T allele of SNP +276G/T is more associated with the increased risk of CAD in subjects with T2DM. Also, a haplotype combination of +45G/+276G of these two SNPs has a protective effect on the risk of CAD

Human sperm quality and metal toxicants: protective effects of some flavonoids on male reproductive function

Background: Metals can cause male infertility through affection of spermatogenesis and sperm quality. Strong evidences confirm that male infertility in metal-exposed humans is mediated via various mechanisms such as production of reactive oxygen species [ROS]. Flavonoids have antioxidant and metal chelating properties which make them suitable candidates for neutralizing adverse effects of metals on semen quality. In the current study, we have evaluated the effects of five types of flavonoids [rutin, naringin, kaempferol, quercetin, and catechin] on recovery of sperm motility and prevention of membrane oxidative damage from aluminum chloride [AlCl3], cadmium chloride [CdCl2], and lead chloride [PbCl4]

Materials and Methods: In this experimental study, motility and lipid peroxidation of metalexposed sperm was investigated in the presence of different concentrations of five kinds of flavonoids. Malondialdehyde [MDA] production was assessed as a lipid peroxidation marker

Results: Aluminum chloride [AlCl3], cadmium chloride [CdCl2], and lead chloride [PbCl4] diminished sperm motility. Treatment of metal-exposed sperm with rutin, naringin, and kaempferol attenuated the negative effects of the metals on sperm motility. Quercetin and catechin decreased the motility of metal-exposed sperm

Conclusion: Based on the MDA production results, only AlCl3 significantly induced lipid peroxidation. Treatment with rutin, naringin, and kaempferol significantly decreased MDA production

relationship between -2548 G/A leptin gene polymorphism and risk of breast cancer and serum leptin levels in ahvazian women

Potential association of leptin [LEP] gene polymorphisms has been suggested in the processes leading to breast cancer initiation and progression. We investigated whether genetic variations in the LEP -2548G/A gene are associated with risk of breast cancer. This case-control study consisted of 100 breast cancer cases and 100 control subjects without breast cancer that matched for age and body mass index [BMI]. Genotyping of LEP -2548G/A polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] assay. Serum leptin level was determined by ELISA in all study subjects. The genotype distributions [AA, AG, and GG] were 36, 55, and 9% in breast cancer cases and 52, 45, and 3% in control group, respectively. The frequency of LEP -2548 GG genotype was significantly elevated in breast cancer cases as compared to controls [chi2=6.90, p=0.032]. Similar difference was also found in allele frequencies between two groups [chi2=5.65, p=0.017]. A markedly increase risk of breast cancer was associated with the LEP -2548GG genotype when compared to the LEP -2548 AA genotype [OR=4.33, 95% CI=1.09-17.22]. In addition, postmenopausal women who bear at least one LEP -2548 G allele were at a markedly increased risk of breast cancer after adjusting for age and BMI confounders [OR=12.24, 95% CI=1.13-131.73]. The LEP -2548 G/A polymorphism is associated with markedly increased risk of breast cancer especially in postmenopausal Ahvazian women and supported the hypothesis that leptin is involved in breast cancer

effect of cigarette smoking on human sperm creatine kinase activity: as an ATP buffering system in sperm

Spermatozoa are a group of cells that consume adenosine triphosphate [ATP] rapidly. Creatine kinase [CK], produced by creatine phosphate, is an energy reservoir for the rapid buffering and regeneration of ATP and can play an important role in sperm motility. Therefore, this study investigates the effects of cigarette smoking on human sperm CK activity in males who smoke. In this case - control study, we obtained semen samples from male smokers [n=64] and nonsmokers [n=83]. Smokers were categorized as light, moderate, or heavy smokers according to the daily number of cigarettes smoked and the number of years they have smoked. Data were analyzed by the independent t test and Pearson's analysis. This investigation showed significantly lower sperm CK activity and movement in male smokers compared to nonsmokers. In addition, it was demonstrated that cigarette smoking had a dose-dependent effect on these parameters. There was a positive relation, although not significant, between sperm CK activity and its motility in male smokers. Smoking, by diminishing sperm CK activity, may potentially impair sperm energy homeostasis and have an association with damage to sperm motility. This effect can be an important mechanism that may cause infertility in male smokers. However, further research is necessary to elucidate the underlying mechanism of sperm motility damage caused by cigarette smoking

Lipid peroxidation and nitric oxide levels in male smokers' spermatozoa and their relation with sperm motility

Nitric oxide [NO] is synthesized from L-arginine by a family of en-zymes known as nitric oxide synthases. Low concentrations of NO is essential in biology and physiology of spermatozoa, but high amounts of NO is toxic and has negative effects on sperm functions. Moreover, sperm membrane contains high con-centrations of polyunsaturated fatty acids that are highly susceptible to oxidative damage that interferes with fertilization ability. Therefore, we investigated the cor-relation between levels of sperm malondialdehyde [MDA] and NO with sperm mo-tility in male smokers. Semen samples were collected from normozoospermic smoker [n=64] and nonsmoker [n=83] men. The content of sperm lipid peroxidation was determined by measuring malondialdehyde [MDA]. The sperm NO were also measured using Griess reagent. Data was analyzed by SPSS, [version 15.0], using independent t-test and Pearson analysis. The mean MDA and NO concentrations in the sperm of normozoospermic male smokers were significantly higher than the control group or normozoospermic nonsmokers, [p<0.001]. A significant negative relationship was noted between sperm motility and sperm MDA levels [r=?0.32, p=0.01]; and sperm motility and sperm NO concentration [for nitrite, r=?0.34, p=0.006 and for nitrate, r=?0.38, p=0.002]. It was concluded that the increase in MDA and NO production in sperm can influence sperm motility in normozoospermic smokers. Therefore, it seems that cigarette smoking may affect the fertility of male smokers via increasing the amount of sperm MDA/lipid peroxidation and NO concentrations

vitro effect of lead, silver, tin, mercury, indium and bismuth on human sperm creatine kinase activity: a presumable mechanism for men infertility

The aim of the present study was to investigate the in vitro effects of mercury [Hg[+2], lead [Pb[+2]], silver [Ag[+2]], tin [Sn[+2]], bismuth [Bi[+3]] and indium [In[+3] ions on sperm creatine kinase. creatine kinase was isolated from human sperm homogenates after chromatography on a DEAE cellulose column. At 60 microg ml[-1] metal concentration, 70% of the creatine kinase activity was inhibited by Hg[+2], while at the same concentration, Pb[+2], Ag[+2], Sn[+2], Bi[+3] and In[+3] caused 68%, 66.5%, 65.7%, 64.7% and 62.7% inhibition, respectively. All six metal ions displayed a competitive type of inhibition mechanism for the isolated creatine kinase as analyzed by Lineweaver-Burk plot. KA values of Hg[+2], Pb[+2], Ag[+2], Sn[+2], Bi[+3] and In[+3] were calculated and 8.34 mM, 5 mM, 4.54 mM, 3.45 mM, 3.12 mM and 2.63 mM values were obtained, respectively. All the studied metal ions, at levels of 60 micro g ml[-1], may reduce normal sperm metabolism by inhibition of sperm creatine kinase, which probably is an important cause of infertility in men. However, further investigations, as in vitro and in vivo, are needed to elucidate the exact mechanism of heavy metals on male reproductive functioning at the molecular level

Effects of grape seed proanthocyanidin extract on oxidative stress induced by diabetes in rat kidney

This study examined the effect of grape seed proanthocyanidin extract [GSPE] on lipid peroxidation content and activity of tissue antioxidant enzymes, including catalase, superoxide dismutase and glutathione peroxidase in diabetic rats. Thirty male rats were divided into three groups of 10 rats each: control, diabetic and diabetic groups that received 500 mg/kg GSPE for 6 weeks. Diabetes was induced by a single intraperitoneal injection of streptozotocin [50 mg/kg body weight]. Rats with fasting blood glucose levels above 250 mg/dl were used as diabetic animals. The first 24-hour urinary albumin excretion [UAE] was measured two weeks after diabetes induction and then each week until the end of the experimental period in all groups. Lipid peroxidation content and activities of catalase, superoxide dismutase and glutathione peroxidase were measured in kidney homogenate supernatants. Statistical significance of differences was assessed with one-way ANOVA by SPSS followed by Tukey's t-test. P <0.05 was assumed statistically significant. UAE in diabetic nephropathy rats were significantly higher than in control. In addition, an increase in lipid peroxidation content and decrease in catalase, superoxide dismutase and glutathione peroxidase activities in kidney of diabetic nephropathy rats were observed. The GSPE administration did not affect on body weight, but significantly decreased lipid peroxidation and augmented the activities of antioxidant enzymes studied in kidney of diabetic nephropathy rats as well as reduced UAE and decreased kidney weight. The results suggested that GSPE could ameliorate diabetic nephropathy rats through reduction of oxidative stress and increase in renal antioxidant enzyme activity

Influence of flavonols as in vitro on low density lipoprotein glycation

The non-enzymatic glycation of Low density lipoprotein [LDL] is a naturally occurring chemical modification of apolipoprotein B as a result of condensation between lysine residues and glucose. Glycated LDL is poorly recognized by LDL receptors and initiates different processes that can be considered proatherogenic. Thus, LDL glycation may contribute in the increased atherosclerotic risk of patients with diabetes. The objective of this study was to investigate the effect of naturally occurring flavonols on LDL glycation in vitro. In this study, LDL was isolated from EDTA-plasma by ultracentrifugation using a single step discontinuous gradient. Then, glucose was added to LDL and LDL glycation level was estimated in absence and presence of flavonols by sodium periodate assay. This study was showed that five flavonols: quercetin, myricetin, kaempferol, rutin and morin decreased LDL glycation in a dose-dependent manner. Also, it was demonstrated this nutrients decreased electrophoretic mobility of glycated LDL. The results of this investigation show that flavonols probably with their antioxidant properties inhibited LDL glycation and thus may have a role in ameliorating atherosclerotic risk of patients with diabetes mellitus

Effect of lycopene on formation of low density lipoprotein - copper complex in copper catalyzed peroxidation of low density lipoprotein, as in vitro experiment

A great deal of evidence has Indicated that oxidatively modified LDL plays a critical role in the initiation and progression of atherosclerosis. Antioxidants that can prevent LDL oxidation may act as antiatherogens. Copper is a candidate for oxidizing LDL in atherosclerotic lesions. The binding of copper ions 10 LDL is usually thought to be a prerequisite for LDL oxidation by copper. The aim of this study was to investigate effect of lycopene on copper bound to LDL and also effect of this binding on the susceptibility of LDL to oxidative modification. In this study, LDL was isolated from EDTA-plasma by ultracentrifugation using a single- step discontinuous gradient. Then lycopene was added to LDL and oxidizability of LDL was estimated by thiobarbitoric acid reactive substances [TBARS] after CuSo[4] addition. Finally, the effect of lycopene on formation of LDL-copper complex by gel filtration was studied. Our results showed that lycopene [as dose dependency] was suppressed the formation TBARS and LDL-copper complex. The lycopene with concentrations of 10 micro M, 50 micro M and 100 micro M was reduced susceptibility of LDL to oxidative modification approximately by 31, 67 and 71 percent, respectively. Furthermore, the addition of lycopene to the mixture containing LDL and copper before incubation was prevented the formation LDL-copper complex, approximately by 38 percent. The results of this I investigation show that lycopene with inhibition of binding of copper to LDL may decrease the susceptibility of LDL oxidation to this ion and thus may have a role in ameliorating atherosclerosis

Monitoring of serum nitric oxide in patients with acute leukemia

Nitric oxide [NO] is a molecule required for many physiological functions, produced from L-arginine by NO synthases [NOS]. It is a free radical, producing many reactive intermediates that account for its bioactivity. Sustained induction of the inducible form of NOS [iNOS] in chronic inflammation may be mutagenic, through NO-mediated DNA damage or hindrance to DNA repair, and thus potentially carcinogenic. Due to the short half-life of NO, usually its end products [nitrate or nitrite] are measured as an index of NO production. There is evidence that expression of iNOS in tumor cells, including acute myeloid leukemia and chronic lymphocytic leukemia increased. In this study, the levels of nitrate and nitrite [nitric oxide products] in the serum of patients with acute leukemia were determined. The serum levels of these compounds were measured in 40 acute leukemia patients. The results of serum nitrite and nitrate of patients were compared with corresponding values obtained in 40 healthy volunteers. These results indicate that patients with acute leukemia had a significant increase in the serum level of nitrite and nitrate