Genetic associations and serum paraoxonase levels with atherosclerosis in western Iranian patients.

The oxidative modification of low-density lipoprotein (LDL) in the arterial wall plays a pivotal role in the initiation and progression of atherosclerosis which is a complex and progressive disorder. Paraoxonase1 (PON1), which is required for lipid metabolism, is believed to protect LDL from oxidation. The relationship between PON1 gene Leusin55Methionin (L55M) and Glutamine192Arginine (Q192R) polymorphisms in western Iranians with atherosclerosis and its association with enzyme activity and oxidized low-density lipoprotein (oxLDL) were examined in the present study. In this study, blood specimens were collected from 145 healthy individuals and 154 patients with atherosclerosis proven by angiography referred to Shahid Madani Hospital, Khorramabad, Iran. Genomic deoxy ribonucleic acid (DNA) was extracted from whole blood. For all the subjects, restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was carried out for the detection of L55M and Q192R polymorphisms. PON1 enzyme activity and the level of oxLDL were also evaluated. There was a 3.114-fold increase in the risk of developing atherosclerosis in the subjects presenting the PON1L55M, MM genotype compared to those with the LL genotype (OR 3.114; 95% CI 1.412-6.870). PON1Q192R polymorphism in the PON1 gene was not associated with atherosclerosis. Patients with atherosclerosis had significantly higher oxLDL and reduced PON1 enzyme activity (P < 0.05) compared to the controls. There was no association between the type of genotype, enzyme activity, and oxLDL level. It has been concluded that PON1L55M polymorphism and MM genotype are associated with an increased risk of coronary artery disease (CAD) in Iranian patients with atherosclerosis. We did not find any relationship between PON1Q192R polymorphism and atherosclerosis.

Study of angiotensin-converting enzyme insertion/deletion polymorphism, enzyme activity and oxidized low density lipoprotein in Western Iranians with atherosclerosis: a case-control study.

BACKGROUND: It has been indicated that Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) polymorphism (rs4646994) could be regarded as a genetic factor that raises the risk of CAD through its impact on the activity of Angiotensin-Converting Enzyme (ACE) and angiotensin II level. The present study seeks to examine the relationship between ACE I/D polymorphism with the risk of atherosclerosis. Moreover, its potential effects on ACE activity and oxLDL level are investigated. METHODS: In this study, 145 healthy individuals and 154 patients (143 males and 156 females) were selected among the subjects referred to Shahid Madani Hospital. Atherosclerosis was determined in all subjects with gold standard angiography. Blood samples were collected, used to isolate white blood cells (WBC) and serum separation. The DNA was extracted and the polymorphism was determined by polymerase chain reaction (PCR). The enzyme activity was measured using high-performance liquid chromatography (HPLC). RESULTS: This study indicated that patients with atherosclerosis had higher levels of oxidized Low-Density Lipoprotein (oxLDL) and ACE activity (P < 0.05) as compared to controls. Although we found a significant association between ACE I/D polymorphism genotype and the allele with atherosclerosis in the male group, there were no association when the entire patient group was compared to the entire control group. CONCLUSION: Our study revealed the ACE I/D polymorphism of the ACE gene may not be an independent risk factor in the development of atherosclerosis and evaluation of ACE activity level is more important in evaluating the risk of disease. The researchers found no relation between ACE I/D polymorphism and atherosclerosis and also between types of genotype, ACE activity, and OxLDL level.

Exogenous glutamine ameliorates diabetic nephropathy in a rat model of type 2 diabetes mellitus through its antioxidant and anti-inflammatory activities.

This study aimed to evaluate the effects of glutamine (Gln) on diabetic nephropathy and other complications in a rat model of type 2 diabetes mellitus. Streptozotocin/nicotinamide induced diabetic rats were enrolled as an animal model of type 2 diabetes mellitus. Animals were divided into control, diabetic, and Gln (1000 mg/l in drinking water, eight weeks) treated diabetic groups. Gln alleviated renal inflammatory and oxidative stress biomarkers (tumour necrosis factor-alpha, interleukin 6, glutathione peroxidase, total superoxide dismutase, and glutathione), decreased serum uric acid and creatinine, and restored renal histopathological changes (glomerular volume, sclerosis, and leukocyte infiltration). Additionally, Gln ameliorated other complications, including systemic oxidative stress (serum malondialdehyde and nitric oxide, serum and liver glutathione, glutathione peroxidase, and total superoxide dismutase, and liver catalase), insulin resistance, hyperglycaemia, and hyperlipidaemia. Collectively, Gln attenuates diabetic nephropathy and other complications in type 2 diabetes mellitus in rats through its antioxidant and anti-inflammatory activities.

Ameliorative effects of histidine on oxidative stress, tumor necrosis factor alpha (TNF-α), and renal histological alterations in streptozotocin/nicotinamide-induced type 2 diabetic rats.

OBJECTIVES: The present study sought to evaluate the beneficial effects of histidine (His) on oxidative stress, tumor necrosis factor alpha (TNF-α), renal histological alterations and anti-oxidant enzymes gene expressions in type 2 diabetic rats. MATERIALS AND METHODS: Streptozotocin/nicotinamide (STZ/NA) induced diabetic rats were used as an animal model of type 2 diabetes. One group of rats received daily His (1000 mg/l) in drinking water for 8 weeks, whereas other groups (control and untreated diabetic groups) received only water. Different parameters such as glucose, insulin, insulin resistance, lipid profile, cardiac risk ratios, renal functional markers, and oxidative stress were determined in all groups. Moreover, renal histological alterations, mRNA expressions of anti-oxidant enzymes, and TNF-α were evaluated in the rats. RESULTS: His exhibited a protective effect on glucose, insulin, insulin resistance, lipid profile, cardiac risk ratios, renal functional markers, oxidative stress, and TNF-α. Furthermore, His restored the renal histological alterations and normalized the augmented mRNA expressions of renal anti-oxidant enzymes (glutathione peroxidase (GPX) and Cu-Zn superoxide dismutase (Cu-Zn SOD)) and TNF-α. CONCLUSION: His could ameliorate diabetes complications related to oxidative stress, inflammation, dyslipidemia, hyperglycemia, insulin resistance, and nephropathy. Hence, the use of this amino acid is recommended for diabetic patients in order to reduce diabetes complications.

The Protective Role of Gallic Acid Pretreatment On Renal Ischemia-reperfusion Injury in Rats.

BACKGROUND: Renal ischemia-reperfusion injury (RIR) occurs when there is a temporary restriction of blood flow to the kidneys followed by an influx of blood, re-oxygenating the tissues. This occurs as a severe complication of major surgery. This process causes significant damage to the tissues and is responsible for the development of acute kidney injury (AKI), a life-threatening condition with high mortality rates. Here, we evaluated the potential protective effects of the antioxidant, gallic acid (GA), on RIR in an in vivo rat model. METHODS: Adult male Sprague Dawley rats were randomly divided into three groups: group 1 (control, n = 8), group 2 (Ischemia-reperfusion (IR) with no-treatment, n = 7), and group 3 (IR + daily GA 100 mg/kg i.p, n = 7). The abdomens of the rats in the control group were opened during the surgical procedure, then sutured closed. GA pretreatment began daily 15 days prior to inducing RIR. To induce RIR, the umbilical arteries were obstructed on both sides and clamped with mild pressure for 45 min. Following the 45 min ischemia, the clamps were removed to allow for the induction of reperfusion. The reperfusion phase was 24 hours. RESULTS: Following IR, the serum levels of urea and creatinine significantly increased compared to the controls. Pretreatment with GA was observed to reduce urea and creatinine levels following IR. However, this decrease was not statistically significant. The serum and renal levels of malondialdehyde (MDA) in the IR group was significantly elevated compared to the control group. Conversely, glutathione (GSH) levels and the activity of glutathione peroxidase (GPX) significantly decreased in the IR group compared to controls. Our findings show GA pretreatment to significantly improve the levels of renal MDA, serum GSH, and GPX activity following RIR. CONCLUSION: Our findings highlight the protective role for GA in mitigating the damage caused by RIR and its applications as a potential treatment.

The Relation between Polymorphisms in Exon 5 and Exon 6 of GSTP1 Gene and the Risk of Lung Cancer in Iranian People

Objective: The GSTP1 gene, which is located on chromosome 11q13, consists of 7 exons and 6 introns. There are two polymorphisms in GSTP1 that have been exposed to a transposition for codon 105 (Ile/Val) and 114 (Ala/Val) in exons 5 and 6, which have been studied previously in relation to lung cancer. Since the level of GSTP1 expression in lung tissues and other human epithelial tissues is high, GSTP1Val-105 polymorphism is recognized as a sensitive factor for tobacco-related cancers, especially lung cancer. Methods: One hundred and twenty tissue block samples of patients with lung cancers and 120 peripheral blood samples of the control group were obtained from two referral cancer centers in Tehran, Iran, from 2011 to 2016. Genomic DNA was extracted from tissue blocks and buffy coat of study cases to detect SNP of GSTP1 gene using Tetra-primer ARMS-PCR. Results: There was a notable correlation between the incidence of lung cancer and variant Val105 (P-value=0.001; OR=2/6; 95% CI=1.49-4.53) and Ile105 (P-value=0.003; OR=0.41; 95% CI=0.23-0.73). The odds ratio for lung cancer in the homozygous Ile105/Ile105 genotype was 3.56 times higher than that of individual with heterozygous Ile105/Val105 (P-value<0.001; OR=3/56; 95% CI=1.826-6.934) genotype, that was statistically significant. Furthermore, the results showed that there was no significant correlation between Ala114/Val114 genotypes and lung cancer. The BC (P-value=0.007; OR=0.16; 95% CI=0.04-0.61) and AA (P=0.001) genotypes were statistically significant (P-value <0.05); and for those who had AA genotype, the odds ratio was almost six times higher than those with BC genotype. Conclusions: The study of GSTP1 polymorphisms indicated that unlike the polymorphism in exon 5, the GSTP1 exon 6 polymorphism correlated with the lung cancer risk in the select group of Iranian people. Likewise, the potential use of this genetic polymorphism as a lung cancer predictor is confirmed.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) Polymorphisms and Lung Cancer Risk among a Select Group of Iranian People

Objective(s): Lung cancer, caused primarily by smoking, is one of the leading determinants of mortality throughout the world. Here we investigated the effects of polymorphisms in two enzymes, i.e., GSTT1 and GSTM1, related to the antioxidant defense line against carcinogens associated with lung cancer among a select group of Iranian people. Materials and Methods: One hundred and twenty lung cancer patients from two referral centers in Tehran, Iran, were recruited for comparison with 120 healthy controls. Genomic DNA was extracted from the FFPE tumor tissues of the select cases and peripheral blood buffy coats of healthy controls. The polymorphisms of GSTT1 and GSTM1 were investigated by multiplex polymerase chain reaction. Results: With the 240 samples studied, no specific relationship with lung cancer was discerned for the GSTM1 (P=0.35; OR=1/33; 95% CI=0.79-2.25) polymorphism, but the GSTT1 (P=0.005; OR=2.4; CI=1.32-4.35) gene polymorphism revealed a notable association on logistic regression, taking into account age and sex factors. Furthermore, the GSTT1 genotype distribution in patients with LSCC was different from that of healthy cases (P=0.006; OR=3.11; CI=1.38-7.04). The risk of developing lung cancer with the T0M1 genotype was 3.46 times higher than with T1M1 genotype (P=0.002; OR=3.46; CI=1.61-7.46). Moreover, the risk of developing LSCC cancer in people with T0M1 genotypes was significantly elevated (P=0.004; OR=4.5; CI=1.62-12.52). Conclusion: Unlike GSTM1, the GSTT1 genotype distribution is associated with the incidence of lung cancer in Iranian people. Different types of lung cancer appear to show various correlations with GST polymorphisms in this regard.

Renoprotective Effects of Gallic Acid Against Gentamicin Nephrotoxicity Through Amelioration of Oxidative Stress in Rats

Abstract Gallic acid (GA), as a strong antioxidant, was selected in this study to investigate its possible nephroprotective effects against gentamicin (GM)-induced nephrotoxicity. Twenty-four rats were separated into three groups (n=8): group 1 (control group) received saline (0.5 mL/day), group 2 (GM group) received GM (100 mg/kg/day), and group 3 (treated group) received GM (100 mg/kg/day) and GA (100mg/kg/day). All treatments were performed intraperitoneally for 12 days. After 12 days, the rats were euthanized, and kidneys were removed immediately. For serum preparation, blood samples were collected before killing. Kidney paraffin sections were prepared from one of the kidneys and stained by the periodic acid-Schiff process. GA significantly decreased GM-induced renal histopathological injuries, including tubular necrosis, tubular cast, and leucocyte infiltration compared with the GM group. Additionally, GA significantly improved proteinuria, serum levels of urea and creatinine, and serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with nephrotoxic animals. Furthermore, GA caused a significant improvement in the levels of cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and cardiac risk ratios 1 and 2 in comparison with nephrotoxic animals. GA administration was observed to significantly improve the levels of lipid peroxidation, nitric oxide (NO), and glutathione (GSH) compared with the GM group. Finally, the activities and gene expression levels of catalase (CAT) and glutathione peroxidase (GPX) significantly increased following GA administration compared with the GM group. Our results indicated that GA has potential protective effects against GM nephrotoxicity by reducing oxidative stress in rats.