Association between the FABP2 Ala54Thr and CRP+1059C/G polymorphisms and small dense LDL level in patients with atherosclerosis: a case-control study.

BACKGROUND: The polymorphisms of fatty acid-binding protein 2 (FABP2) and C-reactive protein (CRP) might act as genetic risk factors for atherosclerosis. The study aimed to investigate the relationship between FABP2 Ala54Thr and CRP+1059C/G polymorphisms and atherosclerosis as well as the association of Small dense-LDL (sd-LDL). METHODS: A total of 255 subjects (125 controls and 130 patients) were included. The FABP2 and CRP polymorphisms were determined by PCR-RFLP and AS-PCR methods, respectively. Sd-LDL was measured based on Hirano et al method. RESULTS: There were no significant distinctions between the patient and control groups concerning FABP2 and CRP polymorphisms (p > .05). No significant relationship was observed between studied polymorphisms and sd-LDL level in the patient group (p > .05). However, patients group had higher level of sd-LDL compared to controls (p < .05). CONCLUSION: FABP2 Ala54Thr and CRP+1059G/C polymorphisms were not associated with atherosclerosis and sd-LDL level. However, the increased sd-LDL level was known as a risk factor for atherosclerosis.

Association of E-Selectin gene polymorphisms and serum E-Selectin level with risk of coronary artery disease in lur population of Iran.

BACKGROUND: Adhesion molecules like E-selectin have important role in pathogenesis of atherosclerosis. C1901T and G98T polymorphisms of E-selectin gene and E-selectin serum level may affect the risk of coronary artery disease (CAD). METHODS: A total of 145 normal individuals and 154 patients diagnosed with CAD from the Lur population of Iran undergoing coronary angiography were enrolled. Genetic polymorphisms of E-selectin were determined using PCR-RFLP. Serum level of soluble E-selectin was measured using Elisa. RESULTS: T allele in C1901T polymorphism was significantly associated with an increased risk of atherosclerosis (P = 0.018). No significant association was observed for G98T polymorphism. The mean serum level of soluble E-selectin in the patient group was significantly higher than the control group (P < 0.001). CONCLUSIONS: Allele type in C1901T polymorphism plays a role in increasing the risk of developing CAD. Furthermore, since serum E-selectin level is associated with systemic inflammation, it contributes to the increased risk of the disease.

Angiotensin-converting enzyme gene insertion/deletion polymorphism and hypertension disease.

Background: The renin-angiotensin system (RAS), which is important for controlling haemostasis in the body, can increase the development of essential hypertension (HTN). Various surveys have shown that ACE I/D polymorphism that influences ACE activity, a key component of RAS, has been known to be associated with the risk of HTN. The goal of this study was to investigate the correlation between ACE (I/D) polymorphism and HTN.Methods: Blood samples were obtained from 102 patients and 104 healthy individuals. The two groups were matched by age and sex. Informed consent was prepared for the study. The demographic data were collected using a questionnaire. White blood cells (WBCs) and then DNA were extracted from whole blood. After this, the PCR test was performed using specific primers. PCR products were examined using 1% agarose gel. Individuals with genotype II having a band of 490 bp, ID two band of 490 bp and 190 bp, and individuals with DD genotype, have a band in region 190 bp.Results: The average age of the patients was 52.7 ± 7.5 years. A significant difference was seen in the distribution of DD, II and I/D genotypes of ACE polymorphism between the essential hypertensive patients (44.1, 10.8, and 45.1%) and their ethnically matched healthy control (61.5, 3.8, and 24.6%, respectively). Our study showed an increased risk of disease in people with II genotype in comparison to ID and DD genotypes (0.46 (0.1-1.75) and 0.26 (0.05-0.94), respectively).Conclusions: The present study demonstrated that ACEI/D polymorphism is characterised with greater risk of essential HTN in the Lorestan province. II genotype increased the relative risk of essential HTN in the population. In the future, more investigations with more samples size are recommended for the better study of genetic factors in hypertensive patients.

Effects of Rosmarinic Acid on Methotrexate-induced Nephrotoxicity and Hepatotoxicity in Wistar Rats.

INTRODUCTION: Methotrexate (MTX), used in the treatment of cancerous patients, causes toxicity in the different organs of the body. This study of rosmarinic acid (RA) is as an antioxidant on nephrotoxicity and hepatotoxicity induced by MTX. METHODS: Rats (n = 32) were divided into four groups: sham; MTX; 100 mg\kg RA + MTX; 200 mg/kg RA + MTX. The amount of MTX was 20 mg/kg. 24 hours after injection of the last dose of MTX, the blood samples and kidneys and liver of rats were studied. The aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, serum creatinine were assessed. Tissue antioxidant enzymes and malondialdehyde (MDA) levels were measured. The liver and kidney tissues were histopathologically examined. RESULTS: MTX significantly increased the urea, creatinine, ALT, AST, ALP levels, and renal MDA and significantly decreased renal catalase (CAT), hepatic glutathione (GSH), and hepatic CAT activity. MTX induced necrosis, leukocyte infiltration, eosinophilic casts, glomerular damage in kidney tissue and necrosis, degeneration and cellular vacuolization in liver tissues. RA at 100 mg/kg caused a significant decrease in ALT and AST and at two doses significantly decreased urea, renal MDA, and liver MDA. RA at 200 mg/kg significantly increased the renal CAT and liver GSH. RA in two doses significantly decreased necrosis and Leukocyte infiltration. RA caused a significant decrease in degeneration and cellular vacuolization in liver tissues. CONCLUSIONS: RA with its antioxidant and anti-inflammatory characteristics decreased the MTX induced nephrotoxicity and hepatotoxicity.

Cinnamic acid ameliorate gentamicin-induced liver dysfunctions and nephrotoxicity in rats through induction of antioxidant activities.

This study was the first to evaluate the possible protective effects of cinnamic acid (CA) against Gentamicin (GM) induced liver and kidney dysfunctions in rats. Adult male Wistar rats were randomly assigned to 4 equal groups (n = 8): Control group (saline, 0.5 ml/day), CA group (CA, 50 mg/kg/day), GM group (GM, 100 mg/kg/day), and GM + CA group (100 & 50 mg/kg/day). Following 12 days of treatments, blood and 24 h urine samples were collected and kidneys were taken out for biochemical, histopathological, and molecular studies. Following CA treatment, renal function markers and transaminases activities including serum urea (59.92%) and creatinine (50.41%), protein excretion rate (43.67%), and serum activities of aspartate aminotransferase (AST) (54.34%) and alanine aminotransferase (ALT) (47.26%) significantly reduced in the treated group as compared with the GM group (P < 0.05). Also, CA could significantly ameliorate the levels of triglyceride (29.70%), cholesterol (13.02%), very low-density lipoprotein (29.69%) and high-density lipoprotein-cholesterol (7.28%). CA could also attenuate oxidative stress through a decrease of serum malondialdehyde (MDA) (50.86%) and nitric oxide (NO) (0.85%) and an increase of renal catalase (CAT) (196.14%) and glutathione peroxidase (GPX) activities (45.88%) as well as GPX mRNA expression (44.42-fold) as compared with the GM group (P < 0.05). Moreover, histopathological evaluations revealed attenuated tubular damages and reduced inflammatory cellular infiltration in CA treated animals. Overall, CA alleviates GM-induced nephrotoxicity and alterations in transaminases activities in rats through its antioxidant 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.

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.

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.

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.

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.