scholarly journals Role of CYP2E1 and NQO1 polymorphisms in oxidative stress derived cancer in Thais with and without dyslipidemia

2017 ◽  
Vol 9 (5) ◽  
pp. 601-611
Author(s):  
Pharrunrat Tanaviyutpakdee ◽  
Krongtong Yoovathaworn ◽  
Jintana Sirivarasai ◽  
Suwannee Chanprasertyothin ◽  
Pachara Panpunuan ◽  
...  

Abstract Background Hyperlipidemia can induce the endogenous production of reactive oxygen species (ROS), which may cause carcinogenesis. Cytochrome P450 (CYP) 2E1 activity, induced by various factors including polyunsaturated fatty acids, effects the incidence of cancers, whereas NQO1, a flavoprotein, may protect against ROS. Objectives To investigate the effect of CYP2E1 and NQO1 polymorphism on oxidative stress status in Thais with and without dyslipidemia. Methods We included 1380 apparently healthy employees of the Electricity Generating Authority of Thailand in this study. We determined their CYP2E1 and NQO1 genotypes and related these to blood lipid profiles, and circulating levels of antioxidant enzymes, malondialdehyde (MDA), and reduced glutathione (GSH). Lifestyle-related factors were determined from questionnaires. Results All tested genotype frequencies were in Hardy-Weinberg equilibrium. The heterozygous and variant genotype distribution and allele frequency of CYP2E1 *5B were less common than CYP2E1 *6. Heterozygous NQO1 was the most prevalent form. The frequency of the mutated allele CYP2E1 *5B was 0.16, CYP2E1 *6 was 0.22, and NQO1 *2 was 0.43. Significant differences were observed for blood cholesterol, triglyceride, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol between normolipidemic participants, and those with hypercholesterolemia, hypertriglyceridemia, and combined hyperlipidemia. Participants in the hyperlipidemic subgroup who bore any variant alleles of genes had higher plasma MDA and GSH levels, and superoxide dismutase and glutathione peroxidase activity, but lower catalase activity when compared with normolipidemic participants bearing wild-type alleles. Conclusions Variations in genetic disposition and dyslipidemia can modify oxidative stress status. Relatively more free radicals may be generated in individuals in subgroups with hyperlipidemia bearing any variant alleles.

Author(s):  
Ruihai Zhou ◽  
George A. Stouffer ◽  
Sidney C. Smith

Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as “bad” cholesterol and high-density lipoprotein cholesterol (HDL-C) as “good” cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.


2021 ◽  
Vol 10 (15) ◽  
pp. 3400
Author(s):  
Cathy Degroote ◽  
Roland von Känel ◽  
Livia Thomas ◽  
Claudia Zuccarella-Hackl ◽  
Jens C. Pruessner ◽  
...  

Hyperreactivity to stress may be one explanation for the increased risk of cardiovascular disease (CVD) in individuals with essential hypertension. We investigated blood lipid reactivity to the Montreal Imaging Stress Task (MIST), a psychosocial stressor, in hypertensive and normotensive men and tested for prospective associations with biological risk factors. Fifty-six otherwise healthy and medication-free hypertensive and normotensive men underwent the MIST. We repeatedly measured cortisol and blood lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)) immediately before and up to 1 h after stress. Lipid levels were corrected for stress hemoconcentration. Thirty-five participants completed follow-up assessment 2.9 ± 0.12 (SEM) years later. CVD risk was assessed by prospective changes in TC/HDL-C ratio, IL-6, D-dimer, and HbA1c from baseline to follow-up. The MIST induced significant changes in all parameters except TC (p-values ≤ 0.043). Compared with normotensives, hypertensives had higher TC/HDL-C-ratio and TG (p-values ≤ 0.049) stress responses. Blood lipid stress reactivity predicted future cardiovascular risk (p = 0.036) with increases in HbA1c (ß = 0.34, p = 0.046), IL-6 (ß = 0.31, p = 0.075), and D-dimer (ß = 0.33, p = 0.050). Our results suggest that the greater blood lipid reactivity to psychosocial stress in hypertensives, the greater their future biological CVD risk. This points to lipid stress reactivity as a potential mechanism through which stress might increase CVD risk in essential hypertension.


2021 ◽  
pp. 1-11
Author(s):  
Fabricio de Souza ◽  
Luciano Acordi da Silva ◽  
Gisele Santinoni Ferreira ◽  
Márcia Mendonça Marcos de Souza ◽  
Franciane Bobinski ◽  
...  

Purpose: This study evaluated the effects of 12 weeks of karate training on cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. Method: Seventy adolescents were randomized into 2 groups: control received nutritional and psychological interventions once a week for 12 weeks, and treatment received nutritional and psychological interventions once a week, plus 3 karate sessions per week, for 12 weeks. The main outcome measure was improvement in cardiometabolic parameters, oxidative stress, and inflammation. Results: After the intervention period, the treatment group showed a reduction in resting heart rate (77.86 [10.89]), high-density lipoprotein cholesterol (40.86 [8.31]), and triglycerides (75.18 [32.29]) and an increase in low-density lipoprotein cholesterol (95.64 [42.53]) in relation to pretraining. Regarding oxidative stress markers, there was a reduction in protein carbonylation (0.07 [0.06]) and nitric oxide (1.39 [1.11]) and an increase in superoxide dismutase (0.68 [0.31]) and glutathione (0.11 [0.08]) compared with pretraining. With respect to inflammation, adiponectin increased (14.54 [5.36]) after the intervention when compared with preintervention. Conclusion: The study concluded that the intervention may improve cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. Long-term effects need to be evaluated.


2013 ◽  
Vol 12 (5) ◽  
pp. 29-33
Author(s):  
S. A. Matveeva

Aim.To study the associations between blood lipid profile and blood glucose levels in men with coronary heart disease (CHD), stable effort angina (SEA), metabolic syndrome (MS), and Type 2 diabetes mellitus (DM-2).Material and methods.The study included 82 men (mean age 50,5±0,9 years) with CHD, Functional Class I–III SEA, MS, and DM-2. The following lipid profile parameters were assessed: total cholesterol (TCH), triglycerides (TG), low-density lipoprotein cholesterol (LDL–CH), very low-density lipoprotein cholesterol (VLDL–CH), high-density lipoprotein cholesterol (HDL–CH), atherogenic index (AI), and triglyceride index (TGI), together with fasting blood glucose.Results.There were positive (direct) associations between higher levels (>90th percentile) of lipid profile parameters (TCH, TG, LDL–CH, VLDL– CH, HDL–CH, AI, TGI) and blood glucose, as well as between lower levels (≤10th percentile) of lipid profile parameters (TCH, TG, LDL–CH, VLDL– CH, AI, TGI) and blood glucose. At the same time, there were negative (inverse) associations between lower lipid levels (≤10th percentile of TCH, TG, LDL–CH, VLDL–CH, HDL–CH, AI, TGI) and higher glucose levels (>90th percentile), as well as between higher lipid levels (>90th percentile of TCH, TG, LDL–CH, VLDL–CH, HDL–CH, AI, TGI) and lower glucose levels (≤10th percentile).Conclusion.Dyslipidemia and hyperglycemia demonstrate synergetic proatherogenic effects in patients with CHD, SEA, MS, and DM-2, as suggested by significant heterogeneous (direct and inverse) associations between lipid profile parameters and fasting blood glucose. The results obtained provide an opportunity for the assessment of risk levels, prognosis, and need for pharmacological prevention and treatment in patients with combined cardiovascular pathology. 


2015 ◽  
Vol 1 (2) ◽  
pp. 235-243
Author(s):  
Most Sumona Akter ◽  
Md Abu Yousuf ◽  
Md Yousuf Ali ◽  
Most Mahfuja Khatun ◽  
Sukumar Saha ◽  
...  

Ground nut is one of the commonly used decorative nutritious relish seed around the world. Ground nut have hypocholesterolamic, hypoglycemic, hypolipidemic, anti-atherosclerotic, immune-modulatory and bacterial counting effects. In Bangladesh, limited research has so far been performed on the action of ground nut in biological system and its comparative efficacy with commercialized drugs that reduce blood cholesterol. The aim of this study was carried on the effects of PUFA on blood total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG) and against artificial inoculation (I/N) Staphylococcus aureus infection of experimental rat by feeding of ground nut. A total of fifteen long Evans rats (Rattus norvegicus) were used for this study. The rats were randomly divided into three equal groups (n=5) and numbered as A, B and C. Group A (control), Group B (50gm ground nut/ day/group), group C (100 gm ground nut/day/group). All groups were supplied with standard broiler pellet and fresh drinking water throughout the experimental period (January to June /2012). The blood samples were collected directly from the heart at the 1st and 60th day for biochemical test (TC, LDL, HDL and TG) and test was performed as per Memorial Diagnostic Centre, Charpara, Mymensingh. Staphylococcus aureus was cultured in nutrient broth and 100 µl of their culture was inoculated into the rats through intranasal route. Among all the treated groups, the rats of group C exhibited the lowest TC value, TG and LDL and reduced blood cholesterol significantly than (control group A) followed by group B. In bacteriological examinations, it was found that the number of bacterial colony lowest in group C in comparison with the group of A and B. From the present experiment, it can be assumed that PUFA has significant effect on blood lipid profile and against bacterial infection.Asian J. Med. Biol. Res. June 2015, 1(2): 235-243


2020 ◽  
pp. 001857872091038
Author(s):  
Roda Plakogiannis ◽  
Joseph J. Saseen ◽  
Abraham Stefanidis

Background: Since 2013 there have been cholesterol guideline changes impacting pharmacists’ clinical practice in managing lipid disorders. For more than a decade, cholesterol management was based on the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol Adult Treatment Panel III guideline, highlighting non-high-density lipoprotein cholesterol (non-HDL-C) as a secondary target in persons with triglycerides ≥200 mg/dL, after low-density lipoprotein cholesterol goal attainment. The 2013 American College of Cardiology and American Heart Association (ACC/AHA) guideline differed from the traditional management of dyslipidemia, in part no longer emphasizing the utilization of non-HDL-C levels. Objective: To measure pharmacists’ attitudes and behavior regarding utilization of non-HDL-C level calculation before and after the inception of the 2013 ACC/AHA cholesterol guideline. Methods: Pharmacists in the American College of Clinical Pharmacy ambulatory care listserv participated in an electronic survey in November 2013, before the inception of the 2013 ACC/AHA guideline, and again in October 2018. Results: We collected 391 usable responses from participants; 212 responses in 2013 and 179 responses in 2018. The before and after comparison revealed that respondents in 2013 reported significantly higher frequency of calculating non-HDL-C levels (mean = 1.88, SD = 0.80) than respondents in 2018 (mean = 1.66, SD = 0.79) ( P ≤ .001). Also, the frequency that non-HDL-C level calculation alters decisions regarding course of treatment was lower in the 2018 (mean = 3.50, SD = 1.06) in comparison with 2013 (mean = 3.77, SD = 0.88) ( P ≤ .05). Furthermore, pharmacists were more favorable toward the inclusion of non-HDL-C level calculation in 2018 (mean = 3.77, SD = 1.05) than in 2013 (mean = 3.13, SD = 1.33) ( P ≤ .001). Conclusion and Relevance: Clinical pharmacists’ utilization of non-HDL-C levels in the clinical management of patients with hypercholesterolemia has decreased, highlighting the need for further education on the importance of evaluating non-HDL-C levels in the very high-risk atherosclerotic cardiovascular disease population.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Zoe Irwin ◽  
Emeir M. McSorley ◽  
Mary M. Slevin ◽  
Lisa Rowan ◽  
Paul McMillen ◽  
...  

AbstractEvidence from observational studies indicates that seaweed consumption may reduce the risk of non-communicable diseases such as cardiovascular disease, type two diabetes, and obesity. Accumulating evidence from in vitro and animal studies suggest seaweed have antihyperlipidemic, anti-inflammatory and antioxidant properties which may in part be attributed to the high content of soluble dietary fibre in seaweeds. The viscosity of seaweed fibres is suggested to mediate antihyperlipdiemic effects via the alteration of lipid/bile acid absorption kinetics to decrease low-density lipoprotein cholesterol (LDL). Thus, there is a need to evaluate the efficacy of seaweed derived dietary fibre in the management of dyslipidemia. Therefore, the aim of this study was to determine the effect of a fibre rich extract from Palmaria palmata on the lipid profile as well as markers of inflammation and oxidative stress in healthy adults. A total of 60 healthy participants (30 male and 30 female) aged 20 to 58 years, were assigned to consume the Palmaria palmata fibre extract (5g/day), Synergy-1 and the placebo (maltodextrin) for a duration of 4 weeks with a minimum 4 week washout between each treatment in a double blind, randomised crossover study conducted over 5 months. Fasting concentrations of cholesterol, triglycerides and high-density lipoprotein cholesterol (HDL) were analysed and low-density lipoprotein cholesterol (LDL) and LDL: HDL ratio was calculated. C-reactive protein (CRP) and Ferric Reducing Ability of Plasma (FRAP) were analysed as markers of inflammation and oxidative stress, respectively. Supplementation for 4 weeks with Palmaria palmata resulted in favourable changes to lipid profiles with a reduced LDL:HDL ratio; however intention-to-treat univariate ANCOVA identified no significant difference between the treatment groups over time on any of the lipid profile markers. A non-significant increase in CRP and triglyceride concentration along with lower FRAP was also observed with Palmaria palmata supplementation. Evidence from this study suggests that Palmaria palmata may have effects on lipid metabolism and appears to mobilise triglycerides. More research is needed in individuals with dyslipidaemia to fully elucidate these effects.


2020 ◽  
Vol 100 (2) ◽  
pp. 272-281
Author(s):  
Hao Yang Sun ◽  
Hyeok Min Yun ◽  
In Ho Kim

The effects of dietary omega-6 (n-6) to omega-3 (n-3) polyunsaturated fatty acid (PUFA) ratios on growth performance, digestibility, blood lipid profiles, fecal microbial counts, and meat quality in finishing pigs were examined by using linseed and fish oil. A total of 140 crossbred finishing pigs [(Landrace × Yorkshire) × Duroc] were used in a 10 wk trial. Pigs were blocked based on body weight (BW) and sex and randomly allotted to four dietary treatments formulated to have n-6/n-3 ratios of 5/1, 10/1, 15/1, and 17/1 (control). Throughout the experiment, BW, average daily gain, and average daily feed intake were significantly (P < 0.05) increased with a decreased ratio of n-6/n-3 PUFA. Energy digestibility and fecal Lactobacillus count showed a linear (P < 0.05) increase in week 10. The high-density lipoprotein cholesterol and blood triglyceride concentrations increased (P < 0.1) during week 10. However, low-density lipoprotein cholesterol was reduced (P < 0.05) linearly during week 5 and week 10 with a reduction in dietary n-6/n-3 ratio. This study provides a basis for future research on altering n-6/n-3 ratio by using linseed oil and refined fish oil in finishing pigs.


2014 ◽  
Vol 43 (1) ◽  
pp. 21-24 ◽  
Author(s):  
GB Das ◽  
ME Hossain ◽  
MA Akbar

This study was conducted with 180 female Swiss albino mice to examine the effects of supplementing broiler fat in the diets of mice on blood lipid profile. Twenty one days old mice were collected from ICDDRB, Mohakhali, Dhaka. They were randomly distributed in four groups having three replications each. Each replicate group had 15 mice. Results revealed that supplementation of broiler fat in mice diet significantly changed (p<0.05) triglyceride (TG) and low density lipoprotein (LDL) among groups. The control group (T0) had the highest level of cholesterol and LDL. Cholesterol, TG and LDL markedly increased (p<0.05) in all dietary treatment groups, while high density lipoprotein (HDL) significantly (p<0.01) decreased after supplementation of experimental diets. It was concluded that all the dietary treatments in general increased blood cholesterol, TG and LDL in mice fed broiler fat with different oil supplements. However, the soybean and palm oil group was comparatively better than other groups in respect of cholesterol, HDL and LDL at the blood lipid profile of mice. Therefore, it can be concluded that consumption of broiler fat with soybean and palm oil could be less harmful for mice.DOI: http://dx.doi.org/10.3329/bjas.v43i1.19380 Bang. J. Anim. Sci. 2014. 43 (1): 21-24


2017 ◽  
Vol 95 (6) ◽  
pp. 661-666 ◽  
Author(s):  
Enas Mahmoud Moustafa ◽  
Noura Magdy Thabet

This study was designed to evaluate the effect of beta-sitosterol (BS) on the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression role in the activity of paraoxonase (PON-1) enzyme in oxidative stress status of irradiated rats. Animals were exposed to whole body γ-radiation single dose 6 Gy and received BS dose (40 mg·(kg body mass)−1·day−1, orally). In liver tissue, gene expression of PPAR-γ ligand was determined. Oxidative stress marker (malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), PON-1, and arylesterase (ARE)) were assayed in serum and liver tissue. Also, serum lipid profile (cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) was measured. In irradiated animals that received BS, expression of PPAR-γ ligand increase significantly associated with increase in PON-1 and ARE enzyme activities. Also, the activities of SOD, CAT enzymes, and HDL-c levels display elevation. By contrast, significant decrease in MDA content, cholesterol, TG, and LDL-c levels were revealed after BS administration. Our findings in this study provide the evidence that BS has radio-protective effect via regulating the gene expression of PPAR-γ, causing an increase in PON-1 and ARE enzyme activities. This action of BS is due to its free radical scavenging properties, antioxidant effect, lowering of cholesterol, and PPAR-γ agonist properties.


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