Coadministration of Atorvastatin and Amiodarone Increases the Risk of Pulmonary Fibrosis in Rats.

OBJECTIVE: The purpose of this study was to evaluate the effect of atorvastatin administration on amiodarone-induced pulmonary fibrosis in rats. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly divided into 4 groups. The control group (CTL) received distilled water (0.3 ml intratracheally on days 0 and 2 and 0.5 ml orally from day 0 for 3 weeks). The atorvastatin group (AT), in addition to intratracheal distilled water, received 1 mg/kg of atorvastatin orally from day 0 for 3 weeks. The amiodarone group (AMI) received 2 intratracheal instillations of amiodarone (6.25 mg/kg in 0.3 ml of water) on days 0 and 2 and 0.5 ml of distilled water (like the CTL). The amiodarone plus atorvastatin group (AMI + AT) received both these drugs (same doses and methods as for the AMI and AT). After 28 days, the rate of lung fibrosis was estimated according to pathological criteria of lung sections and measurements of hydroxyproline in pieces of left lung tissue. RESULTS: The lung hydroxyproline content was higher in the treated groups (CTL: 0.35 ± 0.017, AT: 0.38 ± 0.012, AMI: 0.375 ± 0.018 and AMI + AT: 0.38 ± 0.012 unit/mg protein), but did not reach significance when compared with the CTL (p = 0.56). Amiodarone administration significantly increased the score of pulmonary fibrosis (0.5) in comparison with the AT (0.125) and CTL (0) (p < 0.5). The combination of amiodarone and atorvastatin exacerbated the pulmonary fibrosis (1.5; p < 0.01) compared to the AMI (0.5; p < 0.001), AT (0.125) and CTL (0). CONCLUSION: In this study, the concomitant administration of amiodarone and atorvastatin increased pulmonary fibrosis in rats.

The effect of vitamin D administration on serum leptin and adiponectin levels in end-stage renal disease patients on hemodialysis with vitamin D deficiency: A placebo-controlled double-blind clinical trial.

BACKGROUND: The prevalence of vitamin D deficiency is higher in end-stage renal disease (ESRD) patients compared to healthy populations. This deficiency could lead to several complications with different mechanisms and might result in reduced survival in patients. Leptin and adiponectin are messenger proteins with endocrine secretion from adipocytes and various effects in cellular mechanisms. The goal of this study was to find the effect of vitamin D administration on serum levels of leptin and adiponectin in ESRD patients. MATERIALS AND METHODS: This double-blind randomized placebo-controlled clinical trial was carried out on 64 ESRD patients on hemodialysis in the Amin and Noor hospitals of Isfahan, Iran. Patients were categorized into two groups, on control and intervention; serum levels of vitamin D, leptin, and adiponectin were measured in both groups before and after the study. The intervention group was treated with vitamin D pearls, while the control group received placebo in the same manner. RESULTS: The mean [standard deviation (SD)] ages of the patients were 62 (21) years and 60 (19) years in the control and treated groups, respectively. CONCLUSION: The change in serum level of vitamin D was statistically significant in the treatment group but not in the control group. The serum level of leptin was reduced in the treatment group, while the serum level of adiponectin increased significantly, but none of these changes were statistically significant in the control group. This study showed that vitamin D administration is associated with an increase in adiponectin and a decrease in leptin level in ESRD patients.

Diabetes mellitus and renal failure: Prevention and management.

Nowadays, diabetes mellitus (DM) and hypertension are considered as the most common causes of end-stage renal disease (ESRD). In this paper, other than presenting the role of DM in ESRD, glucose metabolism and the management of hyperglycemia in these patients are reviewed. Although in several large studies there was no significant relationship found between tight glycemic control and the survival of ESRD patients, it is recommended that glycemic control be considered as the main therapeutic goal in the treatment of these patients to prevent damage to other organs. Glycemic control is perfect when fasting blood sugar is less than 140 mg/dL, 1-h postprandial blood glucose is less than 200 mg/dL, and glycosylated hemoglobin (HbA1c) is 6-7 in patients with type 1 diabetes and 7-8 in patients with type 2 diabetes. Administration of metformin should be avoided in chronic renal failure (CRF) because of lactic acidosis, the potentially fatal complication of metformin, but glipizide and repaglinide seem to be good choices.

Antioxidant plants and diabetes mellitus.

The incidence of diabetes mellitus (DM) is increasing rapidly and it is expected to increase by 2030. Other than currently available therapeutic options, there are a lot of herbal medicines, which have been recommended for its treatment. Herbal medicines have long been used for the treatment of DM because of the advantage usually having no or less side-effects. Most of these plants have antioxidant activities and hence, prevent or treat hard curable diseases, other than having the property of combating the toxicity of toxic or other drugs. In this review other than presenting new findings of DM, the plants, which are used and have been evaluated scientifically for the treatment of DM are introduced.

Ameliorative effect of melatonin against contrast media induced renal tubular cell injury.

BACKGROUND AND OBJECTIVE: Reactive oxygen species (ROS) is a mediator of renal damage. Melatonin is a potent-free radical scavenger. Our objective was to test whether melatonin would protect against the nephrotoxicity of contrast media. METHODS: In an experimental study 40 adult male Wistar rats were randomly divided into four equal groups including: 1) Control group (No drug), 2) Contrast media group (10 ml/kg iodixanol i.v. single dose), 3) Contrast media and melatonin (first 10 ml/kg iodixanol then 10 ml/kg/day melatonin by i.p. injection on days 3, 4 and 5) and 4) Contrast media and melatonin pretreatment group (melatonin 10 ml/ kg/day by i.p. injection on 1, 2 and 3 days, then 10 ml/kg iodixanol by i.v. injection on third day. The blood creatinine and BUN as well as the histological changes were evaluated for severity of renal injury (degeneration, vacuolization of tubular renal cells, dilatation of tubular lumen and presence of debris in the lumens), by scoring from one to four. RESULTS: Contrast media significantly increased the creatinine and BUN and renal injury (p<0.05). Melatonin prevented and reversed the injury induced by contrast media (P<0.05). Pretreatment with melatonin reduced the renal injury induced by contrast media (P<0.05). CONCLUSION: Melatonin is an effective drug to prevent contrast-induced renal injury. Therefore its usage (especially pretreatment) might be beneficial in patients who are planning to use contrast media agents.

Metformin: Current knowledge.

Diabetes mellitus is a group of metabolic disorders in which the blood glucose is higher than normal levels, due to insufficiency of insulin release or improper response of cells to insulin, resulting in high blood pressure. The resultant hyperglycemia produces sever complications. Metformin drug has been shown to prevent diabetes in people who are at high risk and decrease most of the diabetic complications. Recent reports on metformin, not only indicate some implications such as renoprotective properties have been suggested for metformin, but some reports indicate its adverse effects as well that are negligible when its benefits are brought into account. We aimed here to review the new implications of metformin and discuss about the concerns in the use of metformin, referring to the recently published papers.

A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy.

BACKGROUND: The renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of this systematic review is to assess the association of the RAAS genes with diabetes mellitus (DM) and its complications of retinopathy, neuropathy and cardiovascular disease (CVD). MATERIALS AND METHODS: The relevant English-language studies were identified using the key words of DM, type 1 diabetes mellitus (T1DM), T2DM, renin angiotensin aldosterone polymorphisms or genotypes and RAAS from the search engines of MEDLINE/PubMed, and Scopus from January 1, 1995 to July 30, 2014. Inclusion criteria for selecting relevant studies were reporting the role of RAAS gene variants in the pathogenesis of T1DM or T2DM, diabetic retinopathy (DR), diabetic neuropathy and cardiovascular complication of DM. RESULTS: The reviewers identified 204 studies of which 73 were eligible for inclusion in the present systematic review. The review indicates the angiotensinogen (AGT) M235T polymorphism might not affect the risk of DM. The role of angiotensin converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor gene (AT1R) A1166C polymorphisms in the pathogenesis of DM could not be established. Studies indicate the absence of an association between three polymorphisms of AGT M235T, ACE I/D and AT1R A1166C and DR in DM patients. A protective role for ACE II genotype against diabetic peripheral neuropathy has been suggested. Also, the ACE I/D polymorphism might be associated with the risk of CVD in DM patients. CONCLUSION: More studies with adequate sample size that investigate the influence of all RAAS gene variants together on the risk of DM and its complications are necessary to provide a more clear picture of the RAAS genes polymorphisms involvement in the pathogenesis of DM and its complications.

Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants.

Hypertension is a major risk factor for myocardial infarction, heart failure, stroke, peripheral arterial disease, and aortic aneurysm, and is a cause of chronic kidney disease. Hypertension is often associated with metabolic abnormalities such as diabetes and dyslipidemia, and the rate of these diseases is increasing nowadays. Recently it has been hypothesized that oxidative stress is a key player in the pathogenesis of hypertension. A reduction in superoxide dismutase and glutathione peroxidase activity has been observed in newly diagnosed and untreated hypertensive subjects, which are inversely correlated with blood pressure. Hydrogen peroxide production is also higher in hypertensive subjects. Furthermore, hypertensive patients have higher lipid hydroperoxide production. Oxidative stress is also markedly increased in hypertensive patients with renovascular disease. If oxidative stress is indeed a cause of hypertension, then, antioxidants should have beneficial effects on hypertension control and reduction of oxidative damage should result in a reduction in blood pressure. Although dietary antioxidants may have beneficial effects on hypertension and cardiovascular risk factors, however, antioxidant supplementation has not been shown consistently to be effective and improvement is not usually seen in blood pressure after treatment with single or combination antioxidant therapy in subjects thought to be at high risk of cardiovascular disease. This matter is the main focus of this paper. A list of medicinal plants that have been reported to be effective in hypertension is also presented.

Comment on: A model for prediction of cisplatin induced nephrotoxicity by kidney weight in experimental rats.

Cisplatin (cis-diamminedichloroplatinum II), as one of the most applicable and potent anticancer medication, is used in the treatment of a various pediatric and adult malignancies. However, it gives side-effects such as renal toxicity which is dose-dependent, and thus limited its usage. Treatment with cisplatin induces the inflammatory mechanisms, which leads to a reduction in the antioxidant levels, leading to a failure of the antioxidant protection against free-radical damage generated by antitumor drugs. The oxidative stress, induced by cisplatin in the kidney was partially inhibited by antioxidant therapy using selenium, glutathione, flavonoids, and superoxide dismutase.

Association of serum uric acid with proteinuria in type 2 diabetic patients.

BACKGROUND: Various findings suggest that uric acid is an inflammatory factor and may have a role in endothelial dysfunction and act as a mediator of diabetic nephropathy. The objective of this study was to evaluate the relationships between serum uric acid level and level of proteinuria in type 2 diabetic (T2D) patients. MATERIALS AND METHODS: A cross-sectional analytical study was conducted in 60 patients with T2D without a history of gout. None was treated with allopurinol. Venous blood samples were obtained in fasting state for determinations of serum creatinine, uric acid, and hemoglobin A1c (HbA1c) (reference range 3.8-5.5%); 24-h urine proteinuria was also measured. RESULTS: Mean age of the patients was 57 ± 8.3 years. Mean ± standard error (SE) of serum creatinine was 0.98 ± 0.028 mg/dL, mean ± SE of serum uric acid was 4.5 ± 0.15 mg/dL, and mean ± SE of proteinuria was 388 ± 28.7 mg/day (median = 303.5 mg/day). There was no significant difference in serum uric acid, HbA1c, and creatinine level between males and females (P > 0.05). There was a significant positive association between body mass index (BMI) and serum uric acid levels (r = 0.428, P = 0.001). After adjustment for weight, a significant positive association of serum uric acid with level of proteinuria was seen (r = 0.47, P < 0.001). CONCLUSION: Serum uric acid had a significant positive association with diabetic nephropathy. It might be hypothesized that serum uric acid plays a role in diabetic nephropathy in T2D.

A model for prediction of cisplatin induced nephrotoxicity by kidney weight in experimental rats.

BACKGROUND: Cisplatin (cis-diamminedichloroplatinum II; CP) is used widely as an antitumor drug in clinics, but is accompanied with renal toxicity. Cisplatin induced nephrotoxicity consists of change in kidney weight, histological changes in kidney and increase in serum creatinine (Cr) and blood urea nitrogen (BUN). This study was designed to find out a model for prediction of cisplatin induced nephrotoxicity. MATERIALS AND METHODS: Pathological damage score, kidney weight, BUN, and Cr of 227 rats that were involved in different projects were determined. A total of 187 rats were treated with 7 mg/kg cisplatin and sacrificed 1 week later. RESULTS: There was a good significant correlation between normalized kidney weight and logarithmic scale of BUN and Cr. Relationship between BUN, Cr or normalized kidney weight and pathology damage score was significant. CONCLUSION: Normalized kidney weight and pathology damage score is a good predictor of renal function in cisplatin induced nephrotoxicity in experimental rats.

Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model.

BACKGROUND: Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well-documented; but its nephron-protective effect against CP-induced nephrotoxicity is not completely understood. MATERIALS AND METHODS: Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1-3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies. RESULTS: The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP-treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen-treated groups (Groups 1-3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r (2) = 0.63, P < 0.01). CONCLUSION: Estrogen is not nephron-protective against CP-induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen-induced oxidative stress in the kidney, which may promote the nephrotoxicity.

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.

The Association Between Arsenic Levels and Oxidative Stress in Myocardial Infarction: A Case-Control Study.

Cardiovascular diseases (CVDs) are known as the first causes of death throughout the world, and mainly myocardial infarction (MI), lead to 7.4 million deaths annually. Atherosclerosis is the major underlying cause of most CVDs. However, exposure to heavy metals, among other factors, deserves further attention as a risk factor for CVDs. This study was designed to evaluate the levels of arsenic (Ars) in myocardial infarction (MI) patients and healthy individuals as well as assess the association between the incidence of MI and Ars, total antioxidant capacity (TAC), and oxidative stress. This case-control study was conducted among patients with MI (n = 164) and normal individuals (n = 61) at Shafa Hospital in Kerman, Iran. Patients were classified into two groups, including coronary artery blocks above 50% (CAB > 50%, n = 83) and coronary artery blocks less than 50% (CAB < 50%, n = 83) based on their angiography findings. The demographic characteristics, clinical history, biochemical parameters, and serum Ars and TAC levels were evaluated. In the present study, both CAB groups had significantly reduced levels of TAC compared with the control. Furthermore, TAC was lower in the CAB > %50 group compared to the CAB < %50 group. Ars levels were significantly higher in both CAB groups compared with the control. There was a significant positive relationship between CAB and Ars, BG, HbA1c, urea, creatinine, TG, TC, and LDL-c, as well as a negative relationship between HDL-c and TAC. Moreover, TAC levels showed a significant inverse correlation with Ars, HbA1c, and creatinine, and a positive correlation with HDL-c. As risk factors, Ars, hs-CRP, TG, TC, and LDL-c enhance the severity of the disease, and HDL-c and TAC decrease the disease severity. Moreover, ROC curve analysis revealed that the highest AUC for the CAB > %50 (AUC = 78.29), and cytotoxic levels for both CAB groups (Ars ≥ 0.105 ppm), and no significant differences were found between the two groups. Our findings suggest that Ars at ≥ 0.105 ppm is able to increase the risk of MI through the increased OS and decreased TAC.

The role of angiotensin II receptor 1 (AT1) blockade in cisplatin-induced nephrotoxicity in rats: gender-related differences.

It is documented that chronic renal diseases are gender related. The protective role of angiotensin II receptor 1 (AT1) blocker losartan against cisplatin (CP)-induced nephrotoxicity was reported in males, but the role of gender is not well known. Six groups of Wistar rats were studied. Rats were divided into two groups of males and females to receive losartan for 9 days plus a single dose of CP (7 mg/kg) at day 3. Two positive control groups of males and females received the same regimen, except that they received saline instead of losartan. The negative control groups received saline instead of CP at day 3 and also saline instead of losartan. The blood samples were obtained, and the kidneys underwent histopathological investigations. All the CP-treated animals lost weight, but losartan promoted weight loss in females (p < 0.05). Coadministration of losartan and CP in females, but not in males, significantly increased the serum levels of blood urea nitrogen and creatinine when compared with the negative and positive control groups (p < 0.05). No significant differences were observed in serum levels of total proteins, magnesium, and nitrite between the groups. Administration of CP increased the kidney tissue damage score (KTDS) and normalized kidney weight (p < 0.05). However, in the presence of AT1 blockade, the KTDS (nonsignificantly) and normalized kidney weight (significantly, p < 0.05) increased in the CP-treated females. Such an observation was not seen in males. Losartan may prevent CP-induced nephrotoxicity in males, but it promotes the CP-induced damage in females, which may be related to the renin-angiotensin system receptors in the kidneys.

Ameliorative effects of metformin on renal histologic and biochemical alterations of gentamicin-induced renal toxicity in Wistar rats.

BACKGROUND: The aim of this study was to test the potential properties of metformin (MF) to protect the kidney from gentamicin (GM)-induced renal toxicity. MATERIALS AND METHODS: In this preclinical study, 50 male Wistar rats were randomly divided into five groups of 10 rats in each. In the first group (group I), they were kept in the same condition as others without receiving drugs for 10 days. In group II, the rats were injected intraperitoneally with 100 mg/kg/day of GM for 10 consecutive days. Group III rats received 100 mg/kg/day MF orally for 10 days. In group IV, the rats received GM (100 mg/kg; intraperitoneally) for 10 days and 100 mg/kg/day MF orally for the next 10 days. In the last group (group V), the rats received a combination of GM 100 mg/kg/day intraperitoneally and MF 100 mg/kg/day orally for 10 days simultaneously. Serum blood urea nitrogen (BUN) and creatinine (Cr) values were measured and renal tissues of the animals were processed for light microscope examination. RESULTS: The levels of BUN in groups II, IV, and V, and also the serum level of Cr in groups II and V were increased significantly after the experiment. Furthermore, post-treatment with MF or co-treatment with MF could prevent the elevation of serum BUN and Cr induced by GM and also attenuates the damage score (P < 0.05). CONCLUSIONS: MF may prevent or ameliorate GM-induced acute renal failure, and therefore it might be beneficial in patients under treatment with this medicine.

Moderate Endurance Training and MitoQ Improve Cardiovascular Function, Oxidative Stress, and Inflammation in Hypertensive Individuals: The Role of miR-21 and miR-222: A Randomized, Double-Blind, Clinical Trial.

OBJECTIVE: Hypertension (HTN) is among the leading causes of myocardial infarction, stroke, and kidney disease. The MitoQ supplement is a mitochondrial-targeted antioxidant that attenuates the generation of reactive oxygen species (ROS). miRNAs play an essential role in the pathophysiology of HTN. Regular aerobic exercise is recommended to decrease the risk of cardiovascular disease. We aimed to evaluate the effects of MitoQ supplementation and moderate endurance training (ET), alone and in combination, on cardiac function, blood pressure, the circulatory levels of miRNA-21 and miRNA-222, and oxidative status in individuals with HTN. MATERIALS AND METHODS: In a double-blind, randomized clinical trial (except for ET group), 52 male hypertensive subjects (40-55 years old) were randomly divided into four groups (n=13): Placebo, MitoQ (20 mg/day, oral), ET (Cycle ergometer, moderate intensity, 40-60% VO2 peak, three sessions/week for six weeks), and MitoQ+ET. Cardiac echocardiography indices, serum oxidative and inflammation status, and miRNAs 21 and 222 were assessed before and after interventions. RESULTS: Left ventricular mass [effect size (ES): -6.3, 95% confidence interval (CI): -11.2 to -1.4] and end-systolic/ diastolic diameters significantly improved in the intervention groups (ES: -0.05, 95% CI: -0.11 to 0.00 and -0.09, 95% CI: -0.16 to -0.02). Total serum antioxidant capacity (TAC) increased (ES: 36.0, 95% CI: 26.1 to 45.8), and malondialdehyde (MDA) (ES: -0.43, 95% CI: -0.53 to -0.32), IL-6 (ES: -1.6, 95% CI: -1.98 to -1.25), miR-21 (ES: -0.48, 95% CI: -0.61 to -0.35), and miR-222 (ES: -0.31, 95% CI: -0.44 to -0.18) significantly decreased in response to ET, MitoQ, and their combination. CONCLUSION: MitoQ and ET, individually and more pronouncedly in combination, can improve cardiovascular health in people with high blood pressure (BP) by reducing inflammation and increasing antioxidant defense, in association with reduction in circulatory miR-21 and miR-222 levels (registration number: IRCT20190228042870N1).

Prevalence and incidence of pre-hypertension and hypertension (awareness/control) in Iran: findings from Kerman coronary artery diseases risk factors study 2 (KERCADRS).

Hypertension (HTN) is an important cause of cardiovascular-related morbidity and mortality. The present study was conducted to investigate the prevalence and incidence rate of pre-HTN, diagnosed and undiagnosed HTN, as well as its control and associated factors in adult population in southeast Iran. In a randomized household survey, 9987 participants aged 15-80 years were recruited into the study. HTN was confirmed through examination or using antihypertensive drug(s). Pre-HTN and HTN were defined as 120-139/80-89 and ≥140/90 mmHg for systolic and diastolic BP, respectively. The prevalence of pre-HTN was 28.5%. The prevalence of HTN was 19.2% (13.9% diagnosed and 5.3% undiagnosed). HTN increased with age (from 4% in 15-24 to 67.8% in 75-80 years). Men had higher pre-HTN (35.6% vs. 23.4%) and undiagnosed HTN (7.5% vs. 3.8%) than women. Of those diagnosed, 46.5% had uncontrolled BP, in which, women had better conditions than men (45.6% vs. 47.4%). Obesity, positive family history of HTN, anxiety, and low physical activity were the most significant predictors of HTN. The prevalence of pre-HTN decreased but there was no change in the prevalence of HTN during the last 5 years. The 5-year incidence rate/100 person-years of pre-HTN and HTN was 6.6 and 3.7, respectively. Although there are some promising signs of reducing pre-HTN and slowing HTN rise, currently, almost one-fifth of the adult population suffers from HTN. Given the poor BP control in patients with diagnosed HTN, especially in men, alarms that more effective interventions and strategies are needed to reduce deleterious consequences of HTN.

Effect of Combined Endurance Training and MitoQ on Cardiac Function and Serum Level of Antioxidants, NO, miR-126, and miR-27a in Hypertensive Individuals.

OBJECTIVES: Hypertension (HTN) is one of the most important risk factors for cardiovascular diseases. Despite advances in treatment and control of HTN, the prevalence of HTN is still increasing. MitoQ is a supplement that acts on mitochondria and attenuates reactive oxygen species (ROS), which plays an important role in cardiovascular health. miRNAs play an important role in the pathophysiology of HTN. We evaluated the effects of MitoQ supplementation and endurance training (ET), alone and in combination, on functional indices of the heart and serum levels of miR-126, miR-27a, antioxidants, and NO, in patients with HTN. METHODS: In a double-blind randomized clinical trial, 52 male participants (age 40-55 years) were randomly divided into four groups (n = 13) of placebo, MitoQ (20 mg/day, oral), ET (cycle ergometer, moderate intensity, 40-60% VO2 peak, heart rate 120-140 b/min, 45 min a day, three days/week for six weeks), and MitoQ+ET. Cardiac function indices were assessed by echocardiography before and after interventions. RESULTS: Systolic blood pressure (SBP) significantly decreased in all intervention groups (P < 0.001) while DBP (P < 0.01) and LV hypertrophy (P < 0.05) were significantly decreased only in the MitoQ+ET group. Serum levels of SOD, GPx, and NO and the level of miR-126 significantly increased in all treatment groups, while miR-27a reduced in the ET (P < 0.05) and MitoQ+ET (P < 0.01) groups. CONCLUSIONS: Compared to MitoQ and ET alone, their combination has more prominent improving effects on cardiac health and amelioration of BP in the patients with HTN. These effects are through miR-126 and miR-27a modulation and ameliorating mitochondrial ROS production.