Prevention of doxorubicin-induced experimental cardiotoxicity by Nigella sativa in rats.

INTRODUCTION: Doxorubicin (DOX) is an anthracycline cytotoxic chemotherapeutic drug that is commonly used in cancer treatment. A major side effect limiting the clinical use of DOX is cardiotoxicity due to oxidative injury. Nigella sativa (NS) is an annual flowering plant with antioxidant properties. Its seeds contain several bioactive constituents such as saturated and unsaturated fatty acids, thymoquinone, dithymoquinone, thymohydroquinone, and thymol. In this study, we investigated the effect of NS extract on DOX-induced cardiotoxicity. METHODS: The experimental study animals consisted of 28 male Sprague Dawley rats weighing between 300 and 400 g. Four study groups each of seven rats were defined: controls; NS extract; DOX; and DOX+NS. Control and DOX rats received standard food, while each rat in the NS and DOX+NS groups also received 100 mg/kg NS extract orally. At day 28 of follow-up, rats in the DOX groups were administered a single 10 mg/kg intraperitoneal dose of DOX, while rats in the control and NS groups received a single 10 mg/kg dose of physiological saline solution. All animals were monitored for 35 days. On day 35, the rats were decapitated and serum and cardiac tissue samples were obtained. Troponin and NT-proBNP levels were measured in blood sera, while malondialdehyde (MDA), nitric oxide, total antioxidant capacity (TAC), and total oxidative stress (TOS) levels were quantified in sera and tissue samples. Histological alterations that were assessed in cardiac tissue included myocyte disarray, small vessel disease, myocyte hypertrophy, and fibrosis. RESULTS: The DOX group had significantly higher NT-proBNP, TOS, and MDA, with greater histopathological derangement. TAC was significantly elevated in the DOX+NS group, which also exhibited significantly lower troponin, TOS, and MDA, as well as significantly higher TAC compared to the DOX group. Histopathological examination showed that the significant structural derangement observed in DOX rats was markedly and significantly reduced in DOX+NS rats. CONCLUSION: Our results suggest that NS extract may prevent DOX-induced cardiotoxicity and thus represents a promising cardioprotective agent.

Effects of grapeseed extract on doxorubicin-induced cardiotoxicity in rats.

BACKGROUND: Doxorubicin (DX) is used for the treatment of many types of cancer; however, a side effect of this agent is cardiotoxicity, which may lead to cardiomyopathy or cardiac failure. Oxidative stress is thought to play a major role in the development of cardiotoxic effects. Proanthocyanidins found in grapeseed (GS) extract may inhibit chemically induced lipid peroxidation and apoptosis caused by oxidative stress. We aimed to investigate the cardioprotective effects of GS extract against DX-induced cardiotoxicity. METHODS: A total of 28 male Sprague Dawley rats were grouped to receive: (a) standard nutrition (n = 7); (b) standard nutrition with an additional dose of 10 mg/kg DX (n = 7); (c) standard nutrition plus 100 mg/kg/day of GS (n = 7); (d) standard nutrition with 100 mg/kg/day of GS plus a single dose of 10 mg/kg DX. After 35 days the rats were decapitated and blood samples were taken for biochemical testing. Cardiac tissue samples were prepared for microscopy and histopathological evaluation. RESULTS: Rats in the DX group exhibited significant elevations in biomarkers such as troponin and NT-proBNP as well as in oxidative stress markers compared with all other groups. Histopathological examination corroborated these findings by demonstrating significant and severe structural injury in the cardiac tissue of DX rates. Moreover, rats in the DX + GS group had significantly lower cardiac injury than rats in the DX group according to both biochemical (troponin and NT-proBNP) and histopathological analyses. Serum malondialdehyde levels (a marker of oxidative stress) in the DX + GS rats were significantly lower than in the DX rats. CONCLUSION: Our findings suggest that GS may reduce the severity of DX-induced cardiotoxicity and thus has the potential to prevent cardiac injury in this setting.

Comparison of Chronic Hemodialysis Patients under Strict Volume Control with respect to Cardiovascular Disease.

BACKGROUND: The objective of this study was to determine the effects of strict volume control and nondipper situation on cardiovascular disease in chronic hemodialysis patients. METHODS: This study is an observational and cross-sectional study including 62 patients with normotensive chronic hemodialysis using no antihypertensive drugs. A series of measurements including ambulatory blood pressure monitoring, left ventricular mass index by echocardiography, common carotid artery intima-media thickness by ultrasound, and body fluids by bioimpedance analysis were conducted for all subjects. RESULTS: The patients were divided into two groups as dippers and nondippers according to their ambulatory blood pressure monitoring results. Average 48 h systolic, diastolic, and mean arterial blood pressure and nocturnal systolic, diastolic, and mean arterial blood pressure were significantly different between the dipper and nondipper groups (p<0.05). Before and after dialysis, extracellular fluid/intracellular fluid and extracellular fluid/dry body weight ratios were significantly higher in the nondipper group. Left ventricle mass index and interventricular septum thickness were significantly higher in the nondipper group (p<0.05). Left ventricle ejection fraction was significantly lower and common carotid artery intima-media thickness was higher in the nondipper group with a statistical significance (p<0.05). A two-predictor logistic model was fitted to the data to predict the comparability of dippers and nondippers. CONCLUSION: According to logistic regression analysis, the odds ratio for daytime diastolic blood pressure indicates that nondippers are 0.45 times more likely to have high blood pressure than dippers in daytime. But in night time, nondippers are about 2.55 times more likely to have high blood pressure comparing to dippers. An important finding of this study is that nondipping pattern is associated with cardiac hypertrophy and lower left ventricle ejection fraction in dialysis of patients with no hypertension. The results also suggest that applying strict volume control to achieve a normal blood pressure alone is not sufficient to reduce the risk of cardiovascular morbidity and mortality if the patients do not have a dipper status of nocturnal blood pressure.

Focusing on a complete blood cell parameter: mean platelet volume levels may be a predictor of coronary slow flow.

BACKGROUND: The relationship between increased mean platelet volume (MPV) and atherosclerosis is well known. In the present study, MPV in patients with coronary slow flow (CSF) and in cases with normal coronary anatomy (NCA) was investigated and compared with the aim of identifying the relationship between CSF and MPV. PATIENTS AND METHODS: We studied 40 patients previously determined via coronary angiography as having NCA and 40 patients with CSF in the coronary blood stream, as identified by thrombolysis in myocardial infarction square. Thus, a total of 80 patients from the Elazig Education and Research Hospital (Elazig, Turkey) were included in the present study retrospectively and laboratory and anamnesis information was scanned into their files. The relationship between MPV and CSF was studied. RESULTS: MPV levels were observed to be significantly higher in the CSF group compared to the NCA group (10.05±1.3 and 8.6±0.6, p<0.001). In receiver operating characteristics analyses, it was determined that an MPV >9.05 measured in CSF patients at application had a predictive specificity of 77.5% and sensitivity of 77.5% for CSF (area under the curve: 0.825, 95% confidence interval [CI]: 0.726-0.924, p<0.0001). It was found that MPV level was an independent predictor of CSF (ß=-600, p<0.001, 95% CI: -0.383 to -0.176). CONCLUSION: MPV is increased in patients with CSF when compared to patients with NCA. This finding supports the fact that MPV could be a predictor of CSF.

Carotid artery stiffness in Behçet's disease.

OBJECTIVE: Increased carotid arterial stiffness (CAS) is a predictor of subclinical early atherosclerosis as well as carotid intima-media thickness (cIMT). We aimed to determine CAS and cIMT in Behçet's disease (BD). MATERIAL AND METHODS: BD (n=49) and rheumatoid arthritis (RA) (n=64) patients and healthy controls (HC) (n=40) were included in the study. cIMT was measured. CAS indices, including arterial compliance (AC), arterial distensibility (AD), Young's elastic modulus (YEM), Peterson's elastic modulus (Ep), and ß stiffness index (ßSI) were measured based on the diameter-pressure relationship. RESULTS: When compared to the HC group, the mean cIMT was significantly higher in the RA group (p=0.033), but it was not higher in the BD group. The CAS indices, including AD, AC, Ep, and ßSI were not significantly different among the study groups. Moreover, the cIMT and CAS indices were not significantly different between active (n=20) and inactive BD patients, and these indices were not correlated with the scores of disease activity. AD, AC and Ep were significantly lower in the BD patients with a positive pathergy reaction than in those with a negative reaction. CONCLUSION: These results suggest that BD does not directly lead to arterial stiffness or to an increase in cIMT.

QT dispersion and P wave dispersion in patients with fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is a chronic disease characterized by widespread pain. Somatic complaints associated with the cardiovascular system, such as chest pain and palpitations, are frequently seen in FM patients. P and QT dispersions are simple and inexpensive measurements reflecting the regional heterogeneity of atrial and ventricular repolarization, respectively. QT dispersion can cause serious ventricular arrhythmias. The aim of the present study was to evaluate QT dispersion and P wave dispersion in patients with FM. MATERIAL AND METHODS: The study involved 48 FM patients who fulfilled the established criteria and 32 healthy controls (HC). A standard 12-lead electrocardiogram was performed on all participants. QT dispersion was defined as the difference between the longest and the shortest QT intervals. Similarly, the differences between the shortest and longest P waves were defined as P wave dispersion. RESULTS: The QT dispersion and corrected QT dispersion were shorter in the FM group compared with the HC group (p<0.001 for both). In terms of the P wave dispersion value, there was no significant difference between the FM and HC groups (p=0.088). CONCLUSION: Longer QT and P wave dispersions are not problems in patients with FM. Therefore, it may be concluded that fibromyalgia does not include an increased risk of atrial and/or ventricular arrhythmias.

The efficacy of CT for detection of right ventricular dysfunction in acute pulmonary embolism, and comparison with cardiac biomarkers.

PURPOSE: The purpose of this study was to evaluate results from computed tomography pulmonary angiography (CTPA) indicative of right ventricular dysfunction (RVD), and to assess the relationship of these results with cardiac biomarkers and mortality among patients with acute PE. MATERIALS AND METHODS: This retrospective study involved 118 patients with acute PE proved by CTPA. CTPA variables were analyzed and compared with cardiac biomarkers and echocardiography (ECHO) findings. RESULTS: Compared with ECHO, the sensitivity, specificity, positive predictive value, and negative predictive value of CTPA for detection of RVD were 85.7, 91.7, 93.7, and 81.5 %, respectively. ROC curve analysis for prediction of RVD resulted in areas under the curve of 0.925 for RV dimension (95 % CI 0.879-0.971, p < 0.001) and 0.913 for main pulmonary artery (MPA) diameter (95 % CI 0.863-0.963, p < 0.001). The optimum cut-off values for prediction of RVD were 37.5 mm for RV dimension and 29.1 mm for MPA diameter. These values were also statistically significantly greater for non-survivors than for survivors (p = 0.001, p < 0.001, respectively) and significantly associated with cardiac biomarkers. CONCLUSION: It was found that CTPA findings were significantly associated with the presence of RVD in ECHO, cardiac biomarkers, and mortality of patients with acute PE.

The rs3768777-G allele of ITGAV gene is associated with rheumatoid arthritis.

Integrin αvß3 (vitronectin receptor) plays a prominent role in angiogenesis, a key pathogenic feature of rheumatoid arthritis (RA). Moreover, integrin αV (ITGAV) subunit gene has been associated with a susceptibility to RA. The aim of the present study was to detect the potential association between ITGAV gene polymorphisms and a susceptibility to RA in a Turkish cohort. DNA samples were harvested from 160 patients with RA and 144 healthy controls (HC). Three single-nucleotide polymorphisms of ITGAV gene (rs3738919, rs3768777, and rs10174098) were genotyped using real-time PCR. Serum vitronectin levels were analyzed in 30 RA patients, 28 Behçet's disease (BD) patients, and 30 HC subjects. There was no significant difference between the RA and HC groups in terms of the genotypic and allelic distributions of rs3738919 and rs10174098 polymorphisms. However, the prevalence of rs3768777-G allele was higher in the RA group than in the HC group (OR 2.3, 95 % CI 1.6-3.2, p < 0.0001). Moreover, there was a significant association between RA and the genotypic distribution of rs3768777 (GG + AG vs. AA: OR 2.1, 95 % CI 1.3-3.4; GG vs. AG + AA: OR 4.1, 95 % CI 2.1-7.8). Serum vitronectin levels were lower in the RA and BD groups than in the HC group (p ANOVA = 0.002). The rs3738919 and rs10174098 polymorphisms of the ITGAV gene seem not to be associated with susceptibility to RA in Turkish patients. However, rs3768777 increases the risk of RA in this group. These results suggest that the ITGAV gene may be a candidate gene for the etiopathogenesis of RA.

The relationship between platelet collagen receptor glycoprotein VI and no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction.

OBJECTIVES: The purpose of this study was to determine whether admission soluble glycoprotein VI (sGP-VI) level is associated with no-reflow phenomenon (NRP) after primary percutaneous coronary intervention (P-PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 178 consecutive patients admitted to our hospital for a first STEMI and undergoing P-PCI within 12 hours of onset of symptoms were enrolled. The patients were divided into 2 groups (NRP group and reflow group). Admission sGP-VI plasma levels were measured by enzyme-linked immunosorbent assay. RESULTS: Of the 178 patients who underwent P-PCI, 41 patients (23%) developed NRP. The patients in the reflow group had higher levels of sGP-VI compared with the patients in the NRP group (38.5 ± 21.0 vs 21.9 ± 11.9 ng/mL, P < 0.001). The sensitivity and specificity values of the sGP-VI levels were 90% and 49%, respectively (cutoff value was ≤ 25). In the multivariate logistic regression analyses, sGP-VI levels of 25 ng/mL or lower, higher peak troponin T levels and body mass index value, amount of opaque of greater than 250 mL, and lesion length of greater than 13.5 mm were independent predictors of angiographic NRP. CONCLUSIONS: Lower admission sGP-VI levels are associated with NRP in patients with STEMI undergoing P-PCI. This outcome may open new therapeutic facility in the setting of P-PCI.

Serum salusin-α levels in systemic lupus erythematosus and systemic sclerosis.

OBJECTIVE: Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), chronic inflammatory diseases, demonstrate an increased incidence of cardiovascular manifestations and subclinical atherosclerotic disease. Salusin-α is a novel bioactive peptide that suppresses the formation of macrophage foam cells, and its serum level is significantly lower in patients with angiographically proven coronary artery disease. The aims of the study were to assess serum salusin-α level and its potential association with the predictors of atherosclerosis in SLE and SSc. MATERIAL AND METHODS: The study included 20 SLE and 22 SSc patients and 23 healthy controls (HC). All of the participants were female. Tumour necrosis factor-α (TNF-α), IL-6 and salusin-α levels, homeostasis model assessment for insulin resistance (HOMA-IR) index and common carotid intima-media thickness (IMT) were determined. RESULTS: Salusin-α levels were lower and the IMTs were higher in the SLE and SSc groups than in the HC group. The salusin-α level was correlated with neither the disease activity scores nor cytokine levels and IMT in the SLE and SSc groups, although it was correlated with triglyceride level in the SLE group (r=-0.564, p=0.012), and with HOMA-IR index in the HC group (r=0.485, p=0.019). CONCLUSION: The present preliminary study may support the idea that SSc leads to subclinical atherosclerosis, as in SLE. Moreover, it can be concluded that the decreased salusin-α levels in SLE and SSc may contribute to subclinical atherosclerosis. However, further studies with larger sample size are needed to demonstrate this contribution in SLE and SSc.