Çağdaş Akgüllü

The Effect of L-Carnitine on Oxidative Stress Responses of Experimental Contrast-Induced Nephropathy in Rats

ABSTRACT This study was conducted to investigate the prophylactic effects of carnitine against contrast-induced nephropathy (CIN) and its relation to oxidant/antioxidant status in kidney, liver, heart, spleen and lung tissues in a CIN rat model. Twenty-eight adult male Wistar rats were divided into 4 groups, the control, contrast media (CM), carnitine and contrast media+carnitine (CM+carnitine) groups. Animals were placed in individual metabolism cages, and on the 2nd day, rats were deprived of water for 24 hr. On the 3rd day, contrast media were administered to groups CM and CM+carnitine. L-carnitine was administered on days 2, 3 and 4. Histopathological changes were evaluated in the right kidney after euthanization. Superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) and malondialdehyde (MDA) levels were measured in renal, liver, heart, spleen and lung tissues. The SOD activities in the renal (P<0.05), liver (P<0.001) and spleen (P<0.05) tissues were increased in the carnitine group. The CAT activities in the spleen tissue were decreased (P<0.01) only in the CM group. Renal (P<0.05), liver (P<0.001), spleen (P<0.001) and lung tissue (P<0.01) GSH levels were found to be higher in the carnitine group. In renal, liver and lung tissues, the MDA levels increased in the CM group (P<0.001). The histopathological findings showed that L-carnitine may have a preventative effect in alleviating the negative effects of CIN. Similar to this, L-carnitine may play a major role in the stability of the antioxidant status in the kidney, liver, spleen and lung of the CIN rat model.

Predictors of early death in patients with acute pulmonary embolism

AIM We aimed to determine the predictors of early death in the course of acute pulmonary embolism (APE). MATERIALS AND METHODS We included 206 patients who had been admitted to our hospital between January 2011 and April 2013 with the diagnosis of APE. We derived a new model including corrected QT interval dispersion (QTcd) and P wave dispersion (Pd), echocardiographic findings, laboratory markers, and blood cell count indices to predict early death in patients with APE. RESULTS Thirty patients (14.5%) died; 176 patients (85.5%) lived after diagnosis of APE. Logistic regression (LR) analysis found that troponin I (odds ratio [OR], 1.084 [95% confidence interval {CI}, 1.009-1.165]), creatinine (OR, 4.153 [95% CI, 1.375-12.541]), mean platelet volume (OR, 1.991 [95% CI, 1.230-3.223]), neutrophil to lymphocyte ratio (NLR) (OR, 1.079 [95% CI, 1.005-1.160]), QTcd (OR, 1.084 [95% CI, 1.043-1.127]), Pd (OR, 1.049 [95% CI, 1.004-1.096]) were associated with early death in APE. New LR model (area under the curve [AUC], 0.970) performed better than the simplified pulmonary embolism severity index (sPESI) score (AUC, 0.859) in predicting early death in APE (P=.021). The predictivity of the sPESI score significantly improved after its single combination with creatinine, QTcd, or troponin I. When the combined model was constructed together with these 6 independent variables and sPESI score, stepwise LR model automatically excluded Pd and NLR, and the AUC from the rest of the combined model was 0.976, which is significantly different from the AUC of sPESI (0.859) (P=.0031). CONCLUSIONS Creatinine, troponin I, and QTcd significantly improves sPESI score. A new model with troponin I, creatinine, mean platelet volume, NLR, QTcd, and Pd seems to have greater prognostic power than the sPESI scoring system.

Nebivolol to attenuate the effects of hyper-homocysteinaemia in rats

OBJECTIVE This study investigated the prophylactic effect of nebivolol against hyper-homocysteinaemia (hHcy) induced oxidative stress in brain, heart, liver and kidney tissues and histomorphometric changes in the thoracic aorta. METHODS Twenty-four adult male Wistar rats were divided into a control, nebivolol, hHcy and nebivolol+hHcy group. hHcy was induced by oral administration of L-methionine (1 g/kg/day) for 28 days. 10 mg/kg/day nebivolol was administered orally for 28 days. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) and superoxide dismutase (SOD) activities in the tissues were determined. The total cross-sectional area (TCSA), luminal cross-sectional area (LCSA) and intima-media thickness (IMT) were measured in the thoracic aorta. RESULTS Homocysteine (Hcy) levels were lower in the nebivolol+hHcy group than in the hHcy group. Nebivolol treatment significantly decreased high MDA levels in the brain, heart and liver tissues. The level of GSH was higher in the brain, heart and kidney tissues of the nebivolol+hHcy group (P<0.001). The activity of CAT increased only in the kidney tissue of the nebivolol+hHcy group (P<0.01), and the activity of SOD was significantly increased in all the tissues in this group. Increased TCSA and IMT in the nebivolol+hHcy group were significantly decreased after nebivolol administration. The LCSA was significantly higher in the hHcy group than the control group, probably due to outward vascular remodelling. CONCLUSION Nebivolol treatment may be useful in different clinical scenarios where hHcy affects physiopathological pathways.

The first histopathological evidence of trimetazidine for the prevention of contrast-induced nephropathy.

Abstract Aim: We aimed to investigate the prophylactic effects of trimetazidine (TMZ) against contrast-induced nephropathy (CIN) in rat kidneys. Methods and results: 28 Wistar rats were divided into 4 groups of 7 rats each (control (C), contrast media (CM) TMZ, trimetazidin + contrast media groups (TMZ + CM). The administration of TMZ solution was done on d2, d3 and d4. Fifth day, contrast media was administered at a single dose. On d6 scarification was performed. The oxidant/antioxidant parameters were measured and histopathological scores were performed in kidney tissues. Most of the histopathological scores were significantly higher in the CM group as compared to other groups. Moreover, the scores of the TMZ + CM and C groups were not statistically different. CM group, had significantly higher levels of MDA compared to the C and CM + TMZ groups (562.82 ± 38.15 vs. 419.15 ± 49.01 and 507.34 ± 14.16 01 nmol/mg protein respectively) (p < 0.001). CM group had significantly lower levels of SOD as compared to C, CM + TMZ and TMZ groups (p < 0.05). Conclusion: To the best of our knowledge, this study for the first time, histopathologically demonstrated the effectiveness of TMZ for the prevention of CIN.

Evaluation of left ventricular systolic and diastolic functions in patients with coronary slow flow phenomenon

OBJECTIVES In this study, systolic and diastolic function parameters were measured with conventional and tissue Doppler echocardiography in coronary slow flow phenomenon (CSFP) patients and compared to those of a control group. STUDY DESIGN Sixty patients (49 male; mean age 52.4±12.1) in whom CSFP was detected during coronary angiography study and 30 volunteers with normal coronary arteries (21 males; mean age 50.2±12.1) were included in this study. CSFP was determined using the TIMI frame count (TFC) method. TIMI frame count was calculated in each coronary artery using the TFC method. Left ventricular systolic and diastolic function was assessed by conventional echocardiography and tissue Doppler imaging. TFC correlation between diastolic function parameters was measured. RESULTS Baseline demographic and laboratory results did not differ significantly between the groups. TIMI frame counts were greater in the CSFP group compared to controls (p<0.001). Left ventricular ejection fraction (65.93±8.06% vs 66.63±5.96%), E/A ratio (1.11±0.36 vs 1.22±0.33), and isovolumetric relaxation time (IVRT) (85±17 cm/s vs 84±13 cm/s) measured with conventional echocardiography showed no significant difference between the two groups. Em (7.0±2.1 cm/s vs 7.4±1.7 cm/s), Am (7.4±2.0 cm/s vs 7.0±1.4 cm/s) and E/Em (10±3 vs 10±1) measured with tissue Doppler echocardiography showed no significant difference between the two groups. Corrected TIMI frame count for the left descending coronary artery (cLAD) and mean TFC were not correlated with the E/A ratio, deceleration time (DT), IVRT, or E/Em ratio. CONCLUSION Left ventricular systolic and diastolic functions were preserved in CSFP.

Ozone preconditioning attenuates contrast-induced nephropathy in rats.

BACKGROUND Contrast-induced nephropathy (CIN) is an important complication of vascular interventions. Ozone therapy can induce tolerance to ischemic insults, a phenomenon known as ozone oxidative preconditioning (OOP). The aim of this study was to investigate the effects of OOP on CIN. MATERIALS AND METHODS Thirty-two Wistar rats were randomized into four groups (n = 8). The control group had intravenous saline injection. The contrast media (CM) group had intravenous meglumine/sodium diatrizoate injection to form CIN. The ozone (O3) group received intraperitoneal ozone for 5 d before the induction of CIN. The oxygen (O2) group was given an equal amount of oxygen for 5 d before the induction of CIN. The animals were sacrificed 48 h after the administration of contrast agent or saline. Kidneys were harvested, and blood samples were obtained. Renal function tests, serum and renal tissue malondialdehyde (MDA), and nitric oxide (NO) levels and renal oxidant system parameters were determined. Histologic examination was performed for renal injury. RESULTS Serum blood urea nitrogen (BUN), creatinine, and serum and renal MDA were increased after contrast exposure. Renal NO was decreased, and there was prominent tubular necrosis in the CM group. Serum BUN, creatinine, serum and renal MDA, and grade of tubular necrosis were decreased in the O3 group as compared with those in the CM group. The levels of serum and renal NO and renal total antioxidant system in O3 group were higher than the levels in the CM group. CONCLUSIONS OOP attenuates experimental CIN. This effect is suggested to be mediated by reinforcement of renal antioxidant defenses and maintenance of renal NO levels.

The usefulness of carvedilol and nebivolol in preventing contrast nephropathy in rats

Abstract Background: Oxidative stress and vasoconstriction appear to be important components of contrast nephropathy (CN) pathogenesis, and both carvedilol and nebivolol are known to have vasodilatory and antioxidant effects. Aims: This study aimed to investigate whether carvedilol and nebivolol play preventive roles against developing CN and to compare the effects of each. Materials and methods: Wistar albino rats were divided into control (C, n = 6), contrast material (CM, n = 6), carvedilol (CV, n = 7), carvedilol + contrast material (CV + CM, n = 7), nebivolol (N, n = 7), and nebivolol + contrast (N + CM, n = 7) groups. Following 3 days of dehydration, 6 mL/kg diatrizoate was administered to each rat. Carvedilol was given at a dose of 2 mg/kg and nebivolol at a dose of 1 mg/kg by way of oral gavage. After scarification, total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD) were studied in renal tissue. Histopathological findings were graded as mild (+), moderate (++), and severe (+++). Results and discussion: Most of the histopathological findings and MDA levels were significantly higher in the CM group than that in the C, CVCM, and NVCM groups, whereas there was no significant difference between the C, CVCM and NVCM groups. TAC level in the CM group was significantly lower than in all other groups. There was no difference in SOD among groups. Conclusions: Carvedilol and nebivolol both prevent development of nephropathy related to CMs by decreasing oxidative stress. Neither is superior to the other.

S100A1 as a Potential Diagnostic Biomarker for Assessing Cardiotoxicity and Implications for the Chemotherapy of Certain Cancers

This study examined the value of blood marker S100A1 in detecting cardiotoxicity induced by chemotherapy agents; trastuzumab and lapatinib, in normal rat heart. The rats were divided into three groups: control (n = 8, no treatment), T (n = 8, one time ip treatment with 10 mg/kg trastuzumab) and L (n = 8, oral treatment with 100 mg/kg/day lapatinib for 7 days). The activities of oxidative stress parameters Malondialdehyde (MDA), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH) were measured from the extracted cardiac tissues. The levels of troponinI and S100A1 expressions were measured from blood samples. All biomarkers responded to the treatments as they exhibited alterations from their normative values, validating the chemically induced cardiotoxicity. S100A1 expression attenuated significantly (75%), which made the sensitive detection of cardiotoxicity feasible. Assessment of cardiotoxicity with S100A1 may be a valuable alternative in clinical oncology of cancers in some organs such as breast and prostate, as they do not overexpress it to compete against.

Association between hematologic parameters and in-hospital mortality in patients with infective endocarditis

Early and accurate risk prediction is an important clinical demand in patients with infective endocarditis (IE). The platelet‐to‐lymphocyte ratio (PLR) is an independent predictor of worse prognosis in various cardiovascular diseases. The aim of this study was to determine the value of PLR in the prediction of in‐hospital mortality among IE patients. We retrospectively analyzed the clinical, laboratory, and echocardiographic data of 59 adult patients with definite IE and in 40 adult controls. In‐hospital mortality occurred in 16 (27%) patients. Vegetation size, levels of high‐sensitive C‐reactive protein and procalcitonin, neutrophil‐to‐lymphocyte ratio, and PLR were significantly higher in the in‐hospital‐mortality‐positive group than in the in‐hospital‐mortality‐negative group (p = 0.004, p = 0.009, p = 0.030, p = 0.001, and p = 0.008, respectively). Lymphocyte count was, however, significantly lower in the in‐hospital‐mortality‐positive group (p = 0.004). In the receiver‐operating characteristic analysis, PLRs over 191.01 predicted in‐hospital mortality with 56.3% sensitivity and 81.4% specificity [area under the curve 0.725, 95% confidence interval (CI) 0.594–0.833; p = 0.0027]. In the multivariate analysis, PLR was found to be an independent predictor of in‐hospital mortality in patients with IE (odds ratio 1.022, 95% CI 1.003–1.042; p = 0.021). In conclusion, higher PLR may predict in‐hospital mortality in patients with IE.

Blood count parameters can predict the severity of coronary artery disease

Background/Aims Because of the inflammatory nature of coronary artery disease (CAD), both platelets and white blood cells have been investigated for years. The aim of this study was to investigate the relationships between some prominently hematologic blood count parameters (mean platelet volume [MPV], neutrophil to lymphocyte ratio [NLR]) and the severity of CAD by using Gensini scores. Methods A total of 194 patients, who had undergone coronary angiography, enrolled in this study. The control group consisted of 42 patients who had normal coronary arteries. Remaining CAD patients were divided into two groups according to their Gensini scores. Results NLR and MPV were higher in the severe atherosclerosis group compared with the mild atherosclerosis group (p = 0.007, p = 0.005, respectively). The Gensini score showed significant correlations with NLR (r = 0.20, p = 0.011), MPV (r = 0.23, p = 0.004) and high density lipoprotein cholesterol (r = –0.161, p = 0.047). Using a cut-off level of 2.54, NLR predicted severe atherosclerosis with a sensitivity of 74% and specificity of 53% (area under curve [AUC], 0.627; 95% confidence interval [CI], 0.545 to 0.704; p = 0.004). MPV values above 10.4 predicted severe atherosclerosis with a sensitivity of 39% and specificity of 90% (AUC, 0.631; 95% CI, 0.549 to 0.708; p = 0.003). In the multiple logistic regression analysis, high levels of NLR (odds ratio [OR], 1.450; 95% CI, 1.080 to 1.945; p = 0.013) and MPV (OR, 1.622; 95% CI, 1.147 to 2.295; p = 0.006) were found to be independent predictors of severe atherosclerosis. Conclusions Our study suggests that both NLR and MPV are predictors of severe atherosclerosis and may be used for the prediction and identification of cardiac risks in CAD patients.