Sukru Ulusoy

Anti‐apoptotic and anti‐oxidant effects of grape seed proanthocyanidin extract in preventing cyclosporine A‐induced nephropathy

Aim:  Although the pathogenesis of cyclosporine (CsA) nephropathy is not completely understood, it is attributed to oxidative damage and apoptosis. Grape seed proanthocyanidin extract (GSPE) is a molecule with anti‐oxidant and anti‐apoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing CsA nephropathy.

How Does Colistin-Induced Nephropathy Develop and Can It Be Treated?

ABSTRACT Colistin is an old antibiotic used in the treatment of Gram-negative infections. It was once suspended because of its nephrotoxic effect but has since been reintroduced due to multidrug-resistant bacterial infections. The pathogenesis of colistin-associated nephropathy has not been clarified, and there is currently no effective therapeutic or prophylactic agent available. The aim of this study was to investigate the roles of caspase-associated apoptosis and caspase 1, calpain 1, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) expression in the pathogenesis of colistin-associated nephrotoxicity and the effect of grape seed proanthocyanidin extract (GSPE) in preventing it. Twenty-four rats were divided into three groups: control, colistin, and colistin plus GSPE (colistin+GSPE). Colistin-associated nephropathy was induced by the administration of 300,000 IU/kg of body weight/day colistin intraperitoneally for 7 days. The experiment was discontinued on the seventh day. Blood was collected for measurements of blood urea nitrogen (BUN) and creatinine levels. Histopathological examination of kidney tissue and caspase 1 and 3, iNOS, eNOS, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and calpain 1 staining was also performed. Significant increases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed for the colistin group compared to the control group. Significant decreases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed in the colistin+GSPE group compared to the colistin group. Our study shows, for the first time in the literature, that caspase-mediated apoptosis, iNOS, caspase 1, and calpain 1 are involved in the pathogenesis of colistin-associated nephropathy. GSPE had a renoprotective effect, as shown by the lowered levels of these mediators.

Protective Effect of the Grape Seed Proanthocyanidin Extract in a Rat Model of Contrast-Induced Nephropathy

Aim: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute renal failure. Although it is so common, there has been no approved therapy yet. We aimed to investigate the effect of grape seed proanthocyanidin extract (GSPE) on preventing CIN. Materials and Methods: 24 rats were divided into four groups as control group, GSPE group, contrast medium (CM) group, and CM+GSPE group. The experiment was discontinued on the ninth day. Blood samples were obtained for the measurement of renal function parameters. Renal tissues of the rats were removed for the analysis of oxidative system parameters. In addition to renal histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: There was a significant increase in BUN, creatinine, malondialdehyde (MDA) levels, apoptotic index (AI) and histopathological alteration in the CM group as compared to the control group. Furthermore, BUN, creatinine, MDA, total oxidant system and oxidative stress index levels, AI as well as renal histopathological alteration were significantly decreased in the CM+GSPE group. Conclusion: For the first time in the literature, we showed that GSPE provided biochemical and histopathological improvement in CIN. Our findings revealed that this improvement was associated with the decrease in oxidative damage and apoptosis.

Antiapoptotic and Antioxidant Effects of GSPE in Preventing Cyclosporine A-Induced Cardiotoxicity

Objectives: Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity. Materials and methods: Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase. Conclusion: In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities

Amikacin-Induced Nephropathy: Is There Any Protective Way?

Amikacin is a commonly used antibacterial drug that can cause significant nephrotoxic effects in both humans and experimental animals. It has been reported that one mechanism of the toxic effects of aminoglycoside antibiotics are the result of oxidative reactions. The aim of this study is to examine the effects of N-acetylcysteine, a thiol-containing antioxidant, on renal function (serum creatinine) and morphology (renal tubular damage) in mice subjected to amikacin-induced nephrotoxicity. A total of 32 mice were equally divided into four groups that were injected with either saline, amikacin (1.2g/kg intraperitoneally), N-acetylcysteine (150mg/kg intraperitoneally for three days) plus amikacin (1.2 g/kg intraperitoneally on the third day as a single dose), or N-acetylcysteine (150mg/kg intraperitoneally). Amikacin administration led to granulovacuolar tubular degeneration in light microscopic examination and myeloid bodies, mitochondrial electron-dense material deposition, and mitochondrial swelling in the proximal tubule epithelium in the electron microscopic evaluation. N-acetylcysteine administration before amikacin injection caused significant decreases in myeloid body and mitochondrial swelling and granulovacuolar tubular degeneration formation. Serum creatinine levels did not change as a result of any treatment. The results show that N-acetylcysteine has a protective effect on nephrotoxicity induced by amikacin. Higher doses of amikacin should be tried to observe biochemical effects.

The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy.

Background/Aims: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. Methods: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. Results: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. Conclusion: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

New Marker of Platelet Activation, SCUBE1, Is Elevated in Hypertensive Patients

BACKGROUND Hypertension is associated with an increase in platelet activation and endothelial dysfunction and leads to a tendency to cardiovascular events (CVEs). Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) is a novel platelet activation marker. There are currently no studies showing the level of SCUBE1 in hypertensive patients. The purpose of this study was to determine the level of SCUBE1 in this patient group and to investigate the parameters affecting that level. METHODS Forty-five newly diagnosed, untreated, stage 1 hypertensive patients and 21 healthy individuals were included. Blood specimens were collected to determine SCUBE1, soluble CD40 ligand, prothrombin time, partial thromboplastin time, fibrinogen, D dimer, hemogram, lipid parameters, blood urea nitrogen, creatinine, and uric acid levels. The relation between SCUBE1 level and demographic data and biochemical parameters was then investigated. RESULTS SCUBE1 and sCD40L levels obtained from plasma specimens from the hypertensive group were significantly higher than those of the control group (P < 0.001; P < 0.05, respectively). Hypertensive group blood pressure (BP) values and uric acid, low-density lipoprotein, total cholesterol, and triglyceride levels were also statistically higher than those of the control group. Parameters affecting SCUBE1 levels were systolic and diastolic BP, sCD40L, lipid parameters, and uric acid levels. CONCLUSIONS We show elevated levels of SCUBE1, a novel platelet activation marker, in primary hypertensive patients. We think that, when supported by further clinical studies, this newly described marker may be useful in the monitoring of CVEs in this patient group, in which platelet activation is known to be associated with such events.

TGF-beta and TNF-alpha producing effects of losartan and amlodipine on human mononuclear cell culture.

Aim:  The modulation of cytokine release, which affects adhesion of leucocytes to endothelial cells, and proliferation of peripheral blood mononuclear cells with antihypertensive drugs was explored.

Hemostatic and Fibrinolytic Response to Nasal Desmopressin in Hemodialysis Patients

Objective: To evaluate the effect of desmopressin (DDAVP) on hemostatic parameters during dialysis and in the interval between dialysis sessions. Subjects and Methods: Fifteen patients dialyzed twice weekly at least for 1 year and 15 healthy volunteers serving as a control group were enrolled in the study. Bleeding time, platelet count, prothrombin time, activated partial thromboplastin time, tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), euglobulin clot lysis time, protein C, protein S, fibrinogen, D-dimer, factor V, VII, VIII, IX, X and von Willebrand factor (VWF) values were studied at the beginning, at 2 and 4 h of dialysis with and without administration of DDAVP at a dose level of 2 µg/kg intranasally. Results: After dialysis, bleeding time shortened, PAI-1 and fibrinogen levels were lower, while VWF and D-dimer levels were higher. After DDAVP administration, bleeding time, PAI-1 levels were significantly lower (p < 0.01), while tPA, factor VIII and VWF levels increased significantly (p < 0.001). Conclusion: The findings indicate that DDAVP can be used for patients on dialysis with serious bleeding.

An Unusual Etiology of Erythropoietin Resistance: Hyperthyroidism

Many possible causes of resistance to human recombinant erythropoietin (rh-EPO) have been reported in patients with renal failure. This case presents an unusual cause of erythropoietin-resistant anemia in a patient with chronic renal failure. A 61-year-old male patient who was on chronic hemodialysis program due to diabetic nephropathy for seven months developed erythropoietin resistant anemia. No iron deficiency was revealed by laboratory data, no megaloblastic anemia were found by biochemical investigation, and no inflammatory states including infection or neoplastic diseases were disclosed by abdominal ultrasonography, chest X-ray, bone marrow aspiration and biopsy, or other methods (normal C-reactive protein levels). This hemodialysis patient had epoetin-resistant anemia with primary autoimmune hyperthyroidism. The anti-thyroid therapy was effective not only against the hyperthyroidism but also against his epoetin resistant anemia.