Browsing by Author "Sekeroglu, Mehmet Ramazan"

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Characteristics of Resveratrol and Serotonin on Antioxidant Capacity and Susceptibility To Oxidation of Red Blood Cells in Stored Human Blood in a Time-Dependent Manner
(Sage Publications Ltd, 2018) Huyut, Zubeyir; Sekeroglu, Mehmet Ramazan; Balahoroglu, Ragip; Huyut, Mehmet Tahir
Objective In stored red blood cells (RBCs), which are used in diseases (e.g., acute blood loss and leukaemia), storage lesions arise by oxidative stress and other factors over time. This study investigated the protective effects of resveratrol and serotonin on stored RBCs. Methods Blood from each donor (n=10) was placed in different bags containing 70mL of citrate phosphate dextrose (total volume: 500mL) and divided into three groups (n=30): control, 60 mu g/mL resveratrol, and 60 mu g/mL serotonin. Malondialdehyde (MDA) and glutathione (GSH) levels, activity of glutathione peroxidase (GSH-Px), catalase, and carbonic anhydrase (CA), and susceptibility to oxidation in RBCs, and pH in whole blood were measured at baseline and on days 7, 14, 21, and 28. Results MDA levels and susceptibility to oxidation were increased in all three groups time-dependently, but this increase was greater in the serotonin group than in the other groups. Activity of GSH-Px, CAT, and CA, as well as GSH levels, were decreased in the control and serotonin groups time-dependently, but were significantly preserved in the resveratrol group. The pH was decreased in all groups time-dependently. Conclusion Our study shows that resveratrol attenuates susceptibility to oxidation of RBCs and protects their antioxidant capacity, and partially preserves CA activity time-dependently.
Determining Oxidant and Antioxidant Status in Patients With Genital Warts
(Taylor & Francis Ltd, 2015) Cokluk, Erdem; Sekeroglu, Mehmet Ramazan; Aslan, Mehmet; Balahoroglu, Ragip; Bilgili, Serap Gunes; Huyut, Zubeyir
Objectives: Warts are abnormal skin growths caused by human papilloma virus (HPV) infections within the skin of patients. Genital warts usually appear in the perianal and perigenital regions. Asymptomatic warts may be activated after years and may damage natural immunity. The inflammation that occurs during this process may lead to an imbalance between the prooxidant and the antioxidant systems. The aim of this study was to investigate erythrocyte glutathione peroxidase (GSH-Px) activity, serum paraoxonase enzyme levels, and oxidative stress levels in patients with genital warts. Patients and Methods: In total, 32 patients with genital warts and 35 healthy subjects were included in this study. Erythrocyte GSH-Px activity, serum catalase activity, and paraoxonase enzyme, and malondialdehyde (MDA) levels were determined. Results: Erythrocyte GSH-Px activity, serum MDA levels, and catalase activity were significantly higher in patients with genital warts than in controls (P < 0.01, P < 0.05, and P < 0.05, respectively). However, serum paraoxonase enzyme levels were not significantly different between groups (P > 0.05). Serum triglyceride levels were significantly lower in patients with genital warts than in controls (P < 0.01). However, there were no statistically significant differences between groups with respect to total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol levels (all P > 0.05). Conclusions: Our data suggest that oxidative stress is increased in genital warts. Increased oxidative stress levels may contribute to the pathogenesis of genital warts, and prolonged HPV infection due to chronic inflammation could also affect oxidative stress.
The Effect of Non-Enzymatic Glycation of Extracellular Matrix Proteins on Axonal Regeneration in Vitro
(Springer, 2006) Ozturk, Gurkan; Sekeroglu, Mehmet Ramazan; Erdogan, Ender; Ozturk, Mustafa
Non-enzymatic glycation of peripheral nerve extracellular matrix (ECM) may contribute to the development of diabetic distal sensory neuropathy (DNP). We investigated the relative importance of glycation of collagen types I and IV, laminin and fibronectin in DNP-related impairment in peripheral nerve regeneration. Dorsal root ganglia (DRGs) from young adult mice were embedded in collagen type I modified by 10% substitution with normal or glycated forms of the proteins and incubated for 3 days. Outgrowth of axons and migration of cells into the ECM were quantified. Mean length of growing axons was significantly reduced by glycation of laminin and collagen type IV. The sum of lengths of all axons from each DRG was greatly reduced with glycated laminin, collagen types IV and I. Glycation of fibronectin had no effect on axonal growth. The number of migrating cells was not affected by glycation. We conclude that non-enzymatic glycation of laminin and collagen types IV and I (in decreasing order) impairs peripheral nerve regeneration in vitro.
The Importance of Oxidative Stress in Patients With Chronic Renal Failure Whose Hypertension Is Treated With Peritoneal Dialysis
(Wiley, 2011) Demirci, Serafettin; Sekeroglu, Mehmet Ramazan; Noyan, Tevfik; Koceroglu, Rusen; Soyoral, Yasemin Usul; Dulger, Haluk; Erkoc, Reha
Increased oxidative stress is a well-known phenomenon in dialysis patients. However, the contribution of hypertension to the oxidative stress in peritoneal dialysis patients has not yet been assessed. The present study aimed to investigate if hypertension had an additional effect on oxidative stress in peritoneal dialysis patients. A total of 50 patients treated with peritoneal dialysis were divided into two groups: The patients with mean of last three blood pressure results as 135/90 mmHg and above were considered hypertensive, the patients with lower blood pressure were considered normotensive. The control group included 25 healthy individuals. Serum malondialdehyde (MDA), advanced oxidation protein product (AOPP), myeloperoxidase (MPO), catalase (CAT) and glutathione peroxidase (GSH-Px) levels were measured in all groups. MDA level, an indicator of lipid peroxidation, was significantly higher in the hypertensive group compared to the control group, while the increase in the normotensive group was not significant. However, the difference between the hypertensive and normotensive groups was significant. The levels of AOPP, an indicator of protein oxidation level, and MPO, an indicator of neutrophil activation, were not different between the groups, while the activities of antioxidant CAT and GSH-Px decreased in both normotensive and hypertensive groups compared to the control group, and there was no significant difference between the patient groups. This study shows that both normotensive and hypertensive peritoneal dialysis patients have increased-oxidative stress and decreased antioxidant levels and hypertension might have an additional effect on oxidative stress by increasing MDA level in peritoneal dialysis patients. Copyright (C) 2011 John Wiley & Sons, Ltd.
Investigation of the Relationship Between Serum Levels of Cotinine and the Renal Function in Active and Passive Smokers
(informa Healthcare, 2011) Dulger, Haluk; Donder, Ahmet; Sekeroglu, Mehmet Ramazan; Erkoc, Reha; Ozbay, Bulent
Objective: We have investigated the effects of active and passive smoking on renal functions in terms of glomerular filtration rate, microalbuminuria, and beta-2 microglobulin excretion. Design and method: The volunteers included in this study were classified into three groups as active smokers (n = 24), passive smokers (n = 20), and controls (n = 20). Blood and urine samples were collected from all groups. Serum glucose, urea, creatinine, and cotinine levels in the collected blood samples were measured. Also, microalbumin, beta-2 microglobulin, and creatinine levels were measured in the collected urine samples. Results: Serum cotinine levels were found to be higher in both passive and active smokers when compared with controls (p < 0.01), whereas urinary microalbumin and creatinine levels were significantly higher in active smokers (p < 0.01). The urinary microalbumin/creatinine ratio was significantly increased in both active and passive smokers compared with controls. Conclusion: The kidney and the glomerular functions may be affected even by passive smoking. In addition, increased microalbumin/creatinine ratio may be a sign of increased atherosclerosis risk in these persons.
The Levels of Nitrite, Nitrate and Lipid Peroxidation in Diabetic Mouse Brain: the Effect of Melatonin and Pentoxifylline
(Taylor & Francis Ltd, 2022) Yalcinkaya, Ahmet S.; Sekeroglu, Mehmet Ramazan; Huyut, Zubeyir; Cokluk, Erdem; Ozbek, Hanefi; Ozturk, Gurkan; Balahoroglu, Ragip
Objective: This study investigated the relationship between diabetes (DM) and nitrite, nitrate and MDA levels and effect of melatonin and pentoxifylline. Methods: Sixty mice were randomly divided into four groups. Control: no action; Diabetes group (DM): after fasting-blood-glucose (FBG) was measured, 150 mg/kg alloxane was applied intraperitoneally three-times every other day; Diabetes + Melatonin (DM + MLT) and Diabetes + Pentoxifylline groups (DM + PTX): following the same procedures with DM, 10 mg/kg melatonin and 50 mg/kg pentoxifylline were administered subcutaneously six days, respectively. Following FBG analysis, brain tissues were taken under the anaesthesia. Nitrite, nitrate and MDA levels were measured. Results: In the all groups with alloxane, FBG were higher than in before application (p < .05). Also, FBG, nitrite, nitrate and MDA levels in the DM + MLT and DM + PTX groups were lower than in the DM (p < .05). Conclusions: Nitrite and nitrate may be related to etiopathogenesis of DM, and pentoxifylline and especially melatonin relatively decrease nitrite, nitrate and lipid peroxidation.
Oxidative Dna Damage To Sperm Cells and Peripheral Blood Leukocytes in Infertile Men
(int Scientific Literature, inc, 2016) Taken, Kerem; Alp, Hamit Hakan; Eryilmaz, Recep; Donmez, Muhammet Irfan; Demir, Murat; Gunes, Mustafa; Sekeroglu, Mehmet Ramazan
Background: Oxidative DNA damage is associated with male infertility. The aim of this study was to evaluate the oxidative DNA damage of sperm cells and blood leukocytes and to determine the levels of MDA and NO levels in seminal and blood plasma of idiopathic infertile men. Material/Methods: The study enrolled 52 patients, including 30 infertile and 22 fertile men. MDA, NO, and 8-OHdG/10(6)dG were estimated using spectrophotometry and high-pressure liquid chromatography ( HPLC)-based methods in seminal and blood plasma. The association with the sperm parameters was assessed, particularly sperm counts and motility. Results: The mean sperm concentration and sperm motility of the fertile men were significantly higher than that of the infertile men. The mean MDA and NO concentration in the seminal and blood samples of the infertile men were higher than that of fertile men. Also, the mean numbers of sperm cells and leukocytes 8-OHdG/10(6)dG of the infertile men were significantly higher than that of fertile men (p=0.04 and p<0.001, respectively). Sperm motility and sperm count were negatively correlated with leukocyte and sperm cell 8-OHdG/10(6)dG ratio. However, progressive motility was significantly negatively correlated with sperm cell and leukocyte 8-OHdG/10(6)dG ratio (R=-0.357, p=0.026; R=-0.388, p=0.024, respectively). Conclusions: Oxidative stress is an important factor in male infertility. Therefore, biochemical detection of 8-OHdG/10(6)dG in sperm cells and blood leukocytes may be an additional tool in the diagnosis of male infertility.
The Relationship of Oxidation Sensitivity of Red Blood Cells and Carbonic Anhydrase Activity in Stored Human Blood: Effect of Certain Phenolic Compounds
(Hindawi Ltd, 2016) Huyut, Zubeyir; Sekeroglu, Mehmet Ramazan; Balahoroglu, Ragip; Karakoyun, Tahsin; Cokluk, Erdem
It has been reported that many modifications occur with the increase of oxidative stress during storage in erythrocytes. In order to delay these negative changes, we evaluated whether the addition of substances likely to protect antioxidant capacity in stored blood would be useful. Therefore, we investigated the effects of resveratrol, tannic acid, and caffeic acid in lipid peroxidation and antioxidant capacity of erythrocytes in stored blood. Donated blood was taken into four CPD containing blood bags. One bag was used as the control, and the others were supplemented with caffeic acid (30 mu g/mL), resveratrol (30 mu g/mL), and tannic acid (15 mu g/mL), respectively. Erythrocyte lipid peroxidation, sensitivity to oxidation, glutathione levels and carbonic anhydrase, glutathione peroxidase, and catalase activities were measured on days 0, 7, 14, 21, and 28. In the control group, erythrocyte malondialdehyde levels and sensitivity to oxidation were increased whereas glutathione, glutathione peroxidase, and catalase levels were decreased (P < 0.05). Resveratrol and caffeic acid prevented malondialdehyde accumulation and preserved glutathione, glutathione peroxidase, and catalase activities in erythrocytes. We demonstrated that resveratrol, caffeic acid, and tannic acid in stored blood could decrease the sensitivity to oxidation of erythrocytes in vitro but did not exhibit such effects on CA activity.
Serum Advanced Oxidation Protein Products, Myeloperoxidase and Ascorbic Acid in Pre-Eclampsia and Eclampsia
(Wiley, 2006) Noyan, Tevfik; Guler, Ayse; Sekeroglu, Mehmet Ramazan; Kamaci, Mansur
Background: Activation products from neutrophils and the complement system might cause endothelial dysfunction, which is central to the aetiology of pre-eclampsia. This study aimed to investigate the activity of myeloperoxidase (MPO), and its association with advanced oxidation protein products (AOPP), in women with pre-eclampsia and eclampsia. Materials and method: Twenty-one pregnant women with pre-eclampsia, 11 pregnant women with eclampsia and 19 healthy pregnant women were studied. Serum levels of malondialdehyde (MDA), AOPP, ascorbic acid (AA) and activities of MPO and catalase (CAT) were measured using a colorimetric method. Results: The MDA level was significantly higher in the pre-eclampsia (3.15 +/- 0.28 nmol/mL) and eclampsia (4.01 +/- 0.66 nmol/mL) groups than in controls (1.85 +/- 0.18 nmol/mL); the difference between MDA levels in the pre-eclampsia and eclampsia groups was not statistically significant. MPO activity was significantly higher in the eclampsia (347.59 +/- 88.06 U/L) group than in the pre-eclampsia (196.17 +/- 30.8) and control (93.22 +/- 9.52) groups, and there was also no significant difference in these levels between the pre-eclampsia and control groups. CAT activity was significantly higher in the pre-eclampsia (166.35 +/- 31.75 U/L) and eclampsia (166.98 +/- 40.31 U/L) groups than in controls (81.28 +/- 7.41 U/L), and AA level was significantly higher in the pre-eclampsia (0.54 +/- 0.15 mg/dL) group than in controls (0.18 +/- 0.01 mg/dL); the differences in AA and CAT activity between the pre-eclampsia and eclampsia groups were not statistically significant. AOPP levels did not change significantly among the control, pre-eclampsia and eclampsia groups (106.88 +/- 5.62, 98.89 +/- 6.47, 111.89 +/- 6.8 mu mol/L, respectively). Conclusions: We suggest that increased oxidative stress might contribute to the pathophysiological mechanisms of pre-eclampsia and eclampsia, and that AA and CAT might have a protective role via free radical-scavenging properties. However, further study is needed.
The Serum Interleukin-6 and Tumor Necrosis Factor-Α Levels and Their Relationship With Antithrombin-Iii and Von Willebrand Factor in Preeclampsia
(Galenos Yayincilik, 2006) Noyan, Tevfik; Bursal, Ercan; Sekeroglu, Mehmet Ramazan; Dulger, Haluk; Kamaci, Mansur
Objective: Preeclampsia, characterized by changes in the placenta and uteroplacental vasculature, is the most frequent complication of pregnancy. It is argued that an overproduction of placental cytokines may be associated with the pathophysiological changes found in preeclampsia. In this study, it is aimed to determine the levels of both pro-inflammatory (tumor necrosis factor-alpha) and immunoregulatory (interleukin-6) cytokines and their relationships with von Willebrand factor and anti-thrombin III from both preeclamptic and healthy pregnant women. Material and Methods: Twenty-five pregnant women with preeclampsia and 25 healthy pregnant women were included in the study. The fasting blood samples were obtained at eight o'clock in the morning from the both groups and interleukin-6, tumor necrosis factor-alpha, von Willebrand factor and anti-thrombin III levels were measured. From the preeclamptic patients blood samples were obtained at twelve o'clock midnight to determine the diurnal variation in these two cytokine levels. Results: As compared to healthy pregnant group, levels of interleukin-6 and anti-thrombin III were significantly lower and von Willebrand factor level was significantly higher in the preeclamptic group (p< 0.05). Tumor necrosis factor-alpha level did not differ significantly between the two groups. Interleukin-6 and tumor necrosis factor-alpha levels did not show significant diurnal variation in preeclamptic group. A significant positive correlation was found between the tumor necrosis factor-alpha levels measured in the morning and night samples in the preeclamptic group (p< 0.01, r=0.701). Also, a significant positive correlation was found between the tumor necrosis factor-alpha and von Willebrand factor levels in healthy pregnant group (p< 0.05, r=0.648). Conclusions: These findings suggest that preeclampsia is associated with decreased interleukin-6, and anti-thrombin III, and with increased von Willebrand factor levels.
Serum Lipid Concentrations in Obsessive-Compulsive Disorder Patients With and Without Panic Attacks
(Canadian Psychiatric Assoc, 2004) Agargun, Mehmet Yucel; Dulger, Haluk; Inci, Rifat; Kara, Hayrettin; Ozer, Omer Akil; Sekeroglu, Mehmet Ramazan; Besiroglu, Lutfullah
Objective: To examine serum lipid levels in patients with obsessive-compulsive disorder (OCD) and to test whether panic symptoms affect lipid concentrations in OCD patients. Methods: We assessed 33 OCD patients and 33 healthy control subjects matched for sex and age. Results: OCD patients had higher low-density lipoprotein, very-low-density lipoprotein, and tryglyceride levels, but lower high-density lipoprotein levels, than normal control subjects. We also found that only OCD patients with panic attacks had higher serum lipid concentrations, compared with normal control subjects. Serum lipid levels of pure OCD patients did not differ from control values. Conclusion: These findings suggest that high serum lipid concentrations are related to panic anxiety rather than other symptoms of the illness. (Can J Psychiatry 2004;49:776-778)
Stimulating Effects of Vardenafil, Tadalafil, and Udenafil on Vascular Endothelial Growth Factor, Angiogenesis, Vitamin D3, Bone Morphogenic Proteins in Ovariectomized Rats
(Taylor & Francis Ltd, 2022) Huyut, Zubeyir; Alp, Hamit Hakan; Bakan, Nuri; Yildirim, Serkan; Sekeroglu, Mehmet Ramazan
Objective: This study investigated the effect of vardenafil, tadalafil, and udenafil from phosphodiesterase-5 inhibitors (PDE-5Is) on bone morphogenic-protein (BMP)2 and 4 levels, along with angiogenesis in ovariectomized rat's kidney. Method: Rats were randomly divided into five groups (n = 10). Sham: abdomen was opened, and closed. OVX: ovaries were removed. OVX + vardenafil, OVX + tadalafil, and OVX + udenafil groups: ovaries were removed and closed, and after 6 months from postoperative, 10 mg/kg of vardenafil, tadalafil, and udenafil were administrated as daily a single-dose for 60 days, respectively. Histopathologic and immunohistochemical examinations were performed for angiogenesis, and biochemical analysis for vascular endothelial growth-factor (VEGF), VitaminD(3), BMP2 and 4 levels in rat's kidney. Results: VEGF, BMP2 and 4, VitaminD(3), and angiogenesis were high in the all inhibitor groups compared with the sham and OVX (p < .05). However, BMP4 levels were only high in the OVX + tadalafil group (p < .05). Conclusion: The results indicated that vardenafil, udenafil, and especially tadalafil increased VEGF, BMP2, and VitaminD(3) levels.
The Susceptibility of Erythrocytes To Oxidation During Storage of Blood: Effects of Melatonin and Propofol
(Pergamon-elsevier Science Ltd, 2012) Sekeroglu, Mehmet Ramazan; Huyut, Zubeyr; Him, Aydin
Objectives: We investigated the effects of melatonin and propofol in lipid peroxidation and antioxidant capacity of erythrocytes in stored bloods. Design and methods: Donated blood was taken into three citrate-phosphate-dextrose containing blood bags. One bag was used as control, the others were added either melatonin or propofol. Erythrocyte lipid peroxidation and antioxidant capacity and their sensitivity to in vitro oxidation were measured on days 0, 7, 14, 21 and 28. Results: In control group, erythrocyte malondialdehyde levels and sensitivity to in vitro oxidation were increased whereas glutathione, glutathione peroxidase and superoxide dismutase levels were decreased. Melatonin prevented malondialdehyde accumulation and preserved glutathione, glutathione peroxidase and superoxide dismutase levels. Propofol preserved glutathione and glutathione peroxidase levels but did not affect catalase and superoxide dismutase activities. Conclusions: We showed that melatonin in stored blood could prevent lipid peroxidation and increase the resistance of erythrocytes to in vitro oxidation while propofol did not show such effects. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
The Susceptibility To Autoxidation of Erythrocytes in Diabetic Mice: Effects of Melatonin and Pentoxifylline
(Wiley, 2017) Sekeroglu, Mehmet Ramazan; Huyut, Zubeyir; Cokluk, Erdem; Ozbek, Hanefi; Alp, Hamit Hakan
Oxidative stress had a great importance in development of complications in diabetes. We investigated effects of melatonin and pentoxifylline in diabetic mice. Swiss albino mice (n=40) were divided into four groups: alloxan-induced diabetes mellitus (DM), alloxan-induced diabetes with melatonin supplementation (DM+MLT), alloxan-induced diabetes with pentoxifylline supplementation (DM+PTX), and control. Glutathione-peroxidase (GSH-Px) activity, malondialdehyde (MDA) and reduced glutathione (GSH) levels, and susceptibility to oxidation of erythrocytes were measured. MDA levels were higher than control in the DM and DM+MLT. The DM had more MDA level than the DM+MLT and DM+PTX (P<0.001). After in vitro oxidation, MDA levels of all groups were found higher than the control. However, they were significantly lower than the DM in DM+PTX and DM+MLT (P<0.001). Although GSH levels of the DM and DM+PTX were less than the control, GSH-Px activity of the DM was lower than the control and DM+PTX (P<0.05). We suggest that there is increased oxidative stress and compromised antioxidant status of erythrocytes in diabetes; however, it can be effectively prevented by melatonin or pentoxifylline supplementation.
Within-Subject and Between-Subject Biological Variation of First Morning Void Urine Amino Acids in 12 Healthy Subjects
(Walter de Gruyter Gmbh, 2020) Alp, Hamit Hakan; Akbay, Halil Ibrahim; Cokluk, Erdem; Huyut, Zubeyir; Keskin, Siddik; Sekeroglu, Mehmet Ramazan
Background: Urine amino acid analysis is used for the assessment of various diseases. The aim of this study was to estimate the valid biological variation (BV) components (within- and between-subjects) required for the safe clinical application of free urine amino acids. Methods: First morning void urine samples were taken from 12 healthy subjects (five females, seven males) once a week for 10 consecutive weeks, and amino acid analysis was performed using an Agilent 6470 triple quadrupole tandem mass spectrometer instrument. The obtained data were subjected to normality, outlier and variance homogeneity analyses prior to coefficient of variation (CV) analysis. Within- and between-subject BV values (CVI and CVG) of 39 amino acids were determined for all subjects. In addition, the index of individuality (II), reference change value (RCV), imprecision, bias and total error were estimated using BV data obtained from our study. Results: The CVI values ranged from 8.9 (histidine) to 36.8% (trans-4-hydroxyprolin), while the CVG values ranged from 25.0 (1-methyl-L-histidine) to 63.3% (phenylalanine). The II value of most amino acids was less than 0.6 and ranged between 0.21 and 0.88. The imprecision, bias and total error ranged between 4.45 and 16.6, between 7.69 and 16.6, and between 18.4 and 43.2, respectively. Conclusions: This study, designed according to a rigorous protocol, has the feature of being the first to give information about BV data of urine amino acids. We believe that the reference intervals have a limitation in the evaluation of consecutive results from an individual, so the use of RCV would be more appropriate.
Zaprinast and Avanafil Increase the Vascular Endothelial Growth Factor, Vitamin D3, Bone Morphogenic Proteins 4 and 7 Levels in the Kidney Tissue of Male Rats Applied the Glucocorticoid
(Taylor & Francis Ltd, 2022) Huyut, Zubeyir; Bakan, Nuri; Akbay, Halil Ibrahim; Yildirim, Serkan; Sekeroglu, Mehmet Ramazan
Objective: This study investigated effect of zaprinast and avanafil on vascular endothelial growth factor (VEGF), bone morphogenic protein (BMP) 4 and 7, and vitamin D-3 levels against the negative effect of dexamethazone. Method: Rats were randomly divided into four groups (n = 6). Control: Empty a syringe was immersed and removed subcutaneously. Dexamethasone (DEX): 120 mu g/kg DEX was injected subcutaneously once a day for 28 days. DEX + zaprinast and DEX + avanafil groups: 10 mg/kg zaprinast and avanafil were administrated to rats in addition to the same procedure in the DEX, respectively. VitaminD(3), VEGF, BMP4 and 7 levels by enzyme linked immunosorbent assay (ELISA) and angiogenesis by histopathological/immunohistochemical were evaluated. Results: BMP4 values in the DEX were lower than the other groups (p < .05). DEX + zaprinast and DEX + avanafil exhibited an increase in all the parameters compared to the control and DEX (p < .05). However, these were not significant for the DEX + zaprinast (p > .05). Also, there was a significant increase in angiogenesis in the DEX + zaprinast and DEX + avanafil. Conclusion: Zaprinast and significantly avanafil induced vitamin D-3, BMP4 and 7 levels by increasing angiogenesis in renal.