Ghrelin ameliorates neuronal damage, oxidative stress, inflammatory parameters, and GFAP expression in traumatic brain injury.

OBJECTIVE: This study investigated the effects of ghrelin on oxidative stress, working memory, inflammatory parameters, and neuron degeneration. METHODS: TBI was produced with the weight-drop technique. Rats in the G+TBI and TBI+G groups received ghrelin for 7 or 2 days, respectively. The control group received saline. On the 8th day of the study, the brain and blood tissue were taken under anesthesia. RESULTS: A significant increase in brain GSH-PX, MDA, IL-1ß, TGF-ß1, and IL-8 levels and a significant decrease in CAT levels were found in the TBI group compared to the control. Serum MDA, GSH, IL-1ß, and IL-8 levels were increased with TBI. Ghrelin treatment after TBI significantly increased the serum GSH, CAT, GSH-PX, and brain GSH and CAT levels, while it significantly decreased the serum MDA, IL-1ß, and brain MDA, TGF-ß1, and IL-8 levels. Histological evaluations revealed that ghrelin treatment led to a reduction in inflammation, while also significantly ameliorating TBI-induced neuron damage and vascular injuries. Immunohistochemistry staining showed that GFAP staining intensity was significantly increased in the cortex and hippocampus in TBI, and GFAP immunoreactivity was decreased with ghrelin treatment. CONCLUSION: The results from this study suggested that ghrelin may have curative effects on TBI.

Evaluation of cerebrospinal fluid levels for ALOX5, S100B, DEFA1, and GFAP in infectious meningitis.

BACKGROUND: The aim of this study was to determine how the levels of peptide and protein-based biomarkers in cerebrospinal fluid change in bacterial, tuberculous, and aseptic meningitis, and to determine the success of these agents in distinguishing between different types of infectious meningitis. METHODS: The levels of arachidonate-5-lipoxygenase, S100 calcium-binding protein B, defensin-α 1, and glial fibrillary acidic protein in cerebrospinal fluid samples from 20 tuberculosis, 40 bacterial, 25 aseptic meningitis patients, and 55 control groups were measured and compared using an enzyme-linked immunosorbent assay. RESULTS: The mean age of the patients was 37.9 ±â€…14.4 years. The parameter that contributed the most to the differential diagnosis of the infectious meningitis groups was S100 calcium-binding protein B. The S100 calcium-binding protein B levels were significantly higher in the tuberculous meningitis group than in the other groups, and arachidonate-5-lipoxygenase levels were significantly higher in the tuberculous meningitis and bacterial meningitis groups (P < .05). CONCLUSION: This study showed that cerebrospinal fluid arachidonate-5-lipoxygenase, and S100 calcium-binding protein B levels may differ in bacterial, aseptic, and tuberculous meningitis, and the results obtained may be quite effective as important potential biomarkers in the differential diagnosis of different types of meningitis.

Effects of fluoride on oxidative DNA damage, nitric oxide level, lipid peroxidation and cholinesterase enzyme activity in a rotenone-induced experimental Parkinson's model.

OBJECTIVE: Environmental toxins are known to be one of the important factors in the development of Parkinson's disease (PD). This study was designed to investigate the possible contribution of fluoride (F) exposure to oxidative stress and neurodegeneration in rats with PD induced by rotenone (ROT). MATERIALS AND METHODS: A total of 72 Wistar albino male rats were used in the experiment and 9 groups were formed with 8 animals in each group. ROT (2 mg/kg) was administered subcutaneously (sc) for 28 days. Different doses of sodium fluoride (NaF) (25, 50 and 100 ug/mL) were given orally (po) for 4 weeks. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), oxidative DNA damage (8-OHdG) and cholinesterase (AChE/BChE) enzyme activities were evaluated in serum and brain tissue homogenates. RESULTS: Rats treated with ROT and NaF had significant increases in serum and brain MDA, NO content, and decreases in GSH. In addition, the combination of ROT and NaF triggered oxidative DNA damage and resulted in increased AChE/BChE activity. CONCLUSIONS: Findings suggest that NaF and ROT may interact synergistically leading to oxidative damage and neuronal cell loss. As a result, we believe that exposure to pesticides in combination with NaF is one of the environmental factors that should not be ignored in the etiology of neurological diseases such as PD in populations in areas with endemic fluorosis.

Effect of ferritin, INR, and D-dimer immunological parameters levels as predictors of COVID-19 mortality: A strong prediction with the decision trees.

Background and objective: A hyperinflammatory environment is thought to be the distinctive characteristic of COVID-19 infection and an important mediator of morbidity. This study aimed to determine the effect of other immunological parameter levels, especially ferritin, as a predictor of COVID-19 mortality via decision-trees analysis. Material and method: This is a retrospective study evaluating a total of 2568 patients who died (n = 232) and recovered (n = 2336) from COVID-19 in August and December 2021. Immunological laboratory data were compared between two groups that died and recovered from patients with COVID-19. In addition, decision trees from machine learning models were used to evaluate the performance of immunological parameters in the mortality of the COVID-19 disease. Results: Non-surviving from COVID-19 had 1.75 times higher ferritin, 10.7 times higher CRP, 2.4 times higher D-dimer, 1.14 times higher international-normalized-ratio (INR), 1.1 times higher Fibrinogen, 22.9 times higher procalcitonin, 3.35 times higher troponin, 2.77 mm/h times higher erythrocyte-sedimentation-rate (ESR), 1.13sec times longer prothrombin time (PT) when compared surviving patients. In addition, our interpretable decision tree, which was constructed with only the cut-off values of ferritin, INR, and D-dimer, correctly predicted 99.7% of surviving patients and 92.7% of non-surviving patients. Conclusions: This study perfectly predicted the mortality of COVID-19 with our interpretable decision tree constructed with INR and D-dimer, especially ferritin. For this reason, we think that it may be important to include ferritin, INR, and D-dimer parameters and their cut-off values in the scoring systems to be planned for COVID-19 mortality.

Determination of Serum Differential Carnitine Ester Levels in HIV(+) Patients: A Cross-Sectional Study.

OBJECTIVE: It has been reported that carnitine deficiency is observed in various viral infections and in the follow-up of the prognosis of some diseases. In this cross-sectional study, we aimed to determine how carnitine ester derivatives change in HIV-positive patients. MATERIALS AND METHODS: In this study, 25 HIV-infected patients who applied to Harran University Faculty of Medicine Education Research and Practice Hospital Infectious Diseases and Clinical Microbiology Outpatient Clinic and who did not receive any antiretroviral treatment, as well as 25 healthy volunteers were included in the study. Carnitine ester levels in serum samples were measured by Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) method (Shimadzu North America, Columbia, MD, USA). RESULTS: While suberoylcarnitine (C8DC), myristoleylcarnitine (C14:1), tetradecadienoylcarnitine (C14:2), palmitoleylcarnitine (C16:1), and linoleylcarnitine (C18:2) levels in HIV(+) patients were quite low compared to the control group, tiglylcarnitine (C5:1) levels were high (p ≤ 0.05). In addition, C5:1 and C14:2 index parameters according to VIP score, and C5:1 and C14:1/C16 index parameters according to ROC analysis were determined as markers with high potential to distinguish HIV(+) patients from healthy volunteers. CONCLUSION: This study showed that levels of acylcarnitine derivatives might be altered in HIV(+) patients, and the results obtained may contribute to a better understanding of carnitine metabolism.

Effect of curcumin on lipid profile, fibrosis, and apoptosis in liver tissue in abemaciclib-administered rats.

Abemaciclib (ABEM) is an important antitumor agent for breast cancer treatment. However, the side-effects of ABEM are unclear in the liver. This study investigated the protective effect of curcumin (CURC) on liver damage caused by ABEM. The rats were divided into five groups with eight animals in each group; Control, DMSO (150 µL for per rats), CURC, 30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CURC (26 mg/kg/day ABE, 30 mg/kg/day) groups. Injections were administered daily for 28 days. The levels of AST, LDH, HDL, LDL, triglyceride, and total cholesterol in serum, and hepatic tissue fibrosis, caspase-3, Bax, and TNF-α expression were higher in the ABE group compared to the control group (p < 0.05). Also, these parameters in the ABEM + CURC group were lower than in the ABE group (p < 0.05). The results showed that ABE administration could cause liver damage and increase fibrosis in the liver. In addition, it was shown that co-administration of CURC with ABE could suppress the levels of AST, LDH, HDL, LDL, triglyceride, and total cholesterol in serum, and fibrosis, caspase-3, Bax, and TNF-α expressions in the liver. These data are the first in the literature. Therefore, the administration of CURC following ABE may be a therapeutic agent in preventing liver damage.

The protective effect of curcumin on cardiac markers and fibrosis in abemaciclib-induced cardiac damage in rats.

Abemaciclib (ABE) is a cyclin-dependent kinase inhibitor used in combination with an antiestrogen in the treatment of breast cancer. In addition to the important therapeutic properties of this drug, its side effects are not fully known. In this study, we aimed to investigate the protective effect of curcumin (CUR) on cardiac damage caused by ABE administration. Forty rats were equally divided into control, dimethyl sulfoxide (150 µL), CUR (30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CUR (26 mg/kg/day ABE and 30mg/kg/day CUR) groups (n = 8). Injections were administered daily for 28 days. Troponin-I, total cholesterol, and creatine kinase myocardial band (CK-MB) levels and cardiac fibrosis were higher in the ABE group than in the control group (p < 0.05), and were lower in the ABE + CUR group than in the ABE group (p < 0.05). The results showed that ABE administration can cause cardiac damage and increase cardiac fibrosis. However, they showed that coadministration of CUR with ABE could suppress increases in CK-MB, troponin-I, and total cholesterol levels and also cardiac fibrosis associated with cardiac damage. Therefore, we can infer that the subsequent administration of CUR ABE treatment can be used as a therapeutic strategy for preventing cardiac damage.

Involvement of TRPM2 Channel on Doxorubicin-Induced Experimental Cardiotoxicity Model: Protective Role of Selenium.

Doxorubicin (DOXR) is an important chemotherapeutic drug used in cancer treatment for many years. Several studies reported that the use of DOXR increased toxicity by causing an increase in oxidative stress (OS), especially in the heart. In this study, we investigated the protective effect of selenium (Se) and the role of transient receptor potential melastatin-2 (TRPM2) channel activation by using N-(p-amylcinnamoyl) anthranilic acid (ACA) in a model of DOXR-induced cardiotoxicity. Sixty female rats were equally divided into the control, dimethyl sulfoxide (DMSO), DOXR, DOXR + Se, DOXR + ACA, and DOXR + Se + ACA groups. Glutathione (GSH), glutathione peroxidase (GSH-Px), caspases (Cas) 3 and 9, interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), poly [ADP-ribose] polymerase 1 (PARP-1), and TRPM2 channel levels were measured by ELISA. In addition, histopathological examination was performed in cardiac tissues and TNF-α, caspase 3, and TRPM2 channel expression levels were determined immunohistochemically. The levels of GSH, GSH-Px, caspases 3 and 9, IL-1ß, TNF-α, ROS, PARP-1, and TRPM2 channel in serum, and cardiac tissue in the DOXR group were higher than in the control and DMSO groups (p < 0.05). However, these parameters in Se and/or ACA treatment groups were lower than in the DOXR group (p < 0.05). Also, we determined that Se and/or ACA treatment together with DOXR application decreased the TNF-α, Cas-3, and TRPM2 channel expression levels in the cardiac tissue. The data showed that administration of Se and/or ACA treatment together with DOXR may be used as a therapeutic agent in preventing DOXR-induced cardiotoxicity.

Evaluation of repeated ghrelin administration on seizures, oxidative stress and neurochemical parameters in pentyleneterazole induced kindling in rats.

Introduction: Epileptic seizures are thought to be caused by the impaired balance between excitatory (glutamate) and inhibitor [gamma amino butyric acid (GABA)] neurotransmitters in the brain. Neuropeptides have potent modulator properties on these neurotransmitters.Objective: Ghrelin exerts anticonvulsant effects in an acute pentylenetetrazole (PTZ) model. However, the effect of repeated ghrelin injections in chronic pentylenetetrazole kindling model is not known. In this study, the effects of repeated ghrelin administration on seizure scores, working memory, locomotor activity, oxidative biomarkers, and neurochemical parameters in PTZ kindling in rats was examined.Methods: For this purpose, 35 mg/kg of PTZ was administered intraperitoneally to the experimental groups. The rats also received physiological saline/diazepam or ghrelin before each PTZ injection. After behavioural analysis (Y-maze, rotarod, and locomotor activity tests), biochemical and neurochemical analyses were conducted using ELISA.Results: PTZ administration induced progression in the seizure scores and all of the rats in the PS + PTZ group were kindled with the 20th injection. Ghrelin treatment significantly reduced the seizure scores. The difference among the groups in terms of the Y-maze, locomotor activity, and rotarod tests was nonsignificant. PTZ administration significantly decreased the brain GABA, CAT, and AChE levels, and increased the MDA, NO, and protein carbonyl levels. Repeated ghrelin treatment ameliorated the GABA, AChE, CAT, MDA, NO, and protein carbonyl levels.Conclusion: Taken together, the results indicated that repeated ghrelin treatment had antioxidant, and anticonvulsant activity on PTZ kindling in rats.

The synergistic effects of testosterone and phophodiesterase-5 inhibitor combination on oxidative stress markers, matrix metalloproteinases and oxidative DNA damage: A randomized controlled experimental study / Efecto sinérgico del uso combinado de testosterona y el inhibidor de fosfodiesterasa en los marcadores del estrés oxidativo, metaloproteinasas de la matriz y daño oxidativo del AND: estudio experimental contolado y aleatorizado

Purpose: To investigate the effects of combined tadalafil and testosterone usage on oxidative stress, DNA damage and MMPs in testosterone deficiency.Methods: Fifty rats were randomly divided into 5 groups (group-1: sham group-placebo, group-2: bilateral orchiectomy (ORX), group-3: bilateral ORX+tadalafil, group-4: bilateral ORX+testosterone, group-5: bilateral ORX+tadalafil+testosterone). Group-3 received tadalafil (5mg/kg/day, oral). Group-4 was administered testosterone undecanoate (100mg/kg i.m., single dose). Group-5 was administered a combination of tadalafil and testosterone undecanoate. All groups were compared with regard to serum nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX-4), total thiol, matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels.Results: Total thiol levels of group-2 were significantly lower than the other groups and thiol levels were higher in group-1 and group-5 than in the other groups. NOX4, MMP2 and 9 levels in group-2 were higher than in the other groups. MMP-9 levels in group-5 were lower than in groups 3 and 4 (p=.001). The level of 8-OHdG in groups 2 and 3 was higher than in the other groups (p=.001). In correlation analysis, 8-OHdG, MMP2, and 9 levels were negatively correlated with total thiol, whereas NOX4 and 8-OHdG levels were positively correlated with MMPs values.Conclusions: The combination of testosterone with PDE-5 inhibitor suppresses MMP-9 levels and increases total thiol levels better than testosterone alone and tadalafil alone. Therefore, testosterone can be considered for use with PDE-5 inhibitor from the initial stage in case of testosterone deficiency. (AU)

Objetivo: Investigar los efectos del uso combinado de tadalafil y testosterona en cuanto a estrés oxidativo, daño del ADN y metaloproteinasas de la matriz (MMPs) en la deficiencia de testosterona.Métodos: Se dividió aleatoriamente a cincuenta ratas en cinco grupos (grupo-1: grupo de simulación-placebo, grupo-2: orquiectomía bilateral (ORX), grupo-3: ORX bilateral+tadalafil, grupo-4: ORX bilateral+testosterona, grupo-5: ORX bilateral+tadalafil+testosterona). El grupo 3 recibió tadalafil (5mg/kg/day, oral). El Grupo 4 recibió undecanoato de testosterona (100mg/kg i.m, dosis única). El Grupo 5 recibió una combinación de tadalafil y undecanoato de testosterona. Se comparó a todos los grupos con respecto a los niveles séricos de nicotinamida adenina dinucleótido fosfato oxidasa-4 (NOX-4), tiol total, metaloproteinasa de la matriz 2 (MMP-2), MMP-3 y MMP-9, inhibidor tisular de metaloproteinasas-1 (TIMP-1) y TIMP-2, y 8-hidroxi-2-deoxi guanosina (8-OHdG).Resultados: Los niveles totales de tiol del grupo 2 fueron significativamente menores que en el resto de grupos, y los niveles de tiol fueron mayores del grupo 1 y el grupo 5 con respecto a los demás grupos. Los niveles de NOX4, MMP2 y 9 en el grupo 2 fueron mayores que los del resto de grupos. Los niveles de MMP-9 del grupo 5 fueron menores que los de los grupos 3 y 4 (p=0,001). El nivel de 8-OHdG de los grupos 2 y 3 fue mayor que los del resto de grupos (p=0,001). En el análisis de correlación, los niveles de 8-OHdG, MMP2, y 9 guardaron una correlación negativa con tiol total, mientras que los niveles de NOX4 y 8-OHdG se correlacionaron positivamente con los valores de MMPs.Conclusiones: La combinación de testosteronay el inhibidor de PDE-5 suprime los niveles de MMP-9 e incrementa los niveles totales de tiol, de mejor manera que testosterona y tadalafilen solitario. Por tanto, puede considerarse el uso de testosterona con el inhibidor de PDE-5 en las etapas iniciales de deficiencia de testosterona. (AU)

The synergistic effects of testosterone and phophodiesterase-5 inhibitor combination on oxidative stress markers, matrix metalloproteinases and oxidative DNA damage: A randomized controlled experimental study.

PURPOSE: To investigate the effects of combined tadalafil and testosterone usage on oxidative stress, DNA damage and MMPs in testosterone deficiency. METHODS: Fifty rats were randomly divided into 5 groups (group-1: sham group-placebo, group-2: bilateral orchiectomy (ORX), group-3: bilateral ORX+tadalafil, group-4: bilateral ORX+testosterone, group-5: bilateral ORX+tadalafil+testosterone). Group-3 received tadalafil (5mg/kg/day, oral). Group-4 was administered testosterone undecanoate (100mg/kg i.m., single dose). Group-5 was administered a combination of tadalafil and testosterone undecanoate. All groups were compared with regard to serum nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX-4), total thiol, matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels. RESULTS: Total thiol levels of group-2 were significantly lower than the other groups and thiol levels were higher in group-1 and group-5 than in the other groups. NOX4, MMP2 and 9 levels in group-2 were higher than in the other groups. MMP-9 levels in group-5 were lower than in groups 3 and 4 (p=.001). The level of 8-OHdG in groups 2 and 3 was higher than in the other groups (p=.001). In correlation analysis, 8-OHdG, MMP2, and 9 levels were negatively correlated with total thiol, whereas NOX4 and 8-OHdG levels were positively correlated with MMPs values. CONCLUSIONS: The combination of testosterone with PDE-5 inhibitor suppresses MMP-9 levels and increases total thiol levels better than testosterone alone and tadalafil alone. Therefore, testosterone can be considered for use with PDE-5 inhibitor from the initial stage in case of testosterone deficiency.

What is the impact and efficacy of routine immunological, biochemical and hematological biomarkers as predictors of COVID-19 mortality?

It remains important to investigate the changing and impact of routine blood values (RBVs) in order to predict mortality and follow an appropriate treatment in COVID-19 patients. In the study, the importance of RBVs in the mortality of patients with COVID-19 was investigated. The changes in the biochemical, hematological, and immunological parameters of patients who recovered (n = 4364) and died (n = 233) from COVID-19 over time and their relationship with the mortality of the disease were evaluated retrospectively. Odds ratios of the parameters affecting one-month mortality were calculated by running multiple-logistic-regression analysis. The cut off values and diagnostic efficiencies of the parameters that posed a risk for mortality were obtained via receiver operating curve analysis. It was determined that the C-reactive protein (CRP), D-dimer, procalcitonin, erythrocyte-sedimentation-rate (ESR), troponin values were at abnormal levels until death occurred in the patients who died. In addition, the procalcitonin levels were consistently high in patients who died. The patients who died generally had a sustained increase in their leukocyte and neutrophil levels and biochemical variables, and an ongoing decrease in lymphopenia and eosinopenia levels. Although significant changes were observed in liver function tests, cardiac troponin, hemogram values, kidney function tests and parameters related to inflammation in deceased patients, high ESR, international-normalized-ratio (INR), prothrombin-time (PT), CRP, D-dimer, ferritin and red-cell-distribution width (RDW) values, respectively, were the most effective predictive mortality risk biomarkers of COVID-19. In addition, neutrophilia, leukocytosis, thrombocytopenia, erythrocytopenia were other risk predictors of mortality. Indicators was found in this study can be successfully used to predict mortality from COVID-19.

Can zaprinast and avanafil induce the levels of angiogenesis, bone morphogenic protein 2, 4 and 7 in kidney of ovariectomised rats?

OBJECTIVE: This study investigated effects of zaprinast and avanafil on angiogenesis, vascular endothelial growth factor (VEGF), bone morphogenic protein (BMP) 2, 4 and 7. METHODS: Female rats were randomly divided into four groups (n = 6). Sham; abdomen was approximately 2 cm opened and closed. Ovariectomised (OVX); abdomen was opened 2 cm and the ovaries were cut. OVX + zaprinast and OVX + avanafil groups; after the same procedure with OVX, 10 mg/kg zaprinast and avanafil were orally administered for 2 month, respectively. Angiogenesis and the levels of VEGF, BMP2, 4 and 7 were determined. RESULTS: VEGF, BMP2, 4 and 7 levels in OVX + zaprinast and especially OVX + avanafil groups were higher than the sham and OVX (p < .05). However, only VEGF and BMP2 levels in OVX + zaprinast group were significant according to sham (p < .05). Also, angiogenesis in OVX + zaprinast and OVX + avanafil groups was dominant according to sham and OVX (p < .05). CONCLUSIONS: Zaprinast and avanafil induced BMP2, 4 and 7 levels synergistically with increased VEGF and angiogenesis in renal tissue.

Stimulating effects of vardenafil, tadalafil, and udenafil on vascular endothelial growth factor, angiogenesis, vitamin D3, bone morphogenic proteins in ovariectomized rats.

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), VitaminD3, BMP2 and 4 levels in rat's kidney. RESULTS: VEGF, BMP2 and 4, VitaminD3, 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 VitaminD3 levels.

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.

Objective: This study investigated effect of zaprinast and avanafil on vascular endothelial growth factor (VEGF), bone morphogenic protein (BMP) 4 and 7, and vitamin D3 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 µg/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. VitaminD3, 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 D3, BMP4 and 7 levels by increasing angiogenesis in renal.