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The protective effects of caffeic acid phenethyl ester in isoniazid and ethambutol-induced ocular toxicity of rats

Abstract Purpose: This study intended to examine the effect of caffeic acid phenethyl ester (CAPE) on isoniazid (INH) and/or ethambutol (ETM)-induced retina and optic nerve toxicity in a rat model. Methods: This study included eight groups, each containing 10 rats. The groups were Control, INH, ETM, CAPE, INH+CAPE, ETM+CAPE, INH+ETM and INH+ETM+CAPE. Rats were given orally 50 mg/kg/d of INH and 50 mg/kg/d of ETM in tap water for 30 d. 10 μmol/kg of CAPE were intraperitoneally injected for 30 d. The first dose of CAPE was given 24 h before the INH and ETM treatment and continued until sacrifice. Control group was given only tap water for 30 d. Rats were anaesthetized and sacrificed on the 30th day of experiment. Superoxide dismutase (SOD) activities, malondialdehyde (MDA), total anti-oxidant status (TAS), total oxidant status (TOS) were measured on the dissected and excised retina and optic nerve samples. Fellow eyes were used for histopathologic evaluation and the retinal ganglion cell (RGC) count. In addition, CAPE, INH and ETM interaction with SOD isoforms were calculated in silico. Results: The SOD activity and TAS levels were found significantly higher in CAPE-treated groups compared to INH and/or ETM-treated groups (p < 0.0001). But the MDA, and TOS levels were significantly lower in CAPE-treated groups (p < 0.0001). The mean RGC count is significantly decreased in INH, ETM and INH+ETM groups compared with INH+CAPE, ETM+CAPE and INH+ETM+CAPE groups, respectively (p values 0.001, 0.042, and 0.001 respectively). Besides, in silico calculations showed that binding affinity of CAPE to SOD isotypes was higher than that of INH and ETM. Conclusion: This study demonstrates that CAPE treatment may decrease the oxidative stress in the retina and optic nerve of INH- and ETM-treated rats and may prevent RGC loss. As an underlying mechanism, CAPE and SOD interaction seems crucial for alleviation of ocular oxidative stress and RGCs toxicity.

The protective effects of pomegranate extracts against renal ischemia-reperfusion injury in male rats.

Aim: To evaluate the possible protective effect of pomegranate extract (PE) on rats following renal ischemia–reperfusion (I/R) injury. Materials and Methods: Twenty-four Wistar rats were divided into three groups. Sham group underwent laparotomy then waited for 45 minutes without ischemia. I/R group were subjected to left renal ischemia for 45 minutes followed by 60 minutes of reperfusion. I/R + PE group were subjected to the same renal I/R as the I/R group were also given 225 mg/kg PE peroral 30 minutes prior to the ischemia. Malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) were determined on the blood samples and kidney tissues. Histopathological analyses were conducted on the kidney tissues. Results: Serum TAC levels were significantly decreased in I/R group when compared with S group (P = 0.001). Serum MDA levels were increased in I/R group; however, it was not statistically significant. In rat kidney tissues, TOS levels and OSI index were significantly increased after I/R injury, while TAC levels were decreased. In I/R + PE group, PE reversed the negative effects of I/R injury. PE pretreatment was effective in decreasing tubular necrosis score. Conclusion: PE pretreatment ameliorated the oxidative damage and histopathological changes occurring following renal I/R injury.

Is montelukast as effective as N-acetylcysteine in hepatic injury due to acetaminophen intoxication in rats?

This study aims to investigate the acute protective effect of montelukast sodium in hepatic injury secondary to acetaminophen (APAP) intoxication. This study used 60 rats. The rats were grouped into 6 groups. The control group was administered oral distilled water 10 ml/kg, the APAP group oral APAP 1 g/kg, the montelukast sodium (MK) group oral MK 30 mg/kg, the acetaminophen+N-acetylcysteine (APAP+NAC) group oral APAP 1 g/kg, followed by a single dose of intraperitoneal NAC 1.5 g/kg three hours later, the acetaminophen+montelukast sodium (APAP+MK) group oral APAP 1 g/kg, followed by oral MK 30 mg/kg 3 h later, the acetaminophen+N-acetylcysteine+montelukast sodium (APAP+NAC+MK) group oral APAP 1 g/kg, followed by a single intraperitoneal NAC 1.5 g/kg plus oral MK 30 mg/kg 3 h later. Blood and liver tissue samples were taken 24h after drug administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin were studied from the blood samples. Liver tissue samples were used for histopathological examination. Compared with the control group, serum AST and ALT activities were higher in the APAP and APAP+NAC groups. APAP+NAC, APAP+MK, and APAP+NAC+MK groups had reduced serum ALT and AST activities than the group administered APAP alone. APAP+MK and APAP+NAC+MK groups had a lower serum ALP activity than the control group. Histopathologically, there was a difference between the group administered APAP alone and the APAP+MK and APAP+NAC+MK groups. MK is as protective as NAC in liver tissue in APAP intoxication in rats.

Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats

Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE.

Topical and subconjunctival ranibizumab (lucentis) for corneal neovascularization in experimental rat model

Abstract Purpose: To compare the effectiveness of the topical and subconjunctival (SC) ranibizumab treatment in experimental corneal neovascularization (NV) model in rats. Methods: A model of NV was generated by cauterizing right corneas of 30 Sprague-Dawley rats with silver nitrate. The animals were separated into five groups randomly. first group (control group) received topical artificial tear drops two times daily while second and third groups received topical ranibizumab four times daily at concentrations of 5 mg/mL and 10 mg/mL, respectively. Forth and fifth groups were given 0.5 mg/0.05 mL and 1 mg/0.1 mL of SC ranibizumab in the 1st, 3rd and 7th days. The measurements (percentage of NV area and number of vessels) from digital photographs of the corneas were determined and analyzed using analysis software (ImageJ, v1.38). The animals were sacrificed on the 10th day and their corneas were subjected to hemotoxylin-eosin histopathological staining and antisera against CD34 and von-Willebrand factor to evaluate microvascular structures immunohistochemically. Results: The percentage of the corneal NV area and number of vessels in all treatment groups was found to be significantly lower than the control group. There was no significant difference in relation to the percentage of NV area and number of vessels in the treatment groups. Score of the corneal edema was determined to be significantly less in the groups that undertook treatment. Number of vessels and inflammatory cells were significantly lower in the histological and immunohistochemical sections in the treated groups than in the control group. In all treatment groups, fibroblast intensity was significantly lower than the control group (p = 0.005). Conclusion: Topical or SC administration of ranibizumab seems to be a promising and effective medication in the treatment of corneal NV. Further research is recommended to assess the potential side effects and effective dose.

The Role of Apparent Diffusion Coefficient Quantification in Differentiating Benign and Malignant Renal Masses by 3 Tesla Magnetic Resonance Imaging.

BACKGROUND Diffusion-weighted magnetic resonance imaging (DWI) is a widely-accepted diagnostic modality whose efficacy has been investigated by numerous past studies in the differentiation of malignant lesions from benign entities. AIMS The aim of this study was to evaluate the efficiency of diffusion-weighted magnetic resonance imaging in the characterization of renal lesions. STUDY DESIGN Diagnostic accuracy study. METHODS A total of 137 patients with renal lesions were included in this study. The median apparent diffusion coefficient (ADC) values as well as the b 800 and b 1600 signal intensities of normal kidneys, solid components of mixed renal masses, and total cystic lesions were evaluated. RESULTS There were significant differences between the ADC values of lesions and normal renal parenchyma, and between the ADC values of benign and malignant renal lesions on DWIs at b values of 800 and 1600 s/mm(2) (p<0.001 and p<0.001, respectively). There were significant differences between the ADC values of Bosniak Category 1 and 2 cysts and the ADC values of Bosniak Category 1 and 3 cysts on DWIs at b values of 800 s/mm(2) (p<0.001) and 1600 s/mm(2) (p<0.001). A cutoff value of 1.902 × 10(-3) mm(2)/s for the ADC with a b value of 800 s/mm(2) provided 88% sensitivity and 96% specificity for differentiation between benign and malignant renal lesions. A cutoff value of 1.623 × 10(-3) mm(2)/s for the ADC with a b value of 1600 s/mm(2) provided 79% sensitivity and 96% specificity (p<0.001) for the differentiation between benign and malignant renal lesions. CONCLUSION Accurate assessment of renal masses is important for determining the necessity for surgical intervention. DWI provides additional value by differentiating benign from malignant renal tumors and can be added to routine kidney MRI protocols.

Nebivolol Ameliorates Hepatic Ischemia/Reperfusion Injury on Liver But Not on Distant Organs

ABSTRACT Introduction: Hepatic ischemia/reperfusion injury may occur after large tumor resection and liver transplantation procedures. Nitric oxide was shown to have protective effects on ischemia/reperfusion injury. Nebivolol is a compound that has been reported to improve nitric oxide release. We evaluated the effects of nebivolol in a rat liver ischemia/reperfusion model. Methods: A total of 40 rats were randomly divided into four groups (n = 10 each). Group I underwent only laparotomy, Group II was administered nebivolol and then underwent laparotomy, Group III underwent laparotomy and hepatic ischemia/reperfusion, and Group IV was administered nebivolol and then underwent laparotomy and hepatic ischemia/reperfusion. Serum AST, ALT, urea, and creatinine levels, and TAS and TOS levels of liver, lung, and kidney tissues were determined. Histopathological determination was also performed. Results: Nebivolol significantly reduced liver function tests in group IV, but it did not improve renal functions. Oxidative stress and abnormal histopathological findings were found to be reduced in liver tissue in group IV. Although the oxidative stress was increased after hepatic ischemia/reperfusion, nebivolol could not reduce the oxidative stress in kidney tissue. There were no significant differences between group III and group IV in terms of the histopathological changes in kidney tissue. There were no significant differences in lung tissue between the groups. Conclusions: The results of this study suggest that nebivolol has protective effects on liver but not on distant organs in a hepatic ischemia/reperfusion injury model. These experimental findings indicate that nebivolol may be useful in the treatment of hepatic ischemia/reperfusion injury.

The effects of caffeic acid phenethyl ester in acute methanol toxicity on rat retina and optic nerve

Abstract Purpose: We aimed to test caffeic acid phenethyl ester (CAPE) as an antidote for acute methanol (MeOH) toxicity and to compare it with ethanol. Methods: This study included five groups, each containing eight rats. The groups were control, methotrexate (MTX), MeOH, ethanol and CAPE. All rats except control group were treated with intraperitoneal (i.p.) MTX (0.3 mg/kg/d) for 7 d. At the 8th day of the experiment, i.p. injection of MeOH (3 g/kg) was administered in MeOH, ethanol and CAPE groups. Four hours after MeOH treatment, 0.5 g/kg ethanol was injected i.p. in ethanol group; 10 μmol/kg CAPE i.p. in CAPE group; serum physiologic i.p. in other groups. After 8 h, rats were anaesthetized and sacrificed. Total anti-oxidant status (TAS), total oxidant status (TOS) were measured on the dissected and excised retina and optic nerve samples. Fellow eyes were used for histopathologic evaluation and the cell count of retinal ganglion cell (RGC) layer. In addition, interactions of alcohol dehydrogenase with CAPE, ethanol, MeOH and pyrazole derivatives were investigated. Results: Either CAPE or ethanol co-treatment decreased the TOS levels and increased the TAS levels compared to the MeOH group. MeOH treatment decreased the mean cell count in RGC layer. CAPE co-treatment significantly prevented cell loss (p = 0.040). Besides, in silico calculations showed that binding affinity of CAPE to alcohol dehydrogenase was higher than those of MeOH, ethanol, and pyrazole derivatives were. Conclusion: This study demonstrated that CAPE treatment decreased the oxidative stress in acute MeOH intoxication in the retina and optic nerve; beside that, protected RGC layer histology. In silico, CAPE had higher affinity score than MeOH, ethanol, pyrazole and pyrazole derivatives in the case of interaction with alcohol dehydrogenase.

CAFFEIC ACID PHENETHYL ESTER PROTECTS KIDNEYS AGAINST ACETYLSALICYLIC ACID TOXICITY IN RATS

Aim: The aim of this study was to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on acetylsalicylic acid (ASA)-induced renal damage in rats. Materials and methods: A total of 40 rats were randomly divided into five groups, with eight rats in each group—group 1: control, not receiving any medication; group 2: ASA (50 mg/kg/day); group 3: ASA (50 mg/kg/day) + CAPE (20 μg/kg/day); group 4: ASA (100 mg/kg/day); and group 5: ASA (100 mg/kg/day) + CAPE (20 μg/kg/day). ASA and CAPE were given via orogastric gavage for 5 days. The total oxidant status (TOS), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) activity of the blood samples and kidney tissues were determined. Histopathological examinations of the kidneys were performed using light microscopic methods. Results: The TOS level in the serum of rats and kidney tissues given ASA (groups 2 and 4) significantly increased, but the levels of TAC and PON-1 in these tissues significantly decreased in group 4 when compared with the control rats (p < 0.05). The levels of TAC and PON-1 in the kidney tissues increased and the levels of TOS decreased in the CAPE treatment groups (groups 3 and 5) when compared with the rats in the no CAPE treatment groups (groups 2 and 4). The PON-1, TAC, and TOS values reverted to normal levels in group 5 when compared to group 4 (p < 0.05). These results were supported by histopathological observation. Conclusion: Oxidative stress plays an important role in ASA-induced nephrotoxicity, and CAPE may protect against ASA-induced nephrotoxicity in rats.

Urothelial neoplasm of the bladder in childhood and adolescence: a rare disease

ABSTRACT Purpose: Bladder tumors are rare in children and adolescents. For this reason, the diagnosis is sometimes delayed in pediatric patients. We aimed to describe the diagnosis, treatment, and follow-up methods of bladder urothelial neoplasms in children and adolescents. Materials and Methods: We carried out a retrospective multicenter study involving patients who were treated between 2008 and 2014. Eleven patients aged younger than 18 years were enrolled in the study. In all the patients, a bladder tumor was diagnosed using ultrasonography and was treated through transurethral resection of the bladder (TURBT). Results: Nine of the 11 patients (82%) were admitted with gross hematuria. The average delay in diagnosis was 3 months (range, 0–16 months) until the ultrasonographic diagnosis was performed from the first episodes of macroscopic hematuria. A single exophytic tumor (1–4cm) was present in each patient. The pathology of all patients was reported as superficial urothelial neoplasm: two with papilloma, one with papillary urothelial neoplasm of low malignant potential (PUNLMP), four with low grade pTa, and four with low grade pT1. No recurrence was observed during regular cystoscopic and ultrasonographic follow-up. Conclusions: Regardless of the presence of hematuria, bladder tumors in children are usually not considered because urothelial carcinoma in this population is extremely rare, which causes a delay in diagnosis. Fortunately, the disease has a good prognosis and recurrences are infrequent. Cystoscopy may be unnecessary in the follow-up of children with bladder tumors. We believe that ultrasonography is sufficient in follow-up.