Mustafa Sagir

The Protective Effects of Apocynin on Kidney Damage Caused by Renal Ischemia/Reperfusion

PURPOSE This experimental study was designed to explore the protective effect of apocynin, the NADPH-oxidase inhibitor, on kidney damage induced by ischemia/reperfusion (I/R) in a rat model. METHODS Thirty-two rats were randomly divided into a control group and three I/R groups (1-hour ischemia followed by 23-hour reperfusion). Three I/R groups were treated by apocynin (20 mg/kg, i.p.) at two different time points (before ischemia and during ischemia). The histopathological findings, including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GPX), reduced glutathione (GSH), myeloperoxidase (MPO), blood urea nitrogen (BUN), and serum creatinine (Cr) levels, were determined. RESULTS Kidney tissue MDA and MPO, and serum BUN and Cr levels were found to be significantly higher in the I/R group, but there was no statistically significant difference in the levels of SOD, CAT, GPX, and GSH between the I/R and the control groups. Although apocynin significantly reduced MDA and MPO in group 3 and increased GPX in both treatment groups when compared to the I/R group, the elevated BUN and Cr levels were significantly reduced in treatment groups. Renal I/R injury also induced extensive tubular necrosis, glomerular damage, and apoptosis in the histological evaluation. Apocynin, especially when used during ischemia, ameliorated these histological damages in different amounts in treatment groups. CONCLUSION The beneficial effects of apocynin on renal I/R injury were evaluated for the first time.

Protective Effect of Dexpanthenol on Ischemia-Reperfusion-Induced Renal Injury in Rats

Background/Aims: This experimental study was designed to investigate protective and therapeutic effects of Dexpanthenol (Dxp), an alcoholic analogue of pantothenic acid, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Methods: Forty rats were randomly divided into a control group and 4 I/R groups (1 h ischemia followed by 23 h reperfusion). Three I/R groups were treated by Dxp (500 mg/kg, i.p.) at 3 different time points (before ischemia, during ischemia and late reperfusion). The histopathological findings including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) levels were determined. Results: Kidney tissue MDA levels were found to be significantly higher in the I/R group, whereas the values of GPX were lower when compared to the control group. The levels of SOD and CAT did not reach to statistical meaning level in I/R group. Dxp given during ischemia reduced the elevated MDA levels to the nearly control levels and this ameliorating effect was found as parallel to the result of GPX. Serum levels of BUN and Cr were significantly higher in I/R group. Dxp given during ischemia significantly reduced the elevated BUN and Cr levels when compared to I/R group. Renal I/R injury also induced extensive tubular necrosis, glomerular damage and apoptosis in the histological evaluation. Dxp ameliorated these histological damages in different amounts in all treatment groups. Conclusion: In this study the protective effects of Dxp against renal I/R injury has been evaluated for the first time.

Intravesical hyaluronic acid and chondroitin sulfate alone and in combination for urinary tract infection: Assessment of protective effects in a rat model

Objective:  To determine the protective effects of hyaluronic acid and chondroitin sulfate in treating urinary tract infections in a rat model.

Evaluation of the cardiovascular effects of varenicline in rats.

Background Cardiovascular disease is an important cause of morbidity and mortality among tobacco users. Varenicline is widely used worldwide to help smoking cessation, but some published studies have reported associated cardiovascular events. Objective To determine the cardiovascular toxicity induced by varenicline in rats. Materials and methods We randomly separated 34 rats into two groups: 1) the control group (given only distilled water orally, n=10) and the varenicline group (given 9 μg/kg/day varenicline on days 1–3, 9 μg/kg twice daily on days 4–7, and 18 μg/kg twice daily on days 8–90 [total 83 days], n=24). Each group was then subdivided equally into acute and chronic subgroups, and all rats in these groups were euthanized with anesthesia overdose on days 45 and 90, respectively. Body and heart weights, hemodynamic (mean oxygen saturation, mean blood pressure, and heart rate, electrocardiographic (PR, QRS, and QT intervals) biochemical (oxidants and antioxidants), and histopathological analyses (including immunostaining) were performed. Results Acute varenicline exposure resulted in loss of body weight, while chronic varenicline exposure caused heart weight loss and decreased mean blood pressure, induced lipid peroxidation, and reduced antioxidant activity. Both acute and chronic varenicline exposure caused impairment of mean oxygen saturation. QT interval was prolonged in the chronic varenicline group, while PR interval prolongation was statistically significant in both the control and acute varenicline groups. Caspase-9 activity was also significantly increased by chronic exposure. Moreover, histopathological observations revealed severe morphological heart damage in both groups. Conclusion Adverse effects of chronic varenicline exposure on cardiovascular tissue were confirmed by our electrocardiographic, biochemical, and histopathological analyses. This issue needs to be investigated with new experimental and clinical studies to evaluate the exact mechanism(s) of the detrimental effects of varenicline. Physicians should bear in mind the toxic effects of varenicline on the cardiovascular system when prescribing it for smoking cessation.

The Effect of Sildenafil on Recuperation from Sciatic Nerve Injury in Rats

BACKGROUND Severe functional and anatomical defects can be detected after the peripheral nerve injury. Pharmacological approaches are preferred rather than surgical treatment in the treatment of nerve injuries. AIMS The aim of this study is to perform histopathological, functional and bone densitometry examinations of the effects of sildenafil on nerve regeneration in a rat model of peripheral nerve crush injury. STUDY DESIGN Animal experiment. METHODS The study included a total of thirty adult Sprague-Dawley rats that were divided into three groups of ten rats each. In all rats, a crush injury was created by clamping the right sciatic nerve for one minute. One day before the procedure, rats in group 1 were started on a 28-day treatment consisting of a daily dose of 20 mg/kg body weight sildenafil citrate given orally via a nasogastric tube, while the rats in group 2 were started on an every-other-day dose of 10 mg/kg body weight sildenafil citrate. Rats from group 3 were not administered any drugs. Forty-two days after the nerve damage was created, functional and histopathological examination of both sciatic nerves and bone densitometric evaluation of the extremities were conducted. RESULTS During the rotarod test, rats from group 3 spent the least amount of time on the rod compared to the drug treatment groups at speeds of 20 rpm, 30 rpm and 40 rpm. In addition, the duration for which each animal could stay on the rod throughout the accelerod test significantly reduced in rats from group 3 compared to rats from groups 1 and 2 in the 4-min test. For the hot-plate latency time, there were no differences among the groups in either the basal level or after sciatic nerve injury. Moreover, there was no significant difference between the groups in terms of the static sciatic index (SSI) on the 42(nd) day (p=0.147). The amplitude was better evaluated in group 1 compared to the other two groups (p<0.05). Under microscopic evaluation, we observed the greatest amount of nerve regeneration in group 1 and the lowest in group 3. However, this difference was not statistically significant. Moreover, there was no significant difference in the bone mineral density (BMD) levels among the groups. CONCLUSION We believe that a daily single dose of sildenafil plays an important role in the treatment of sciatic nerve damage and bone healing and thus can be used as supportive clinical treatment.

Protective effects of melatonin against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cardiac injury in rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the prototype of a group of highly toxic environmental chemicals. Although there are some suggestions regarding TCDD-induced cardio-toxicity, the exact mechanisms underlying this process have not been fully discovered. One mechanism related to this toxicity is believed to be the generation of reactive oxygen species. Melatonin is known to be a strong antioxidant and has a free radical scavenging ability. Therefore, the aim of this study was to investigate the TCDD-induced cardio-toxicity and the protective effects of melatonin in rats. Rats were randomly divided into 4 equal groups (n=7 for each group). Group 1 was control; group 2 was TCDD group (2µg/kg/week, p.o); group 3 was melatonin group (5mg/kg/day, i.p.) and group 4 was TCDD and melatonin treatment group. All agents were continued to be administered until the 45th day. Body/heart weights, mean oxygen saturation (PO2%), hemodynamic [mean blood pressure (MBP) and heart rate (HR) from the cannulated-carotid artery] and electrocardiographic evaluations (arrhythmias and duration of PR, QRS and QT intervals), biochemical and histopathological analysis were carried out. TCDD exposure caused significant body and heart weight loss, impairment of PO2%, and decrease of MBP and HR levels. Also, major ECG changes and prolongation of PR, QRS and QT durations were observed in TCDD-exposed rats. In biochemical analysis, TCDD significantly induced lipid peroxidation and reduced antioxidant activities. Moreover, our histopathological observations were in accordance with the biochemical results. According to the results, melatonin treatment significantly protected the subjects from TCDD-induced cardio-toxicity.

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801

Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.