Türker Çavuşoğlu

Exenatide reduces TNF-α expression and improves hippocampal neuron numbers and memory in streptozotocin treated rats.

Recent studies suggest a possible link between type 2 diabetes and Alzheimers disease (AD). Glucogan-like peptide 1 (GLP-1) facilitates insulin release from pancreas under hyperglycemic conditions. In addition to its metabolic effects, GLP-1 and its long-lasting analogs, including exenatide can stimulate neurogenesis and improve cognition in rodent AD model. The aim of the present study was to investigate the effects of exenatide on hippocampal cellularity, cognitive performance and inflammation response in a rat model of AD. Fourteen rats were used to create AD model using intracerebroventricular (ICV) streptozotocin (STZ) infusion while 7 rats were administered 0.9% NaCl only (sham-operated group). Following stereotaxic surgery, STZ received rats were randomly distributed into two groups, and treated with either saline or exenatide 20 µgr/kg/day through intraperitoneally for two weeks. Then, cognitive performance (passive avoidance learning), brain tumor necrosis factor alpha (TNF-α) levels, choline acetyltransferase (ChAT) activity and hippocampal neuronal count were determined. While the brain TNF-α levels were significantly high in the saline-treated STZ group, exenatide treatment suppressed the increase in TNF-α levels. Saline-treated STZ group showed reduced ChAT activity compared to sham group. However, exenatide significantly preserved brain ChAT activity. The cognitive performance was also impaired in saline group while exenatide improved memory in rats. Moreover, exenatide treatment significantly prevented the decrease in hippocampal neurons. Overall, the results of the present study clearly indicated exenatide might have beneficial effects on impaired cognitive performance and hippocampal neuronal viability in AD by suppressing the inflammation response and increasing cholinergic activity.

The neuroprotective effect of erythropoietin on experimental Parkinson model in rats.

Dopaminergic neuronal loss in Parkinsons disease (PD) results from oxidative stress, neuroinflammation and excitotoxicity. Because erythropoietin (EPO) has been shown to have antioxidant, anti-inflammatory and neuroprotective effects in many previous studies, present study was designed to evaluate the effect of EPO on rotenone-induced dopaminergic neuronal loss. The rats in which PD was induced by stereotaxical infusion of rotenone showed increased MDA and TNF-alpha levels and decreased HVA levels. On the other hand, EPO treatment resulted in markedly decreased MDA and TNF-alpha levels and increased HVA levels. EPO treatment in rotenone-infusion group resulted in improvement of striatal neurodegeneration and a significant increase in decreased total number of neurons and immunohistochemical TH positive neurons. Results of the present study demonstrate the neuroprotective, anti-inflammatory and antioxidant effects of EPO in a rotenone-induced neurodegenerative animal model.

Comparison of nephron-protective effects of enalapril and GLP analogues (exenatide) in diabetic nephropathy.

BACKGROUND One of the major concerns is a nephropathy in diabetes, which applies many different kinds of medicines. However, required level of the treatment of renal disease has not been achieved. AIM To investigate and compare the effect of the enalapril and the exenatide on diabetic nephropathy in rats developed diabetes by streptozosin. MATERIAL AND METHODS 32 male Sprague Dawley rats were divided into 4 groups: (1) Control, (2) Diabetic (DM), (3) DM+ Enalapril, and (4) DM+ exenatide groups. Then, the animals were euthanized and their blood samples were collected by cardiac puncture for blood glucose; blood urea nitrogen (BUN), creatinin, and nephrectomy were performed for histopathologic examination, and urine samples were taken on stick for proteinuria. RESULTS Administration of the enalapril or the exenatide in diabetic rats resulted in a significant reduction both fibronectin, induced nitric oxide synthase (i-NOS) expression in glomerular area and urine protein levels. It was shown that both of enalapril and exenatide protected the renal glomerulus more than diabetic group in the nephropathy histopathologically. CONCLUSION The beneficial effects of enalapril and exenatide which reduces fibronectin, i-NOS expression and urine protein levels or increases recovery of glomerules, might be used for preventing the harmful effects of diabetic nephropathy.

Effect of taurine on rat Achilles tendon healing

Abstract Taurine has anti-inflammatory and antioxidant characteristics. We have introduced taurine into a tendon-healing model to evaluate its effects on tendon healing and adhesion formation. Two groups of 16 rats underwent diversion and repair of the Achilles tendon. One group received a taurine injection (200 mg/ml) at the repair site, while the other group received 1 ml of saline. Specimens were harvested at 6 weeks and underwent biomechanical and histological evaluation. No tendon ruptured. Average maximum load was significantly greater in the taurine-applied group compared with the control group (p < 0.05). Similarly, average energy uptake was significantly higher in the taurine-applied group compared with the control group (p < 0.05). We observed no significant differences in stiffness in both groups (p > 0.05). After histological assessment, we found that fibroblast proliferation, edema, and inflammation statistically decreased in the treatment group (p < 0.05). These findings could indicate greater tendon strength with less adhesion formation, and taurine may have an effect on adhesion formation.

Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation

The cornea is the outermost tissue of the eye and it must be transparent for the maintenance of good visual function. The superficial epithelium of the cornea, which is renewed continuously by corneal stem cells, plays a critical role in the permanence of this transparency. These stem cells are localized at the cornea-conjunctival transition zone, referred to as the limbus. When this zone is affected/destroyed, limbal stem cell deficiency ensues. Loss of limbal stem cell function allows colonization of the corneal surface by conjunctival epithelium. Over 6 million people worldwide are affected by corneal blindness, and limbal stem cell deficiency is one of the main causes. Fortunately, it is becoming possible to recover vision by autologous transplantation of limbal cells obtained from the contralateral eye in unilateral cases. Due to the potential risks to the donor eye, only a small amount of tissue can be obtained, in which only 1-2% of the limbal epithelial cells are actually limbal stem cells. Vigorous attempts are being made to expand limbal stem cells in culture to preserve or even enrich the stem cell population. Ex vivo expanded limbal stem cell treatment in limbal stem cell deficiency was first reported in 1997. In the 20 years since, various protocols have been developed for the cultivation of limbal epithelial cells. It is still not clear which method promotes effective stem cell viability and this remains a subject of ongoing research. The most preferred technique for limbal cell culture is the explant culture model. In this approach, a small donor eye limbal biopsy is placed as an explant onto a biocompatible substrate (preferably human amniotic membrane) for expansion. The outgrowth (cultivated limbal epithelial cells) is then surgically transferred to the recipient eye. Due to changing regulations concerning cell-based therapy, the implementation of cultivated limbal epithelial transplantation in accordance with Good Laboratory Practice using xenobiotic-free systems is becoming widely accepted both in Turkey and worldwide.

Neuroprotective Effects of Eexenatide in a Rotenone-Induced Rat Model of Parkinson’s Disease☆

Backround: Several studies suggest an association between Parkinsons disease (PD) and type 2 diabetes mellitus; these 2 diseases are both known to affect the common molecular pathways. As a synthetic agonist for the glucagon‐like peptide 1 receptor, exenatide has been evaluated as a neuroprotective agent in multiple animal models. Rotenone models of PD have great potential for the investigation of PD pathology and motor and nonmotor symptoms, as well as the role of gene‐environment interactions in PD causation and pathogenesis. Therefore, in this study, the neurochemical, behavioral and histologic effects of exenatide on a rotenone‐induced rat model of PD were examined. Materials and Methods: Eighteen adult male rats were randomly divided into the following 3 groups (n = 6): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1) and the others received stereotaxical infusion of rotenone (groups 2 and 3). Apomorphine‐induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered exenatide for 28 days. Results: Malondialdehyde and tumor necrosis factor alpha levels increased in the rats with PD induced by rotenone, whereas malondialdehyde and tumor necrosis factor alpha levels markedly decreased in the rats treated with exenatide. The apomorphine‐induced rotation test scores of exenatide‐treated rats were determined to be lower compared with the untreated group. Additionally, treatment with exenatide significantly reduced the loss of dopaminergic neurons in striatum. Conclusions: These results have shown that exenatide has neuroprotective, anti‐inflammatory and antioxidant effects in a rotenone‐induced rat model of PD.

Neuroprotective effects of erythropoietin on Alzheimer’s dementia model in rats

BACKGROUND Although Alzheimers disease (AD) is the most common age-related neurodegenerative disease and characterized by memory impairment, only symptomatic treatments are available. OBJECTIVES Because recombinant human erythropoietin (rhEPO) has various neuroprotective effects and improves cognitive function in animal models of neurodegenerative disorders, we investigated the therapeutic effects of rhEPO in an intracerebroventricular (ICV)-streptozotocin (STZ) animal model of sporadic-AD. MATERIAL AND METHODS A total of 24 Sprague-Dawley adult rats were divided into 4 groups of naive control (n = 6), sham-operated (n = 6), ICV-STZ + saline (n = 6) and ICV-STZ + rhEPO (n = 6). Twelve rats with Alzheimers disease, induced by STZ injection (3 mg/kg) into both lateral ventricles using a stereotaxic frame (bilaterally ICV-STZ), were divided into 2 groups 5 days after the STZ injection: one treated with rhEPO 5000 (IU/kg/day, i.p.) and the other with 0.9% NaCl (1 mL/kg/day, i.p.) for 2 weeks. The sham-operated rats received bilaterally ICV-0.9% NaCl. No surgical operation or treatment was given to the naive-control animals. On day 20, a passive avoidance learning (PAL) test was used followed by sacrification and removal of the brain tissue in all animals. Brain TNF-α and ChAT levels were determined, and neurons in the hippocampal CA1 and CA3 regions were counted by Cresyl violet staining. RESULTS ICV-STZ was found to significantly shorten the latency time on the PAL, increase brain TNF-α level, and decrease brain ChAT activity and the number of neurons in the hippocampal CA1 and CA3 regions. On the other hand, rhEPO significantly attenuated all these detrimental effects induced by STZ. CONCLUSIONS RhEPO treatment significantly prevented the ICV-STZ-induced memory deficit by attenuating the hippocampal neuronal loss, neuroinflammation and cholinergic deficit in rats. This result suggests that rhEPO may be beneficial for treating AD.

Positive effects of ceftriaxone on pentylenetetrazol-induced convulsion model in rats

Aims: Many drugs have been associated with seizures as a side effect. Although they are defined as safe for nervous system. The effect on proconvulsant activity of beta lactam antibiotics have been also reported. We aimed to investigate whether ceftriaxone has an anticonvulsant effect on PTZ-induced seizures in rats. Materials and Methods: 36 male Sprague-Dawley rats, 18 of them for EEG recording and 18 of them are for behavioral studies, were randomly divided in two groups: group A for EEG recordings and group B for behavioral assesment. About 70 mg/kg PTZ was used for behavioral studies after Ceftriaxone administiration. About 35 mg/kg PTZ were used for EEG recording after ceftriaxone administiration. The electrodes were implanted on dura over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. The Racine convulsion scale, first myoclonic jerk onset time, spike percentages, brain MDA and SOD levels were evaluated between the groups. Results: First myoclonic jerk onset time was significantly shorter in saline group than both 200 and 400 mg/kg ceftriaxone groups (p < 0.05). Racines convulsion scale was significantly lower in 200 and 400 mg/kg ceftriaxone groups than saline group (p < 0.01, p < 0.0001). Both of two ceftriaxone groups have lower spike percentages than the saline group (p < 0.05). Significantly lower MDA levels and higher SOD activity were determined in 200 mg/kg ceftriaxone group compared with the saline group (p < 0.05). Conclusion: Our study demonstrated that ceftriaxone has protective effects on PTZ-induced convulsions and on oxidative damage associated with PTZ.

Regression of experimental endometriotic implants in a rat model with the angiotensin II receptor blocker losartan.

Endometriosis is a common disease in women of reproductive age, and many different treatments have been developed, although none has provided a cure. In this study, the efficacy of losartan, an angiotensin II type 1 receptor blocker and an antiangiogenic and anti‐inflammatory agent, on regression of experimental endometriotic implants in a rat model was investigated.

Comparison of skin effects of immediate treatment modalities in experimentally induced hydrofluoric acid skin burns.

Hydrofluoric acid (HF) burns cause immediate damage and painful long‐term sequellae. Traditionally, chelating agents have been used as the initial treatment for such burns. We have introduced epidermal growth factor (EGF) into an HF model to compare EGF with Ca2+ and Mg2+ treatments; 40 Sprague Dawley rats were divided into five groups. Each rat suffered a 6 × 4 cm2 burn induced by 40% HF. Group 1 had no treatment, group 2 had saline injected beneath the burn, group 3 received magnesium sulphate injections, group 4 received calcium gluconate and group 5 received EGF. Specimens were evaluated via planimetry and biopsy at intervals of 4, 8, 24 and 72 hours. Fluid losses were significantly less in the Mg2+ and EGF groups. The EGF group had the smallest burn area, least oedema, least polymorphonuclear granulocyte (PMN) infiltration, most angiogenesis and highest fibroblast proliferation of any group (P < 0·005). EGF limited HF damage morphologically and histologically more effectively than Ca2+ or Mg2+. This finding indicates that HF treatment via growth factors may be an improvement over chelation therapy.