Neslihan Yucel

Central nervous system protection by resveratrol in streptozotocin-induced diabetic rats

The objective of the present study was to investigate the possible neuroprotective effect of resveratrol against streptozotocin-induced hyperglycaemia in the rat brain and medulla spinalis. Thirty adult male Wistar rats were divided into three groups as follows: control group, streptozotocin-induced diabetic-untreated group, and streptozotocin-induced diabetic resveratrol-treated group. Diabetes was induced by a single injection of streptozotocin (STZ) (60 mg/kg body weight). Three days after streptozotocin injection, resveratrol (10 mg/kg) was injected intraperiteonally daily over 6 weeks to the rats in the treatment group. Six weeks later, seven rats from each group were killed and the brain stem and cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical studies (lipid peroxidation measuring malondialdehyde [MDA], xanthine oxidase [XO], nitric oxide [NO] and glutathione). MDA, XO and NO levels in hippocampus, cortex, cerebellum, brain stem and spinal cord in the streptozotocin-induced diabetic-untreated group increased significantly. Treatment with resveratrol significantly reduced MDA, XO and NO production and increased glutathione levels when compared to the streptozotocin-induced diabetic-untreated group. This study demonstrates that resveratrol is a potent neuroprotective agent against diabetic oxidative damage.

Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and histopathological recovery after experimental spinal cord injury

AbstractAim:To investigate the neuroprotective effect of resveratrol in an experimental spinal cord injury (SCI) model in rats.Methods:Male Wistar albino rats weighing 200–250 g were randomized into six groups. Weight-drop trauma was performed for SCI. Group 1 underwent laminectomy alone. Group 2 underwent laminectomy followed by SCI. Groups 3, 4, 5, and 6 underwent laminectomy followed by SCI and received resveratrol (100 mg/kg), methylprednisolone (MP) (30 mg/kg), resveratrol (100 mg/kg) plus MP (30 mg/kg), and ethanol (2%), respectively. The rats were divided into two subgroups for biochemical analysis (killed at 24 h after surgery) and for neurobehavioral and histopathological evaluation (killed at 6 weeks after surgery). Posttraumatic neurological recovery after surgery was recorded weekly.Results:Groups 3 and 5 revealed significantly lower malondialdehyde, nitric oxide, xanthine oxidase, and higher glutathione levels than group 4 (P<0.05). Neurological recovery rates were significantly better in groups 3 and 5 than group 4 (P<0.05). When spinal trauma size ratios were compared, there was no significant difference between treatment groups.Conclusion:Resveratrol treatment revealed better biochemical recovery in the acute stage of trauma than MP treatment. Although resveratrol and combined treatment revealed better neurobehavioral recovery than MP treatment; resveratrol, MP, and combined treatment modalities improved histopathological recovery at the same level in the final stage of the experiment. Future studies involving different doses of resveratrol and different doses combinations with MP could promise better results as each drug has a different anti-oxidative mechanism of action.

The histopathological evaluation of the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy in a rat model

Purpose: This study presents the histopathological evaluation of the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy. Materials and methods: Thirty-two Wistar rats were divided into four groups. The rats in Group 1 received melatonin and underwent radiation therapy. The rats in Group 2 received no melatonin and underwent radiation therapy. The rats in Group 3 received melatonin and underwent sham radiation therapy. The rats in Group 4 received no melatonin and underwent sham radiation therapy. Melatonin was administered at a dose of 100 mg/kg using an intraperitoneal injection. Radiation therapy was delivered on a Cobalt-60 unit using a single fraction of 18 Gy through an anterior portal covering the right lung in entirety. The rats underwent euthanasia at 6 weeks following radiation therapy. The lungs were dissected and blinded histopathological evaluation was performed. Results: Concerning the right lung, a decrease in intra-alveolar edema and intra-alveolar erythrocytes was observed despite an increase in activated macrophages, intra-alveolar fibrosis, hyaline arteriosclerosis and alveolar wall thickness for the rats in Group 1 as compared to the rats in Group 2. Concerning the left lung, a decrease in alveolar neutrophils and intra-alveolar erythrocytes was evident despite an increase in activated macrophages, hyaline arteriosclerosis and alveolar wall thickness for the rats in Group 1 as compared to the rats in Group 2. Conclusions: This study puts forward the histopathological evidence regarding the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy through restrained inflammation, regrettably at the expense of promoted fibrosis. The effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy needs to be evaluated further for the unresolved concerns regarding the safety.

Effect of pinealectomy and melatonin replacement on morphological and biochemical recovery after traumatic brain injury

Numerous studies showed that melatonin, a free radical scavenger, is neuroprotective. In this study, we investigated the effect of pinealectomy and administration of exogenous melatonin on oxidative stress and morphological changes after experimental brain injury.

Histopathological evaluation of melatonin as a protective agent in heart injury induced by radiation in a rat model.

INTRODUCTION Melatonin is a hormone which is known to be a powerful cardioprotective agent due to its free radical-scavenging properties. This study was carried out to evaluate whether melatonin administration prior to irradiation would have a protective effect on cardiac histopathological changes in an experimental rat model. METHODS Rats were divided into four groups. Single dose of 18 Gy radiation and sham radiation exposure were used in related groups. 50mg/kg dose of melatonin were injected intraperitonally 15 min prior to radiation exposure. Analyses and assessments were performed 6 months after radiation exposure. RESULTS Severe myocardial fibrosis was observed prominently in three regions: the apex, tips of papillary muscles and adjacent to the atrioventricular valves. Inflammation was found to be more in irradiated groups. Increased inflammation and fibrosis were in concordance. The number of mast cells was found to be decreased in irradiated groups. Myocyte necrosis and fibrosis were diminished with melatonin while vasculitis was prevented. CONCLUSIONS Elementary pathological lesions of radiation-induced heart disease (RIHD) are fibrosis, vascular damage, vasculitis and myocyte necrosis. Development of vasculitis was prevented by the use of melatonin. Fibrosis and necrosis were prominently decreased. Prevention of RIHD with the use of melatonin at the long term is encouraging according to the histopathological results.

Neuroprotective effect of etomidate on functional recovery in experimental spinal cord injury

Primary impact to the spinal cord causes rapid oxidative stress after injury. To protect neural tissue, it is important to prevent secondary pathophysiological mechanisms. Etomidate, a strong antiexcitotoxic agent, stimulates the gamma aminobutyric acid (GABA) receptors. The purpose of this study was to investigate neurobehavioral and histological recovery and to evaluate the biochemical responses to treatment of experimental spinal cord injury (SCI) in rats with etomidate or methylprednisolone (MP) or both etomidate and MP.

Obstetric admissions to the intensive care unit in a tertiary referral hospital

PURPOSE The present study was conducted to evaluate the obstetric admissions to the intensive care unit (ICU) in the setting of a tertiary referral hospital in an attempt to identify the risk factors influencing maternal outcome. MATERIALS AND METHODS All of the obstetric patients who seeked care for delivery at the emergency department and who were admitted to the ICU between January 2006 to July 2009 were retrospectively identified. The Simplified Acute Physiology Score (SAPS II) was calculated and the maternal mortality rate was estimated for each patient. The mean SAPS II scores and the mean estimated maternal mortality rates for the surviving patients and the nonsurviving patients were compared. RESULTS Seventy-three obstetric patients were admitted to the ICU. There were 9 maternal deaths and 24 fetal deaths. For the surviving group of patients, the mean SAPS II score was 34 and estimated maternal mortality rate was 20%, whereas for the nonsurviving group of patients, the SAPS II score was 64 and estimated maternal mortality rate was 73%. The difference between the surviving group of patients and the nonsurviving group of patients was statistically significant regarding both the mean SAPS II scores and the mean estimated maternal mortality rates. CONCLUSIONS Pregnancy-induced hypertensive disorders and hemorrhage appear as the major risk factors influencing maternal outcome in obstetric patients. Considering that the use of the SAPS II scores have enabled the reliable estimation of the mortality rates in the present study, the attempts at defining the focus of care for the obstetric patients who bear the major risk factors and who are admitted to the ICU should be carried out under the guidance of the ICU scoring systems such as the SAPS II.

Oxidative Stress in the in vivo DMBA Rat Model of Breast Cancer: Suppression by a Voltage-gated Sodium Channel Inhibitor (RS100642)

Breast cancer (BCa) was induced in vivo in female rats with 7,12‐dimethylbenz(a)anthracene (DMBA). Two main questions were addressed. Firstly, would the carcinogenesis be accompanied by oxidative stress as signalled by superoxide dismutase, glutathione peroxidase, malondialdehyde and total nitrate? Secondly, would treating the rats additionally with a blocker of voltage‐gated sodium channel (VGSC) activity, shown previously to promote BCa progression, affect the oxidative responses? The DMBA‐induced increases in the antioxidant systems were completely blocked by the VGSC inhibitor RS100642, which also significantly prolonged the lifespan. We conclude that VGSC inhibition in vivo can significantly protect against oxidative stress and improve survival from tumour burden.

Do sodium channel blockers have neuroprotective effect after onset of ischemic insult

Abstract Objective: Cerebral ischemia causes a series of pathophysiologic events that may result in cerebral infarct. Some neurons are more vulnerable to ischemia, particularly pyramidal neurons in the hippocampal CA1 region. Pharmacologic intervention for treatment of cerebral ischemia aims to counteract secondary neurotoxic events or to interrupt the progression of this process. In the present study, we compare the neuroprotective effects of sodium channel blockers (mexiletine, riluzole and phenytoin) and investigate whether they have neuroprotective effect when given after ischemic insult. Methods: A transient global cerebral ischemia model was performed in this study by clipping bilateral common carotid arteries during 45 minutes. Riluzole (8 mg/kg), mexiletine (80 mg/kg) and phenytoin (200 mg/kg) were injected into the rats intraperitoneally 30 minutes before or after reperfusion. Lipid peroxidation levels and cerebral water contents were evaluated 24 hours after ischemia. Histopathologic assessment of hippocampal region was determined 7 days after ischemia. Results: Riluzole, mexiletine and phenytoin treatment after global ischemia significantly decreased water content of the ischemic brain (p<0.05 for each). No significant difference was observed in cerebral edema among the drug treatment groups (p>0.05). When pre-treatment and post-treatment groups were compared with each other, only riluzole pre-treatment group revealed better result for cerebral edema (p<0.05). Pre-treatment with these drugs revealed significantly better results for the malonyldialdehyde (MDA) level and the number of survival neuron on the hippocampal region than the post-treatment groups. Conclusion: It is demonstrated that riluzole, mexiletine and phenytoin are potent neuroprotective agents in the rat model of transient global cerebral ischemia, but they are more effective when given before onset of the ischemia.

Neuroprotective effect of mexiletine in the central nervous system of diabetic rats

Both experimental and clinical studies suggests that oxidative stress plays an important role in the pathogenesis of diabetes mellitus type 1 and type 2. Hyperglycaemia leads to free radical generation and causes neural degeneration. In the present study we investigated the possible neuroprotective effect of mexiletine against streptozotocin-induced hyperglycaemia in the rat brain and spinal cord.30 adult male Wistar rats were divided into three groups: control, diabetic, and diabetic-mexiletine treated group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Mexiletine (50 mg/kg) was injected intraperitoneally every day for six weeks. After 6 weeks the brain, brain stem and cervical spinal cord of the rats were removed and the hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical analysis (the level of Malondialdehide [MDA], Nitric Oxide [NO], Reduced Glutathione [GSH], and Xanthine Oxidase [XO] activity). MDA, XO and NO levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group increased significantly, when compared with control and mexiletine groups (P < 0.05). GSH levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group decreased significantly when compared with control and mexiletine groups (P < 0.05).This study demonstrates that mexiletine protects the neuronal tissue against the diabetic oxidative damage.