Evaluation of the effects of sinapic acid and ellagic acid on sciatic nerve in experimental diabetic rats by immunohistochemical and stereological methods.

In our study, we aimed to examine the effects of sinapic acid and ellagic acid on neuropathy caused by diabetes in peripheral nerves. Fifty-six adult Wistar Albino rats Control, Diabetes, Diabetes+Sinapic Acid, Diabetes+Ellagic Acid, Diabetes+Sinapic Acid+Ellagic Acid, Sinapic Acid, Ellagic Acid and as Sinapic Acid+Ellagic Acid, they were randomly divided into eight groups(n:7). A single dose of 50 mg/kg streptozotocin(STZ) was administered intraperitoneally to the groups to be diagnosed with diabetes. Diabetes was accepted as blood glucose value of 250 mg/dL and above. Streptozotocin was given to the diabetes groups, 20 mg/kg/day intragastric Sinapic acid to the Sinapic acid groups, 50 mg/kg/day intragastric Ellagic acid to the Ellagic acid groups for 28 days. At the end of the experiment, 0.5 cm of the right sciatic nerve was removed. It was fixed in 10% formaldehyde. After histological follow-up, it was embedded in paraffin, 5 µm thick sections were taken. Immunohistochemical staining with Fibrinogen alpha, Laminin ß-1 and Collagen IV antibodies and stereological evaluation was performed by Physical Dissector Combination method. Collagen IV was used in control, diabetes and treatment groups showed similar immunostaining. Fibrinogen alpha was observed to be increased in the vessel wall in the diabetes group, while the uptake was minimal in the control and treatment groups. While Laminin ß-1 was increased in the diabetes group compared to the control group, immunostaining was observed in the treatment groups similar to the control group. It was observed that the total nerve area diabetes group decreased significantly compared to the control group, and the treatment groups, except for D+EA group were similar to the control group, but there was no statistically significant difference. The axon numbers in the diabetes group decreased significantly compared to the control group, and the treatment groups were similar to the control group, and there was no statistically significant difference (P > 0.05). It was determined that Sinapic Acid and Ellagic acid had positive effects on the nervous tissue in diabetic neuropathy.

Investigation of the pharmacological, behavioral, and biochemical effects of boron in parkinson-indicated rats.

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the central nervous system. In different studies, it has been investigated that boric acid has positive effects on different mechanisms that are important in PD. The aim of our study was to investigate the pharmacological, behavioral and biochemical effects of boric acid on rats with experimental PD with Rotenone. For this purpose, Wistar-albino rats were divided into 6 groups. Only normal saline was applied subcutaneously (s.c) to the first control and sunflower oil to the second control group. Rotenone was administered (s.c) to 4 groups (groups 3-6) at a dose of 2 mg/kg for 21 days. Only rotenone (2mg/kg, s.c) was administered to the third group. Boric acid was administered intraperitoneally (i.p.) at 5 mg/kg, 10 mg/kg, and 20 mg/kg to groups 4, 5, and 6, respectively. During the study, behavioral tests were applied to the rats, and then histopathological and biochemical analyzes were performed from the sacrificed tissues. According to the data obtained, a statistically significant difference (p<0.05) was observed between the Parkinson's group and the other groups in motor behavior tests, excluding the catalepsy test. Boric acid exhibited dose-dependent antioxidant activity. As a result of the histopathological and immunohistochemical (IHC) examination, a decrease in neuronal degeneration was observed at the increasing doses of boric acid, while gliosis and focal encephalomalacia were rarely encountered. There was a significant increase in tyrosine hydroxylase (TH) immunoreactivity, especially in group 6, with a dose of 20 mg/kg of boric acid. From these results, we conclude that the dose-dependent effect of boric acid may protect the dopaminergic system with antioxidant activity in the pathogenesis of PD. However, the effectiveness of boric acid on PD needs further investigation in a larger, more detailed study using different methods.

Effects of Cichorium intybus on serum oxidative stress, liver and kidney volume, and cyclin B1 and Bcl-2 levels in the brains of rats with ethanol induced damage.

We investigated the effects of an aqueous root extract of Cichorium intybus on Bcl-2 and cyclin B1 levels in the brain, kidney and liver volumes and changes of serum total antioxidant status (TAS) and total oxidant status (TOS) levels in ethanol induced damage in rats. The rats were divided into five groups: non-treated controls (C), maltodextrin in tap water treated (MD), 6.4% ethanol in tap water treated (ET), Cichorium intybus + maltodextrin in tap water treated (CI+MD), and Cichorium intybus + 6.4% ethanol in tap water treated (CI+ET). Rats in the CI+MD and CI+ET groups were treated with 200 mg/kg water extract of Cichorium intybus. Chronic ethanol aMDinistration significantly increased cyclin B1 and decreased Bcl-2 levels in the brain and significantly decreased TAS values, increased TOS values of serum and significantly decreased kidney volume in the ET group. There was no significant difference in the liver volume or liver cell count. Our data revealed that ethanol aMDinistration induces an overexpression of cyclin B1 and decreases levels of Bcl-2 in rat brains and induced oxidative stress in the blood. C. intybus treatment possessed a partial amelioration effect on cyclin B1 levels and TAS values.

Prenatal exposure to low-dose diclofenac sodium does not affect total neuron numbers in spinal segment T13 in rats.

The main purpose of the present study was to investigate the effects of diclofenac sodium (DS) on the total number of neurons in segment T13 of the spinal cord of offspring of pregnant rats using stereological methods. Eighteen adult female Wistar albino rats weighing 150-200g were used. Pregnant female rats were divided into three groups; a control group, a sham group and a DS (1mg/kg, intramuscular) exposed group. The DS and sham groups received injection from the 5th day of gestation to the 19th. Twenty eight days after birth, the offspring rats were perfused with 4% buffered formalin. T13, which is one of transverse spinal cord segments, were isolated and processed for routine paraffin histology. 5µm sections were obtained using a rotary microtome according to systematic random sampling strategies. Every 40th section was taken and sections were stained with modified Giemsa. All types of motor neuron cell were identified according to their morphology. In this study, the "disector-Cavalieri combination" method was used in the stereological examination of neurons. The motor neurons were counted in the right gray matter of the ventral horn in the spinal cord segment. The Kruskal-Wallis test was used for comparison the groups. In terms of motoneuron number, no significant difference among the groups was found (p>0.05). In conclusion, our results indicated that prenatal exposure to DS has no effect on the total number of motor neuron of the offspring rats.

Investigation of role of vascular endothelial growth factor, Annexin A5 and Apelin by immunohistochemistry method in placenta of preeclampsia patients.

Preeclampsia is a disease characterized by hypertension and proteinuria occurred after 20 weeks of gestation. Preeclampsia is a major cause of maternal and fetal morbidity and mortality.  The pathophysiological mechanism of preeclampsia is not known exactly yet. Preeclampsia endothelial cell dysfunction, associated with inadequate trophoblastic invasion is characterized by abnormal placentation. Vascular endothelial growth factor (VEGF) according to is an angiogenic cytokine, Annexin A5 is among endogenous peptides are both expressed from placental trophoblasts and Apelin is a multifunctional peptide and expressed by placental trophoblasts and endothelial cells. It was aimed to investigate roles of these parameters occurring in preeclampsia and to compare immunoreactivity of them in normal and preeclamptic placenta. In this study, placentas were collected from 20 normotensive pregnant women as controls, 16 mild-preeclamptic pregnant women, and 16 severe preeclamptic women. VEGF, Annexin A5 and Apelin were examined in samples of placenta tissues by streptavidin-biotin-peroxidase complex immunohistochemical methods. Immunoreactivity scores (IRS) were obtained for each parameter.  VEGF and Apelin IRS were increased significantly in preeclamptic groups compared with control group (p <0.026, p<0.002 respectively). But Annexin A5 IRS was decreased significantly in preeclamptic groups compared with control group (p<0.04). In correlation with the intensity of disease, increase in VEGF and Apelin, and decrease in Annexin A5 supports roles of hemo-dynamic alterations in fetoplacental circulation and structural alterations in uteroplacental bed occurring in preeclampsia.

Ribosome biogenesis mediates antitumor activity of flavopiridol in CD44+/CD24- breast cancer stem cells.

Flavopiridol is a synthetically produced flavonoid that potently inhibits the proliferation of human tumor cell lines. Flavopiridol exerts strong antitumor activity via several mechanisms, including the induction of cell cycle arrest and apoptosis, and the modulation of transcriptional regulation. The aim of the present study was to determine the effect of flavopiridol on a subpopulation of cluster of differentiation (CD)44+/CD24- human breast cancer MCF7 stem cells. The CD44+/CD24- cells were isolated from the MCF7 cell line by fluorescence-activated cell sorting and treated with 100, 300, 500, 750 and 1,000 nM flavopiridol for 24, 48 and 72 h. Cell viability and proliferation assays were performed to determine the inhibitory effect of flavopiridol. Gene expression profiling was analyzed using Illumina Human HT-12 v4 Expression BeadChip microarray. According to the results, the half maximal inhibitory concentration (IC50) value of flavopiridol was 500 nM in monolayer cells. Flavopiridol induced growth inhibition and cytotoxicity in breast cancer stem cells (BCSCs) at the IC50 dose. The present study revealed several differentially regulated genes between flavopiridol-treated and untreated cells. The result of the pathway analysis revealed that flavopiridol serves an important role in translation, the ribosome biogenesis pathway, oxidative phosphorylation, the electron transport chain pathway, carbon metabolism and cell cycle. A notable result from the present study is that ribosome-associated gene expression is significantly affected by flavopiridol treatment. The data of the present study indicate that flavopiridol exhibits antitumor activity against CD44+/CD24- MCF7 BCSCs through different mechanisms, mainly by inhibiting translation and the ribosome biogenesis pathway, and could be an effective chemotherapeutic molecule to target and kill BCSCs.

Resveratrol Treatment Prevents Hippocampal Neurodegeneration in a Rodent Model of Traumatic Brain Injury.

AIM: Traumatic brain injury (TBI) is a complex process. Increasing evidence has demonstrated that reactive oxygen species contribute to brain injury. Resveratrol (RVT) which exhibits significant antioxidant properties, is neuroprotective against excitotoxicity, ischemia, and hypoxia. The aim of this study was to evaluate the neuroprotective effects of RVT on the hippocampus of a rat model of TBI. MATERIAL AND METHODS: Twenty eight rats were divided into four groups. A moderate degree of head trauma was induced using Feeney"s falling weight technique. Group 1 (control) underwent no intervention or treatment. Head trauma was induced in Group 2 (trauma) and no drug was administered. Head trauma was induced in Group 3 and low-dose RVT (50 mg/kg per day) was injected. In Group 4, high-dose RVT (100 mg/kg per day) was used after head trauma. Brain tissues were extracted immediately after perfusion without damaging the tissues. Histopathological and biochemistry parameters were studied. RESULTS: Brain tissue malondialdehyde (MDA) levels in the trauma group were significantly higher than those in the control, lowdose RVT-treated, and high-dose-RVT-treated groups. The superoxide dismutase (SOD) levels in the control group were significantly higher than those in the trauma, low-dose RVT-treated, and high-dose RVT-treated groups. Glutathione peroxidase (GSH-Px) levels in the control group were significantly higher than those in the trauma and low-dose RVT-treated groups. The level of oxidative deoxyribonucleic acid (DNA) damage (8-OHdG/106 dG) in the trauma group was higher than that in the control group, low-dose RVT-treated, and high-dose RVT-treated groups. CONCLUSION: Resveratrol has a healing effect on neurons after TBI.

Neuroprotective Effects of Thymoquinone on the Hippocampus in a Rat Model of Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury is a leading cause of morbidity and mortality worldwide. We evaluated the neuroprotective effects of thymoquinone (TQ) in a rat model of traumatic brain injury by using biochemical and histopathologic methods for the first time. MATERIALS AND METHODS: Twenty-four rats were divided into sham (n = 8), trauma (n = 8), and TQ-treated (n = 8) groups. A moderate degree of head trauma was induced with the use of Feeney's falling weight technique, and TQ (5 mg/kg/day) was administered to the TQ-treated group for 7 days. All animals were killed after cardiac perfusion. Brain tissues were extracted immediately after perfusion without damaging the tissues. Biochemical procedures were performed with the serum, and a histopathologic evaluation was performed on the brain tissues. Biochemical experiments included malondialdehyde (MDA), reduced and oxidized coenzyme Q10 analysis, DNA isolation and hydroylazation, and glutathione peroxidase, and superoxide dismutase analyses. RESULTS: Neuron density in contralateral hippocampal regions (CA1, CA2-3, and CA4) 7 days after the trauma decreased significantly in the trauma and TQ-treated groups, compared with that in the control group. Neuron densities in contralateral hippocampal regions (CA1, CA2-3, and CA4) were greater in the TQ-treated group than in the trauma group. TQ did not increase superoxide dismutase or glutathione peroxidase antioxidant levels. However, TQ decreased the MDA levels. CONCLUSIONS: These results indicate that TQ has a healing effect on neural cells after head injury and this effect is mediated by decreasing MDA levels in the nuclei and mitochondrial membrane of neurons.