Neşe Çölçimen

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 Feeneys 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.

Resveratrol treatment prevents hippocamal 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 Feeneys 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.

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.