Cytotoxic effects of Phenformin on ovarian cancer cells: expression of HIF-1α and PDK1 in the hypoxic microenvironment.

Today, many anticancer drugs are used clinically for ovarian cancer, one of the leading causes of cancer-related deaths in women. Phenformin is an antidiabetic drug of the biguanide class. It improves the antiproliferative activity in cancer cells. Hypoxia is an important component associated with ovarian cancer and its tumor microenvironment. The aim of this study was to investigate the anticancer effects of Phenformin in SKOV-3 human ovarian cancer cells under hypoxic conditions. SKOV-3 human ovarian cancer cells treated with different doses of Phenformin (0.5 mM, 1 mM, 2 mM, 5 mM) for 24 hours were subjected to WST-1 cell viability assay and Annexin V apoptosis assay. A dose-dependent decrease in cell viability with Phenformin treatment was observed. In addition, Phenformin activated percentage of apoptotic SKOV-3 cancer cells in a dose-dependent manner. In this study, Cobalt(II) chloride (CoCl2) treatment leads to increased hypoxia-inducible factor-1alpha (HIF-1α) expression and Phenformin can recover hypoxic condition. HIF-1α protein expression was significantly correlated with cell viability assay and apoptosis assay. We also found that Phenformin inhibits expression of phosphoinositide-dependent kinase 1 (PDK1) in SKOV-3 ovarian cancer cells. The ability to migrate to cancer cells was significantly reduced in a dose-dependent manner with Phenformin. This data demonstrates that Phenformin treatment can induce apoptosis and inhibit proliferation in ovarian cancer cells under hypoxic conditions. The findings reveal that HIF-1α is a new target for the treatment of ovarian cancer.

Demonstration of ameliorating effect of papaverine in sepsis-induced acute lung injury on rat model through radiology and histology.

BACKGROUND: Our target was to show the role of high mobility group box-1/receptor for (HMGB1/RAGE) interaction in feces intraperitoneal injection procedure (FIP)-induced acute lung injury (ALI) pathophysiology, to investigate the effect of papaverine on RAGE associated NF-κB pathway by determining the level of soluble RAGE (sRAGE) and HMGB1, and to support this hypothesis by evaluating inflammatory biochemical, oxidative stress markers, Hounsfield unit (HU) value in computed tomography (CT), and histo-pathological results. METHODS: FIP was performed on 37 Wistar rats for creating a sepsis-induced ALI model. The animals were assigned into four groups as follows: Normal control (no treatment), placebo (FIP and saline), and receiving 20 mg/kg and 40 mg/kg per day papaverine. Twenty h after FIP, CT examination was performed for all animals, and HU value of the lung parenchyma was measured. The plasma levels of tumor necrosis factor (TNF)-α, HMGB1, sRAGE, C-reactive protein (CRP) and malondialdehyde (MDA), and lactic acid (LA) were determined and PaO2 and PaCO2 were measured from arterial blood sample. Lung damage was assessed by histopathological. RESULTS: TNF-, IL-6, CRP, HMGB1, MDA, LA levels, histopathologic scores, and HU values of CT were significantly increased and sRAGE levels were decreased in the saline-treated group against normal group (all P<0.05). Papaverine significantly reversed all results regardless of the dose (all P<0.05) and demonstrated inhibition of HMGB1/RAGE interaction through increasing sRAGE levels and suppresses the pro-inflammatory cytokines. CONCLUSION: We concluded that papaverine has ameliorating effects in rat model of ALI.

Lacosamide exhibits neuroprotective effects in a rat model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that primarily affects the motor system. Although there are several treatments available to alleviate PD symptoms, there is currently no cure for the disease. Lacosamide, an anti-epileptic drug, has shown promising results in preclinical studies as a potential neuroprotective agent for PD. In this study, we aimed to investigate the neuroprotective effect of lacosamide in a murine model of PD. METHODS: Twenty-one adult male rats were randomly divided into the following three groups (n = 7): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1), and the others received stereotaxical infusion of rotenone (groups 2 and 3). The apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered lacosamide (20 mg/kg,i.p.) for 28 days. Apomorphine-induced rotation tests were performed to assess the effect of lacosamide on motor function. In addition, immunohistochemistry and biochemistry were used to assess the dopaminergic neuron loss in the substantia nigra and MDA, TNF-α and HVA levels, respectively. RESULTS: In rats with Parkinson's disease induced by rotenone, levels of malondialdehyde and TNF-α significantly increased and HVA levels decreased, whereas in mice treated with lacosamide, levels of malondialdehyde and TNF-α significantly decreased and HVA levels increased. The apomorphine-induced rotation test scores of lacosamide-treated mice were lower compared with the untreated group. Furthermore, treatment with lacosamide significantly mitigated the degeneration of dopaminergic projections within the striatum originating from the substantia nigra and increased tyrosine hydroxylase (TH) immunofluorescence, indicative of preserved dopaminergic neuronal function. CONCLUSION: In conclusion, our study provides evidence that lacosamide has a neuroprotective effect on the rat model of PD. Further studies are required to investigate the underlying mechanisms and evaluate the potential clinical use of lacosamide as a neuroprotective agent for PD.

Neuroprotection by melatonin against acrylamide-induced brain damage in pinealectomized rats.

The current study aimed to evaluate the neuroprotective effect of exogenous melatonin against acrylamide (ACR)-induced oxidative stress and inflammatory and apoptotic responses in the brain tissues in pinealectomized rats (PINX). ACR is a toxic chemical carcinogen that occurs owing to the preparation of carbohydrate-rich foods at high temperatures or other thermal processes. The rats who underwent pinealectomy and sham pinealectomy were exposed to ACR (25 mg/kg b.w., orally) alone or with exogenous melatonin (10 mg/kg b.w., i.p.) for 21 consecutive days. Alterations of brain oxidant/antioxidant status, dopamine (DA), Brain-Derived Neurotropic Factor (BDNF) inflammatory mediator and apoptosis during exposure to ACR in pinealectomized rats were more than without pinealectomized rats. Histopathological changes were more in brain tissue of pinealectomized rats after ACR administration. Exogenous melatonin treatment in ACR -exposed rats following pinealectomy increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) and improved brain total antioxidant status (TAS) compared to PINX+ACR. Moreover, melatonin suppressed lipid peroxidation, inflammatory pathways and apoptosis in ACR-intoxicated brain tissues. In addition, after exposure to ACR on pinealectomized rats, melatonin treatment ameliorated BDNF and DA levels in brain tissues. Furthermore, exogenous melatonin intervention in ACR-intoxicated rats significantly rescued the architecture of neuronal tissues. In summary, the present study, for the first time, suggested that exogenous melatonin treatment could reduce oxidative damage by increasing the activities of antioxidant enzymes, inhibiting lipid peroxidation and inflammation, and improving histopathological alterations in the brain tissue of pinealectomized rats after ACR administration.

Anticancer activity of linalool: comparative investigation of ultrastructural changes and apoptosis in breast cancer cells.

Breast cancer is the most common cancer in women in the world. Many anticancer drugs are currently used clinically have been isolated from plant species or are based on such substances. Linalool is aromatic compounds from the monoterpene group. It is the main constituents of essential oils and show antiproliferative, antioxidant, and antiseptic properties. The aim of this study was to investigate the antiproliferativeand apoptotic, effects of linalool in MCF-7 and MDA-MB-231 human breast cancer cells. MCF-7 and MDA-MB-231 human breast cancer cells were treated with different concentrations of linalool (100, 200, 400, 600, 800, 1000 µM) at 24 h and 48 h. MTT assay for cell proliferation and Annexin V assay for apoptosis was done. The morphology of breast cancer cells was investigated by light microscope and scanning electron microscope (SEM). The study show that linalool significantly induced apoptosis in all groups as dose and time-dependent (p < .05). Linalool has apoptotic and antiproliferative properties in a concentration and time-dependent manner in breast cancer cells. The cytotoxic effects of linalool on MCF-7 and MDA-MB-231 human breast cancer cells was found to be associated with apoptotic cell death. Linalool was more effective on MCF-7 human breast cancer cells in smaller amounts.

"Double hit" strategy: Removal of sialic acid from the dendritic cell surface and loading with CD44+/CD24-/low cell lysate inhibits tumor growth and metastasis by targeting breast cancer stem cells.

Cancer stem cells (CSCs), which represent the root cause of resistance to conventional treatments, recurrence, and metastasis, constitute the critical point of failure in cancer treatments. Targeting CSCs with dendritic cell (DC)-based vaccines have been an effective strategy, but sialic acids on the surface of DCs limit the interaction with loaded antigens. We hypothesized that removal of sialic acid moieties on immature DCs (iDCs) could significantly affect DC-CSC-antigen loading, thereby leading to DC maturation and improving immune recognition and activity. The lysate of CD44+/CD24-/low breast CSCs (BCSCs) was pulsed with sialidase-treated DCs to obtain mature dendritic cells (mDCs). The roles of cytoskeletal elements in antigen uptake and dendritic cell maturation were determined by immunofluorescence staining, flow cytometry, and cytokine measurement, respectively. To test the efficacy of the vaccine in vivo, CSCs tumor-bearing mice were immunized with iDC or mDC. Pulsing DCs with antigen increased the expression levels of actin, gelsolin, talin, WASp, and Arp2, especially in podosome-like regions. Compared with iDCs, mDCs expressed high levels of CD40, CD80, CD86 costimulatory molecules and increased IL-12 production. Vaccination with mDC: i) increased CD8+ and CD4 + T-cell numbers, ii) prevented tumor growth with anti-mitotic activity and apoptotic induction, iii) suppressed metastasis by decreasing Snail, Slug, and Twist expressions. This study reveals for the first time that sialic acid removal and loading with CSC antigens induces significant molecular, morphological, and functional changes in DCs and that this new DC identity may be considered for future combined immunotherapy strategies against breast tumors.

Digoxin Exhibits Neuroprotective Properties in a Rat Model of Dementia.

Alzheimer's disease (AD) is by far the most common cause of cognitive impairment in older adults. Current treatments are entirely focused on the symptoms of AD. A complex etiology for AD has been proposed recently, in which AD leads in elevated levels of inflammation. We previously studied digoxin's involvement in the sporadic-AD intracerebroventricular (ICV)-streptozotocin (STZ) animal model due to its anti-inflammatory and neuroprotective characteristics. 18 adult sprague-dawley rats were split into three groups: control (n = 6), STZ + Saline (n = 6), and STZ + Digoxin (n = 6). Twelve AD-induced rats were split into two groups using stereotaxy five days after STZ injection (3 mg/kg) into both lateral ventricles: one group got digoxin (0.1 mg/kg/day, i.p.) for three weeks, while the other group received saline. Following treatment, each subject was subjected to a passive avoidance learning (PAL) test, followed by brain tissue harvesting. The levels of tumor necrosis factor-alpha (TNF-α) and choline acetyl transferase (ChAT) were measured in the brain, and neurons were counted using Cresyl violet staining in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3) cornu ammonis (CA3). ICV-STZ significantly shortened PAL latency, increased brain TNF-α levels, decreased brain ChAT activity, and decreased hippocampus neuron number. On the other hand, digoxin significantly reduced all of these STZ-induced deleterious effects. Digoxin significantly rescued rats from memory loss caused by ICV-STZ by decreasing hippocampal cell death, neuroinflammation, and cholinergic deficiency. These findings suggest that digoxin may be beneficial in treating cognitive impairment and Alzheimer's disease.

Neuroprotective effects of dexpanthenol on streptozotocin-induced neuronal damage in rats.

AIM: Although the most common age-related neurodegenerative disease defined by memory loss is Alzheimer's disease (AD), only symptomatic therapies are present. A complex pathway for the AD pathogenesis that includes an increase in inflammation has recently been suggested. Since in previous animal experiments dexpanthenol has anti-inflammatory and neuroprotective activities, effects and role of dexpanthenol in an intracerebroventricular (ICV)-streptozotocin (STZ) induced sporadic-AD(memory impairment) animal model have been examined. DESIGN AND METHODS: In total, 18 adult sprague-dawley rats were classified into 3 groups; control (n = 6), STZ + Saline (n = 6) and STZ + Dexpanthenol (n = 6). Twelve AD-induced rats through STZ-injection (3 mg/kg) into both lateral ventricles via stereotaxy were separated into two groups five days after STZ administration: one of these groups was treated with dexpanthenol (1000 mg/kg/day, i.p.) for 3 weeks and the other with saline. A passive avoidance learning (PAL) test was used after treatment, followed by brain tissue extraction in all subjects. Brain levels of tumor necrosis factor-alpha (TNF-α) and choline acetyl transferase (ChAT) were measured and Cresyl violet staining was used to count neurons in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3). RESULTS: It was observed that ICV-STZ significantly shortened PAL latency, increased levels of TNF-α in brain, decreased activity of ChAT in brain, and number of hippocampal neurons. However, dexpanthenol significantly reduced all of those STZ-induced harmful effects. CONCLUSION: Dexpanthenol significantly prevented the memory deficit induced by ICV-STZ through mitigating neuronal loss in hippocampus, cholinergic deficiency and neuroinflammation in rats. These findings suggest that dexpanthenol may be beneficial for treating memory impairment.

Possibility of Taking an Offensive Stance in Extravasation Injury: Effects of Fat Injection in Vesicant (Doxorubicin) Induced Skin Necrosis Model in Rats.

INTRODUCTION: Extravasation injuries are one of the most feared complications of intravenous drug administration. The most common drugs associated with extravasation injury include chemotherapy agents and contrast media. Natural course of vesicant extravasation is discomfort, pain, swelling, inflammation, and ultimately skin ulceration. While diligence is the principle approach in prevention, immediate bed-side measures are as important in controlling the extent of tissue damage. Various options, either medical or interventional are next steps in treatment of the condition including antidotes, volume dilution, flushing, suction, hyperbaric oxygen therapy, and surgery. MATERIALS AND METHODS: 12 male Wistar albino rats were divided into two groups; one group received fat injections following subdermal doxorubicin infiltration in their right thighs, while other group received saline injection following subdermal doxorubicin infiltration in their right thighs for dilution. Left thighs of both groups were left untreated following subdermal doxorubicin infiltration. Total area of necrosis, as well as resultant epidermal thicknesses were assessed. Histological analyses were conducted using modified Verhofstad scoring system for comparison. RESULTS: Mean necrotic area was significantly smaller in the fat injection group compared to other groups. Median Verhofstad score was lesser in the fat injection group as well. Median epidermal thickness, on the other hand, was greater in the fat injection group. CONCLUSION: Injection of fat grafts following vesicant extravasation might be beneficial in preventing the progression of tissue damage, if employed early.

The neuro-restorative effect of adipose-derived mesenchymal stem cell transplantation on a mouse model of diabetic neuropathy.

Diabetic neuropathy (DN) is the most common degenerative complication associated with Diabetes Mellitus. Despite widespread awareness about DN, the only effective treatments are blood glucose control and pain management. The aim of the current study was to determine the effect of intramuscular adipose-derived mesenchymal stem cell (AMSC) transplantation on sciatic nerves in DN using EMG and histological analyses. A total of 27 mice were randomly divided into three groups: control group, DN group and AMSC group. In EMG, CMAP amplitude in the sciatic nerves was lower, but distal latency was higher in the DN group compared with the control group. CMAP amplitude in the sciatic nerves was higher in the AMSC group compared with the DN group. Distal latency in the sciatic nerve was lower in the AMSC group compared with the DN group. Histologic examination of the tissues in the animals treated with AMSC showed a remarkable improvement in microscopic morphology. Fluorescence microscopy analyses demonstrated that intramuscularly transplanted AMSC was selectively localized in the sciatic nerves. Transplantation of AMSC increased protein expression of S100, cdk2, NGF and DHH, all of which, interfered with DN onset in sciatic nerves. The findings of the present study suggest that AMSC transplantation improved DN through a signal-regulatory effect on Schwann cells, neurotrophic actions and restoration of myelination.

Short-term protective effect of octreotide on the lungs of rats with experimentally induced sepsis.

BACKGROUND: Acute respiratory distress syndrome is a devastating complication of severe sepsis. Preclinical models suggest that direct lung injury begins with attack to the lung epithelium, but indirect lung injury results from systemic endothelial damage due to inflammatory mediators. The aim of the present study was to explore the effect of octreotide on lungs in a surgically induced sepsis model in rats. METHODS: We used 32 male Sprague Dawley rats and divided into four groups. Group 1: Normal (non-operative and orally fed control, n=8); Group 2: Sham operated (n=8); Group 3: Cecal ligation and puncture (CLP) (untreated group, n=8); and Group 4: CLP and 100 µg/kg octreotide i.p. (n=8). For sepsis, CLP procedure was performed on 16 rats to induce a sepsis model. All groups were analyzed, their blood was taken for arterial blood gas analysis. For histological examination, lung tissues were removed and sections were prepared. RESULTS: In histological examination, if we compare CLP + Octreotide with only CLP group in CLP + Octreotide group decreased inflammatory cell infiltration in alveolar and interstitial area as well as edema, bleeding, when CLP group was compared with octreotide group, all histopathological parameters improved significantly and the severity index decreased from 3 to 1. For arterial blood gas, when CLP and octreotide groups were compared with CLP group, it was observed that there was a significant change in favor of healing and that they almost came up to controls and sham group. CONCLUSION: It could be hypothesized that it would be beneficial to administer octreotide for ameliorate lung injury state in sepsis patients.

Effects of pinealectomy and crocin treatment on rats with isoproterenol-induced myocardial infarction.

The present study aimed to analyze the effects of pinealectomy and crocin treatment in isoproterenol-induced myocardial damage. Seventy rats were divided into seven groups: control, sham control, pinealectomy (PNX), isoproterenol (ISO; 85 mg/kg on the 29th and 30th days of the experiment, subcutaneous injection), PNX + ISO, PNX + crocin (50 mg/kg/day for 30 days, intragastric administration), and PNX + ISO + crocin. PNX procedure was performed on the first day of the study. A significant increase was observed in serum cardiac damage markers (CK-MB, Troponin I) after ISO administration. ISO administration led to a significant increase in cardiac oxidative stress parameters, such as malondialdehyde (MDA) and total oxidant status (TOS), while it led to a decrease in antioxidant defense system parameters, such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) when compared to control groups. Elevated MDA and TOS levels were observed, while reduced SOD and CAT activities, and decreased GSH and TAS levels were observed in the group that underwent PNX and ISO administration when compared to the PNX group. Furthermore, in the PNX + ISO + Crocin group, SOD and CAT activities, and GSH and TAS levels ameliorated and MDA and TOS levels were reduced with the crocin treatment when compared to the PNX + ISO group. Also, marked increases were observed in serum cardiac markers, histopathological and immunohistochemical findings after the crocin treatment. All findings demonstrated that crocin could be employed as a cardioprotective agent due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.

The Restorative Effect of Gallic Acid on the Experimental Sciatic Nerve Damage Model.

OBJECTIVE: Peripheral nerve injuries occur mostly as a result of mechanical trauma. Due to the microvascular deterioration in peripheral nerve damage, it becomes challenging to remove free oxygen radicals. Gallic acid is a powerful antioxidant with anti-inflammatory effects and a free radical scavenger. The purpose of the study is to show that gallic acid contributes to the restorative effect in mechanical nerve damage, considering its antioxidant and anti-inflammatory effects. METHODS: Thirty male Sprague Dawley albino mature rats were included in the study. Ten of them constituted the control group, 10 out of 20 rats for which sciatic nerve damage was caused, constituted the saline group, and 10 formed the gallic acid group. Post-treatment motor functions, histological, immunohistochemical, and biochemical parameters of the rats were evaluated. RESULTS: Compared to the surgery+saline group, lower compound muscle action potential (CMAP) latency, higher CMAP amplitude, and higher inclined plane test values were found in the surgery+gallic acid group. Similarly, a higher nerve growth factor (NGF) percentage, a higher number of axons, and a lower percentage of fibrosis scores were observed in the surgery+gallic acid group. Finally, lower tissue malondialdehyde (MDA) and higher heat shock protein-70 (HSP-70) values were determined in the surgery+gallic acid group. CONCLUSION: Gallic acid positively affects peripheral nerve injury healing due to its anti-inflammatory and antioxidant effects. It has been thought that gallic acid can be used as a supportive treatment in peripheral nerve damage.

Antioxidant, anti-inflammatory, and anti-apoptotic effects of crocin against doxorubicin-induced myocardial toxicity in rats.

Doxorubicin (DOX) is a well-known chemotherapeutic drug for most malignancies including breast cancer and leukemia whilst the usage of DOX is limited owing to its cardiotoxicity. In the present study, we aimed to investigate the effects of crocin on doxorubicin-induced cardiotoxicity in rats. Forty rats were randomly divided into four groups: (a) control [received normal saline as a dose of 1 ml/kg by intraperitoneal injection (ip) for 15 days], (b) crocin (received crocin as a dose of 40 mg/kg/24h by ip for 15 days), (c) DOX (received DOX as a dose of 2 mg/kg/48h by ip in six injection, cumulative dose 12 mg/kg), and (d) DOX+crocin (received DOX as a dose of 2 mg/kg/48h by ip in six injection, and crocin as a dose of 40 mg/kg/24h i.p for 15 days). As compared to the controls, the results showed that DOX administration caused significant increases in lipid indices [triglyseride (TG), low-dencity lipoproteins (LDL) (p<0.001), and very low-dencity lipoproteins (VLDL) (p<0.005)], oxidative stress parameters [malondialdehyde (MDA) and total oxidant status (TOS) (p<0.001)] and cardiac markers [creatine kinase-muscle/brain (CK-MB) and cardiac troponin I (cTnI) (p<0.001)]. Besides, significant decreases in antioxidant defense systems [glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) (p<0.001)] were observed. The present study also demonstrated that co-administration of crocin with DOX significantly ameliorated the lipid profile (p<0.005), cardiac markers (p<0.005), and oxidative stress indices (p<0.001) as compared to DOX group. Histopathologically, significant increase in the mean histopathological damage score (MHDS) was found in the DOX group as compared to the controls (p<0.001). In contrast, the administration of crocin with DOX alleviated MHDS in myocardium (p<0.001). Taken together, our results reveal that crocin might be a cardioprotective agent in DOX-treated patients for cancer.

Dexpanthenol reduces fibrosis and aids repair following nerve laceration and neurorrhaphy.

The aim of the present study was to investigate the effect of dexpanthenol on nerve healing following neurorrhaphy in lacerated peripheral nerves. A total of 30 mature Sprague Dawley rats were used. Surgical sciatic nerve dissection and repair was performed on an experimental group of 20 rats. The remaining 10 rats were designated as the control group. The experimental group was divided into 2 subgroups. The surgery + saline group (SSLE; n=10) was given 1 ml/kg 0.9% sodium chloride saline intraperitoneally. The surgery + dexpanthenol group (SDPL; n=10) rats were given 500 mg/kg/day dexpanthenol intraperitoneally. Histological evaluation of the sciatic nerve tissue revealed that the fibrosis score was significantly lower in the SDPL group than in the SSLE group (P<0.001). Electrophysiological evaluation of compound muscle action potential (CMAP) indicated that the CMAP level in the SDPL group was significantly higher than that of the SSLE group (P<0.001), and the CMAP latency period was lower in the SDPL group compared with the SSLE group (P<0.001). In addition, the SDPL group malondialdehyde level was significantly lower than that of the SSLE group (P<0.001). Functional evaluation with an inclined plane test revealed a significant difference between the SSLE (39.6±5.5˚) and SDPL (79.1±6.93˚) groups (P<0.001). Dexpanthenol was observed to have a positive effect on nerve tissue repaired with neurorrhaphy in a rat sciatic model of laceration-type injuries similar to those frequently encountered in the clinic.

Comparison of the Effects of Extracorporeal Irradiation and Liquid Nitrogen on Nerve Recovery in a Rat Model.

AIM OF THE STUDY: Biologic reconstruction using tumor-bearing bone autografts devitalized by liquid nitrogen or extracorporeal irradiation (oncological sterilization) is a safe and effective method in musculoskeletal surgery. The purpose of this study was to examine the effects of these two oncological sterilization methods on nerve recovery. METHODS: A total of 48 rats were randomly divided into 3 groups as autograft, irradiation and liquid nitrogen groups. A nerve defect created in the right sciatic nerve was reconstructed with an autograft obtained from the nerve itself. Group I underwent reconstruction with standard nerve autograft. Group II and Group III underwent reconstruction with devitalized nerve autograft treated through extracorporeal irradiation and liquid nitrogen, respectively. The left sciatic nerves of the rats served as control. Electromyography, motor function test and histomorphological analysis were performed to assess the nerve recovery on the 3rd (early stage) and 4th months (late stage). RESULTS: Electrophysiological assessment revealed better results in irradiation group compared with liquid nitrogen group in terms of myelinization and axonal regeneration. Motor performance of the autograft group was slightly better than the other groups. Histologically, autograft group demonstrated better results compared with other groups. Late-stage assessments revealed high rates of myelinization in the graft segment in liquid nitrogen group and in the segment distal to the graft in irradiation group. CONCLUSIONS: This study has demonstrated that nerve autografts treated by oncological sterilization methods may be used for nerve reconstruction in limb salvage surgery. However, further studies are needed to clarify the applicability of these methods.

Oxytocin and cabergoline alleviate ovarian hyperstimulation syndrome (OHSS) by suppressing vascular endothelial growth factor (VEGF) in an experimental model.

PURPOSE: Ovarian hyperstimulation syndrome (OHSS) is a life-threatening complication of ovarian stimulation in reproductive medicine. Here, we aimed to investigate the role of oxytocin (OT) and cabergoline in the prevention and alleviation of the OHSS in an animal model. METHODS: Thirty-five female immature Wistar rats were randomly assigned to five groups. The control group (n = 7) received saline only for five consecutive days. Remaining twenty-eight rats received 10 IU of pregnant mare serum gonadotropin (PMSG) followed by 30 IU of human chorionic gonadotropin (hCG) to induce OHSS. Group 2 (n = 7) was managed with no additional intervention after the induction of OHSS. Group 3 (n = 7) received 100 µg/kg cabergoline 2 h before the PMSG injection for four consecutive days and 2 h before the hCG injection on the fifth day. Group 4 (n = 7) and group 5 (n = 7) received 80 µg/kg and 160 µg/kg OT after induction of OHSS, respectively. Oxytocin was administered 2 h before the PMSG injection for four consecutive days and 2 h before the hCG injection on the fifth day. Body and ovary weight, vascular permeability (VP), VEGF expression in the ovaries, and levels of VEGF in the peritoneal fluids were examined in all animals. RESULTS: Cabergoline and OT reduced body weight, ovary weight, and VP compared to that of the OHSS group (p < 0.05). VEGF expressions in ovaries and peritoneal VEGF levels were decreased in cabergoline and OT groups compared to that of the OHSS groups (p < 0.001 for cabergoline and OT-80 µg/kg; p < 0.00001 for OT-160 µg/kg). However, there was no statistically significant difference in these parameters between the OT and cabergoline groups. CONCLUSION: Both OT and cabergoline were active in the alleviation of OHSS through suppression of VEGF and VP. Overall, we conclude that OT is effective for downregulation for VEGF and improvement in vascular permeability in OHSS.

The Role of Ankaferd Blood Stopper and Oxytocin as Potential Therapeutic Agents in Endometriosis: A Rat Model.

To evaluate the potential effect of Ankaferd Blood Stopper (ABS) and oxytocin (OT) in an experimental endometriosis model, 18 female Sprague Dawley rats were used in this study. The animals were divided randomly into three groups after surgical induction of endometriosis: group 1: control group (isotonic NaCl, 1 mL/kg/day, intramuscular, n=6); group 2: OT group (OT, 80 U/kg/day, intramuscular, n=6); group 3: ABS group (ABS, 1.5 mL/kg/day, intraperitoneal, n=6). Each group was treated for four weeks (two times per week). Volumes of endometriotic explants were measured in biopsy samples for histopathological analysis. Vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor (TNF-α) levels were measured in plasma and peritoneal fluid. Endometriotic explant volumes were significantly decreased after OT administration (P<0.0001). The epithelial score was significantly decreased in both treatment groups compared to the control group (P<0.05). TUNEL immunohistochemistry showed more apoptotic changes in the endometriosis foci (gland epithelium and surrounding tissue) in the OT group than in the control group (P<0.05). The levels of VEGF, MCP-1, and TNF-α were significantly reduced in the OT group (P<0.05), whereas no significant changes in protein levels were found in the ABS-applied group. The results indicate that OT has greater potential as a therapeutic agent in experimentally induced peritoneal endometriosis, where ABS, which is a VEGF modulator, appears to act through different mechanisms to show its palliative effects on a rat model of peritoneal endometriosis.

Therapeutic effects of vitamin D on acetic acid-induced colitis in rats.

PURPOSE: To analyze the effect of calcitriol treatment on acute colitis in an experimental rat model. METHODS: A total of 24 adult Sprague Dawley albino rats were randomly separated into 3 equal groups: control group (n:8), colitis group (n:8), calcitriol administered group (n:8). A single dose of acetic acid (1 ml of 4% solution) was administered intrarectally to induce colitis. Group 1 was given 1 ml/kg 0.9% NaCl intraperitoneally; rats belonging to Group 2 were administered calcitriol 1 µg/kg for 5 days. RESULTS: Plasma tumor necrosis factor alpha, Pentraxin 3, and malondialdehyde levels were significantly lower in the calcitriol administered colitis group than in the standard colitis group (p<0.01). In the Calcitriol group, there was a significant histological improvement in hyperemia, hemorrhage and necrotic areas in the epithelium compared to the placebo group (p <0.000). CONCLUSION: The findings suggest that calcitriol may be an agent that could be used in acute colitis treatment.

Evaluation of the neuroprotective effects of ozone in an experimental spine injury model.

OBJECTIVE: The pathophysiology of spine injury consists of primary and secondary damage mechanisms. The vast majority of treatments aim to prevent or at least stop the progression of secondary neurotoxic events during the acute period. Ozone has been found to have potent antiinflammatory effects, to activate the immune system, and to have a substantial impact on the antioxidant system. In this study the authors aimed to evaluate the neuroprotective effects of ozone and their possible roles in recovery from spine injury, assessed based on biochemical, histological, and neurological parameters using an experimental spine injury model in rats. METHODS: The study included 31 female Wistar albino rats. The rats were divided randomly into 5 groups, with 7 rats in each group except the sham group, which contained 3 rats, as follows: group 1 (sham), laminectomy; group 2 (control), laminectomy and spinal trauma with no medical treatment (0.5 ml isotonic saline applied 1 hour postsurgery); group 3, single medical treatment with 30 mg/kg methylprednisolone applied intraperitoneally 1 hour after laminectomy and trauma; group 4, single medical treatment with 60 µg/ml ozone at 0.7 mg/kg applied intraperitoneally 1 hour after laminectomy and trauma; and group 5, double medical treatment with 30 mg/kg methylprednisolone and 60 µg/ml ozone at 0.7 mg/kg applied intraperitoneally 1 hour after laminectomy and trauma. After neurosurgery, neurobehavioral tests were performed in all groups. After 7 days of follow-up, all the rats were killed. Biopsy specimens obtained from trauma sites were examined using H & E, cresyl violet, immunohistochemical (anticonnexin-43), and TUNEL staining processes. Levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) and total oxidant status (TOS) and total antioxidant status (TAS) were measured in blood samples. RESULTS: The level of neurobehavioral healing was the highest in the double-treatment group (group 5), and the difference between the groups was significant. The minimum IL-6 level was found in group 5, indicating that the antiinflammatory impact was the most significant in this group (p = 0.01). Additionally, ozone was found to reduce oxidant stress more effectively than methylprednisolone (p = 0.03). Although methylprednisolone was superior to ozone in terms of the antiinflammatory effect, this effect was greater in group 5. Nevertheless, the number of neurons in group 5 was close to that of the control group, and the number of apoptotic cells was the least in group 5 (p < 0.001). CONCLUSIONS: In acute spinal injury, the combined application of methylprednisolone and ozone was found to have a greater antiinflammatory effect, hasten clinical recovery, and increase histological recovery compared with methylprednisolone therapy alone. This study showed that this combination therapy of methylprednisolone with the addition of ozone might have a more beneficial effect in the treatment of spinal injury than methylprednisolone therapy alone.