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.

The Effects of Lipid Emulsion, Magnesium Sulphate and Metoprolol in Amitriptyline-Induced Cardiovascular Toxicity in Rats.

The aim of this study was to evaluate the effects of metoprolol, lipid emulsion and MgSO4 which can be recommended for prevention of long QT that is one of the lethal consequences of amitriptyline intoxication. Thirty Sprague-Dawley male rats were included. Five groups respectively received the following: saline intraperitoneally (i.p.); amitriptyline (AMT) 100 mg/kg per os (p.o.) and saline i.p.; AMT 100 mg/kg p.o. and 5 mg/kg metoprolol i.p.; AMT 100 mg/kg p.o. and 20 ml/kg lipid emulsion i.p.; AMT 100 mg/kg p.o. and 75 mg/kg MgSO4 i.p. After 1 h, all groups were analysed by ECG recordings in DII lead; their blood was taken for biochemical examination and euthanasia was performed. For histological examination, cardiac tissues were removed and sections were prepared. QTc was significantly reduced in treatment groups compared to the AMT+saline group. When compared with the AMT+saline, lipid emulsion did not affect pro-BNP and troponin levels in biochemical analysis, but it significantly reduced Caspase 3 expression in histological examination. In the group treated with AMT and metoprolol, there was no significant effect on Caspase 3 expression. In MgSO4-treated group, there was a significant decrease in troponin, pro-BNP and urea levels biochemically and significant decrease in Caspase 3 expression histologically when compared with the control group. With further studies including clinical studies, MgSO4, lipid emulsion or metoprolol may be used to improve AMT-induced cardiotoxicity. They can possibly become alternative approaches in the future for suicidal or accidental intoxication of tricyclic antidepressant in emergency departments.

Oxytocin provides protection against diabetic polyneuropathy in rats.

PURPOSE: The aim of the present study is to investigate the protective effects of oxytocin (OT) on diabetic neuropathy (DNP) in rats. MATERIALS AND METHODS: Eighteen rats were used to induce diabetes using single dose streptozotocin (STZ, 60 mg/kg). Diabetic DNP was verified by electromyography (EMG) and motor function test on 21st day following STZ injection. Six rats served as naïve control group and received no drug (n = 6). Following EMG, diabetic rats were randomly divided into three groups and administered with either 1 ml/kg saline or 80 µg/kg OT or 160 µg/kg OT intraperitoneally for four weeks. Then, EMG, motor function test, biochemical analysis (plasma lipid peroxides and glutathione), histological, and immunohistochemical analysis of sciatic nerves (bax, caspase 3, caspase 9, and NGF) were performed. RESULTS: Diabetic rats developed neuropathy, which was apparent from decreased compound muscle action potentials amplitudes and prolonged distal latency in saline-treated rats (p < 0.001) whereas 160 µg/kg OT significantly improved EMG findings. OT treatment significantly lessened the thickening of perineural fibrosis when compared with saline group (p < 0.001). Besides, OT significantly reduced plasma lipid peroxides (p < 0.05) and increased glutathione levels in diabetic rats (p < 0.001). The sciatic nerves of saline-treated rats showed considerable increase in bax, caspase 3 and caspase 8 expressions (p < 0.001) while OT treatment significantly suppressed these apoptosis markers. Also, OT improved NGF expression in diabetic rats compared to saline group. CONCLUSION: Present results demonstrate that OT appears to alleviate harmful effects of hyperglycemia on peripheral neurons by suppressing inflammation, oxidative stress and apoptotic pathways.

Vinpocetine and Vasoactive Intestinal Peptide Attenuate Manganese-Induced Toxicity in NE-4C Cells.

Increased concentration of manganese (Mn) in the brain is known to be associated with excitotoxicity and neuroinflammation. Vinpocetine, an alkaloid derived from the plant Vinca minor L., basically shows its effect via phosphodiesterase inhibition and voltage-dependent Na+ channels. Vasoactive intestinal peptide (VIP) has gastrointestinal, vasomotor, muscular, and neuroprotective effects. The aim of this study was to examine the potential protective effects of vinpocetine and VIP against Mn toxicity in NE-4C neural stem cells (NSCs). VIP treatment at 1 µM and vinpocetine treatment at 2 µM concentrations were sufficient to yield maximum protection, and these concentrations were adopted in the following experiments. In this study, Mn treatment significantly increased lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) production, and triggered cell death in NE-4C cultures. However, significant reduction in LDH release was observed following vinpocetine or VIP treatments when compared with control. Similar to these findings, vinpocetine or VIP treatments significantly reduced membrane degradation induced by Mn (p < 0.001). Moreover, vinpocetine attenuated Mn-induced decrease of mitochondrial membrane potential. Similarly, proapoptotic protein bax and ROS production significantly decreased in cells after incubation with vinpocetine (p = 0.01) or VIP in the presence of Mn (p < 0.001). Our study provides the evidence that both vinpocetine and VIP may exert protective effects via modulating oxidative stress and apoptosis in Mn-induced neurodegeneration in NE-4C cells.

Oxytocin inhibits pentylentetrazol-induced seizures in the rat.

We aimed to reveal the anti-convulsant effects of oxytocin (OT) in pentylenetetrazol (PTZ)-induced seizures in rats. Thirty rats were randomly divided into 5 equal groups. Using stereotaxy, we implanted electroencephologram (EEG) electrodes in the left nucleus of the posterior thalamus. After 2 days, the first and second groups were used as the control and PTZ (35 mg/kg) groups, respectively. We administered 40, 80 and 160 nmol/kg OT+35 mg/kg PTZ to the rats, constituting the third, fourth, and fifth groups, respectively, for 5 days. At the end of 5 days, we recorded EEGs via bipolar EEG electrodes. After 12h, all groups except the first received 70 mg/kg PTZ and we determined the dose-response ratio. Racine's Convulsion Scale was used to evaluate seizures. The spike-wave complex percentage in the EEG was determined as 0% for the first group, 38.6%±7.2 for the second group, 36.4%±5.6 for the third group, 4.3%±1.8 for the fifth group and 4.1%±1.1 for the fifth group. The fourth and fifth groups had significantly decreased spike-wave complex percentages compared to the second group (p<0.0001). OT may prevent PTZ-induced epilepsy on an EEG. OT may also be considered for use in the treatment of epilepsy in the future.