Protective effects of vortioxetine in predator scent stress model of post-traumatic stress disorder in rats: role on neuroplasticity and apoptosis.

Post-traumatic stress disorder (PTSD) can be observed after a traumatic event. The effect of an antidepressant vortioxetine (Vrx) against PTSD is unknown. The aim of this study was to investigate the possible protective effect of Vrx in the predator scent-induced PTSD rat model. The rats were exposed to dirty cat litter for 10 min and the protocol was repeated 1 week later with clean cat litter as a trauma reminder. The rats received Vrx (10 mg/kg/p.o.) or saline (1 ml/kg/p.o.) during 7 days between two exposure sessions. Novel object recognition test, hole board test, and elevated plus maze were performed. The b-cell lymphoma (bcl-2)/bcl-2-associated X protein (bax) ratio, brain-derived neurotrophic factor (BDNF), caspase-3 and -9 expressions were detected using Western blotting in the amygdaloid complex, hippocampus, and frontal cortex. Our results indicate that increased freezing time and anxiety index in the stress-induced group is decreased with Vrx application. Vrx treatment improved deteriorated recognition memory in the stress-induced group. Decreased bcl-2/bax ratio and BDNF level and increased caspase-3 and -9 expressions in the stress group, improved with Vrx in the amygdala, and hippocampus. Decreased bcl-2/bax ratio and increased casp-3 and -9 expressions in the stress group are ameliorated with Vrx in frontal cortex. The level of BDNF was increased with Vrx in the frontal cortex. Increased damage scores in the amygdaloid complex, hippocampal CA3, and frontal cortex in the stress group ameliorated with Vrx treatment. Our results show that if vortioxetine is administered immediately after trauma, it reduces anxiety, cognitive and neuronal impairment and may be protective against the development of PTSD.

Nesfatin-1 protects from acute pancreatitis: role of melanocortin receptors.

Nesfatin-1, a recently discovered peptide, was shown to have anti-inflammatory effects. Acute pancreatitis (AP) is a life-threatening condition caused by various reasons. Although the etiology of AP is well-known, its pathogenesis is not clear. The aim of this study is to investigate the possible anti-inflammatory role of nesfatin-1 and its probable protective underlying mechanisms in an acute pancreatitis model. Caerulein was applied intraperitoneally to induce acute pancreatitis in Sprague-Dawley female rats. Nesfatin-1 was administered 5 minutes before the application of caerulein to determine its potential anti-inflammatory role on AP. Five minutes before nesfatin-1 injection, in order to investigate the underlying mechanism, oxytocin receptor antagonist (atosiban), melanocortin receptor antagonist (HS024), or ghrelin receptor antagonist (cortistatin) were administered. Five minutes after nesfatin-1 administration, two doses of caerulein were applied one hour apart. The rats were sacrified 12 hours after the first caerulein dose for serum and pancreatic tissue sampling. Microscopic damage scoring, malondialdehyde and glutathione levels, myeloperoxidase activity, luminol and lucigenin chemiluminescence levels in pancreatic tissue and amylase, lipase, trypsinogen-2 levels in serum were evaluated. Oxidative damage was decreased with nesfatin-1 treatment in the acute pancreatitis model (P < 0.05 - 0.001). The administration of HS024 reversed the effect of nesfatin-1, via increasing lipase, amylase, trypsinogen-2, malondialdehyde (MDA), myeloperoxidase (MPO) and lucigenin levels (P < 0.05 - 0.01). Atosiban pre-treatment elevated MPO activity, luminol and lucigenin chemiluminescence levels (P < 0.01 - 0.001) and cortistatin increased lucigenin and luminol chemiluminescence (P < 0.05 - 0.01). Although receptor antagonists reversed the effect of nesfatin-1 on related biochemical parameters, no significant difference was found in histological scoring. Our results indicated that nesfatin-1 had an anti-inflammatory effect on acute pancreatitis via mainly effecting melanocortin receptors.

The effect of estrogen receptor agonists on pancreaticobiliary duct ligation induced experimental acute pancreatitis.

The 17ß-estradiol plays a role in physiology of pancreas and may protect it from inflammation. To examine the possible anti-inflammatory effects of 17ß-estadiol in pancreaticobiliary duct ligated (PBDL) acute pancreatitis (AP) model, and the underlying mechanism that 17ß-estradiol acts on, via evaluating the direct and the receptor related effects by using 17ß-estradiol, ER-α and -ß agonists. In the study both sexes of rats (n = 88) were used. Animals were divided into two groups as PBDL and PBDL + ovariectomized. ER-α agonist propyl-pyrazole-triol (PPT; 1 mg/kg/day), ER-ß agonist diarylpropionitrile (DPN; 1 mg/kg/day) and 17ß-estradiol (10 mg/kg/day) were administered to the groups for 3 days following AP induction. On the 3rd day, lung and pancreas tissues and serum samples were taken for malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), superoxide dismutase (SOD) and interleukin (IL) assays, and histological analyses. In both tissues of male and female AP groups MPO, MDA, SOD levels were increased (P < 0.05 - 0.01) and GSH levels were decreased (P < 0.05). Pancreas and lung MDA and SOD levels were improved with all treatments in female, except lung MDA levels of PPT-treated ones, while lung MDA and SOD levels were improved by PPT and 17ß-estradiol in females and via PPT in males (P < 0.05 - 0.001). The increased MPO levels were inhibited with PPT in male pancreas and female lung and with 17ß-estradiol in female pancreas (P < 0.05). The increased pro-inflammatory ILs were declined by treatments (P < 0.05 - 0.001). 17ß-estradiol and ER-α and -ß agonists reduced oxidative pancreatic and pulmonary damage. Estrogen and agonists might have protective role in AP.