RESUMEN
Phoenixin-14 (PNX -14 ) is a newly identified neuropeptide with potential anti-inflammatory effects in the gastrointestinal tract. In this study, we evaluated the protective effect of PNX-14 against the formation of experimental indomethacin (IND)-induced duodenal ulcer. Thirty-two male Sprague-Dawley rats were randomly assigned to the four following study groups: (1) negative control (2) IND (7.5 mg/kg subcutaneous IND), (3) famotidine (FA) (7.5 mg/kg subcutaneous IND followed by 40 mg/kg intraperitoneal FA), and (4) PNX-14 (7.5 mg/kg subcutaneous IND followed by 50 µ/kg intraperitoneal PNX-14). Outcome measures included macroscopic evaluation of duodenal lesion, serum levels of IL-1ß, TNF-α, IL-6, and IL-12, and tissue biochemical parameters of oxidative stress, including malondialdehyde (MDA) , myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and catalase activity. Results The macroscopic grade of duodenal lesions were significantly smaller in the PNX-14 group than in the IND group (p < 0.001). Serum inflammatory cytokines were significantly increased in the IND group. PNX-14 treatment significantly decreased the serum levels of inflammatory cytokines (p < 0.0001). Oxidative contents (MDA and MPO activity) were significantly smaller in the PNX-14 group compared with the IND group (p < 0.0001), while anti-oxidative contents (SOD and catalase activity) were significantly more (p < 0.0001). PNX-14 was superior to FA in several anti-inflammatory properties, such as inhibiting the release of inflammatory cytokines and increasing the catalase activity. PNX-14 showed significant protective effects against the formation of IND-induced duodenal ulcers. These results suggest a promising therapeutic implication for PNX-14 in the treatment of gastrointestinal inflammatory disorders.
RESUMEN
The present study investigates the neuroprotective effects of modafinil-coated nanoparticle in rats' hippocampal CA1 region. Male Wistar rats (n = 48) were randomly divided into four groups. Then middle cerebral artery occlusion (MCAO) was performed by inserting a silicone coat filament in the right internal carotid artery via the external carotid artery until it reached the anterior cerebral artery. Modafinil (100 mg/kg) or modafinil-coated nanoparticle (100 mg/kg) was given to the rats as an oral gavage once a day. Infarct volume, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neuronal nuclear protein (NeuN) and Caspase-3 and, Caspase-8 as apoptotic genes were measured in the hippocampal CA1 region. Cresyl violet staining revealed that modafinil nanoparticle significantly decreased the neurodegeneration. Reverse transcription polymerase chain reaction results showed that modafinil nanoparticle use significantly increased the expression of neurotrophic factors (even more than modafinil alone group; p = .01). Moreover, the apoptotic markers were significantly decreased in nanoparticle modafinil (MN group); p < .05). The western blot analysis and Immunohistochemistry results confirmed the neuroprotective and anti-apoptotic effects of modafinil nanoparticle. This study's results showed that the use of modafinil-coated nanoparticle has neuroprotective effects by increasing neurotrophic factors and reducing apoptosis after MCAO in the CA1 area of the hippocampus. However, further studies are needed especially, in human samples.
Asunto(s)
Nanopartículas , Fármacos Neuroprotectores , Animales , Apoptosis , Factor Neurotrófico Derivado del Encéfalo , Factor Neurotrófico Derivado de la Línea Celular Glial , Hipocampo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Masculino , Modafinilo , Neuronas , Fármacos Neuroprotectores/farmacología , Proteínas Nucleares , Ratas , Ratas WistarRESUMEN
Systemic treatments for ischemic stroke as a disease with high disability and death have been yet unsuccessful. Combined treatments can potentially cause better results in treatment of patients with Stroke. In this study we assessed the neuroprotective effect of modafinil-coated gold nanoparticles (AuNPs) and mesenchymal stem cell (MSC) in ischemic stroke rats. Stem cells and AuNPs offer great promise for new medical treatments. 60 male Wistar rats were randomly divided into five groups (12 in each group): (1) the group that developed middle cerebral artery occlusion (MCAO or ischemia), (2) the normal group (control), (3) the MCAO group that received MSC (C + MCAO), (4) the MCAO group that received MSC and modafinil (CM + MCAO), and (5) the MCAO group that received MSC and modafinil-coated AuNPs (CMN + MCAO). Middle Cerebral Artery Occlusion (MCAO) was performed by inserting a silicone coat filament in the right internal carotid artery via the external carotid artery until it reached the anterior cerebral artery. The filament was located in the internal carotid artery for 60 min and then removed. Modafinil-coated AuNPs (100 mg/kg) or Modafinil (100 mg/kg) were given to the rats as an oral gavage, once a day in the morning time. Finally, infarct volume, BDNF (Brain-derived neurotrophic factor), GDNF (Glial cell-derived neurotrophic factor), NeuN (neuronal nuclear protein) expression, and cell apoptosis in brain were analyzed. The brain infarct volume and apoptosis significantly decreased and BDNF, NeuN, and GDNF increased in C + MCAO, CM + MCAO, and CMN + MCAO groups compared to ischemia. CMN + MCAO groups did not show significant difference in these factors compared to control group. These results demonstrated that the administration of stem cells and Modafinil-coated AuNPs at the same time had a good effect on ischemic brain injuries. It happened through increasing neurotrophic factors and decreasing brain cell apoptosis.