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The basis of most neurological syndromes is the accumulation of free radical molecules. Quercetin is a polyphenolic bioflavonoid molecule and it has a very strong antioxidant effect by maintaining oxidative balance. There are many difficulties in the clinical use of quercetin due to its hydrophobic structure, low solubility, instability, poor oral bioavailability, and limited tissue-barrier penetration. Its synergistic use in complex with gold nanoparticles (AuNPs) could overcome these problems. AuNPs have recently emerged as an attractive candidate for delivery applications of various biomolecules and drugs. The aim of this study was to synthesize two different sized gold nanoparticles (AuNP20 and AuNP50) modified with polyethyleneimine (PEI) and quercetin, evaluate their potential neuroprotective effects on the in vitro oxidative stress model using DRG primary sensory neurons. It was shown that the antioxidant and anti-apoptotic ability of the bioflavonoid was preserved after exposure to the designed quercetin modified AuNPs. The PEI surface coating increased the stability and biocompatibility of the AuNPs in both sizes. It also potentially enables additional surface functionalization. This study indicates that designed nanoparticles (AuNP-Q-PEI) with different sizes could be a useful potential platform for the treatment of neurodegenerative syndromes or cancer diseases.
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OBJECTIVE: This study's objective was to identify the factors and impact of serums calcium 25-Hydroxy vitamin D, ferritin, uric acid, and sleeping disorders on benign paroxysmal positional vertigo (BPPV) patients. METHODS: This is a case and control design study. The consecutive patients' visits (age, older than 25 years) with idiopathic BPPV were recruited in the present study. For each patient, 3:1 sex and age-matched healthy people were assigned as the control. The study comprised 177 patients with BPPV and 656 controls. The study included biochemical, clinical, physical examinations, PSQI sleep quality, supine roll test, and Dix-Hallpike test for the diagnosis of all patients, and pure-tone audiometry (PTA) was used to assess hearing. Univariate and multivariate stepwise regression analyses were used for statistical analysis. RESULTS: The study comprised 833 patients with 295 males (35.4%) and 538 females (64.6%) who were between 25 and 70 years old. Of a total of 833 participants, 177 were BPPV patients, and 656 subject were normal. The results shown that there were significant differences between the BPPV and the normal group in terms of BMI (p = 0.039), physical activity (p = 0.003), cigarette smoking (p = 0.035), nargile-waterpipe use (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.001), congestive heart failure (CHF) (p < 0.001), neurology (p < 0.001), tinnitus (p < 0.001), dizziness (p < 0.001), headache (p < 0.001), vitamin D (p = 0.004), calcium (p = 0.004), magnesium (p < 0.001), potassium (p = 0.019), phosphorus (p < 0.001), haemoglobin (p < 0.001), serum glucose (p < 0.001), HbA1c (p < 0.001), triglyceride (p < 0.001), systolic BP (p = 0.004), diastolic BP (p = 0.008), and microalbuminuria (p = 0.005); ATP III metabolic syndrome (p = 0.038), IDF metabolic syndrome (p = 0.034), and poor sleep (p = 0.033). In terms of the type of BPPV, the posterior canal was the most commonly affected (n = 126, 71.2%), followed by the horizontal (n = 43, 24.3%) and anterior canal (n = 8, 4.5%). The analysis indicated that serum ferritin (p < 0.001), uric acid (p < 0.001), blood pressure (p < 0.001), dizziness (p < 0.001), cigarette-water-pipe smokers (p = 0.004), headaches/migraines (p = 0.005), calcium (p = 0.007), vitamin D deficiency (p = 0.008), sleepiness (p = 0.016), physical activity (p = 0.022), CHF (p = 0.024), and tinnitus (p = 0.025) were considered as risk predictors for BPPV. CONCLUSIONS: The results revealed that the serum levels of vitamin D, ferritin, uric acid, and calcium are low among the study population and supplementation could be considered as prevention in BPPV patients.
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Exposure of zebrafish embryos to glucose is a suitable model for the fetal hyperglycemia seen in gestational diabetes. Diethylhexyl phthalate (DEHP), which is considered an endocrine-disrupting chemical, is one of the most common phthalate derivatives used in stretching plastic and is encountered in every area where plastic is used in daily life. In the present study, the effects of DEHP on pathways related to insulin resistance and obesity were examined in zebrafish embryos exposed to glucose as a fetal hyperglycemia model. Zebrafish embryos were exposed to DEHP, glucose, and glucose + DEHP for 72 h post-fertilization (hpf), and developmental parameters and locomotor activities were monitored. At 72 hpf ins, lepa, pparγ, atf4a, and il-6 expressions were determined by RT-PCR. Glucose, lipid peroxidation (LPO), nitric oxide (NO) levels, glutathione S-transferase (GST), superoxide dismutase (SOD), and acetylcholine esterase (AChE) activities were measured spectrophotometrically. Compared with the control group, glucose, LPO, GST activity, il6, and atf4a expressions increased in all exposure groups, while body length, locomotor, and SOD activities decreased. While AChE activity decreased in the DEHP and glucose groups, it increased in the glucose + DEHP group. Although glucose exposure increased pparγ and lepa expressions, DEHP significantly decreased the expressions of pparγ and lepa both in the DEHP and glucose + DEHP groups. Our findings showed that DEHP amplified oxidant and inflammatory responses in this fetal hyperglycemia model, predisposing insulin resistance in zebrafish embryos.
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Dietilexilftalato , Hiperglicemia , Resistência à Insulina , Animais , Dietilexilftalato/toxicidade , Peixe-Zebra/metabolismo , Oxidantes , PPAR gama , Glucose/metabolismo , Hiperglicemia/induzido quimicamente , Superóxido DismutaseRESUMO
Parkinson's disease (PD) is the second most common neurodegenerative disease caused by the degeneration of dopaminergic neurons and the accumulation of Lewy bodies. Pain is one of the most common non-motor symptoms in PD, but the molecular mechanism of pain in PD is not fully understood, which prevents early diagnosis of PD. We aimed to determine the changes in opioidergic pathways when external pain is inflicted by inducing pain intraperitoneally in zebrafish, for which we generated a rotenone-induced PD model. After behavioural analyses in control(C), acetic acid (AA), rotenone (ROT), and rotenone+ acetic acid (ROT+AA) groups, catecholamine levels in brain tissue were determined by LC-MS/MS, expression of opioid peptides and their receptors by RT-PCR, expression of tyrosine hydroxylase by immunohistochemical method, and analyses of oxidant-antioxidant parameters by spectrophotometric methods. In the ROT group, distance travelled, average speed, and brain dopamine levels decreased, while LPO (lipid peroxidation) and NO (nitric oxide) increased as indicators of oxidative damage, and the SOD activity decreased. The mRNA expression of lrrk, pink1, and park7 genes associated with PD increased, while the mRNA expression of park2 decreased. This indicates that rotenone exposure is a suitable means to induce PD in zebrafish. The fact that body curvature was higher in the AA group than in the ROT and ROT+AA groups, as well as the decreased expression of penka, pdyn, and ion channels associated with the perception of peripheral pain in the ROT+AA group, suggest that mechanisms associated with pain are impaired in the rotenone-induced PD model in zebrafish.
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Doenças Neurodegenerativas , Fármacos Neuroprotetores , Doença de Parkinson , Animais , Peixe-Zebra , Rotenona/toxicidade , Ácido Acético/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Estresse Oxidativo , RNA Mensageiro , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologiaRESUMO
Background: Atherosclerosis, which is one of the leading causes of death all over the world, can create major or minor thromboembolic complications with the exponentially increasing diabetic status. Despite all the studies, the mechanism by which endothelial damage in atherosclerosis is triggered in diabetic setting is still not fully understood. Methods: In this study, tissue factor (TF), which is thought to act together in the formation of vasular endothelial growth factor (VEGF-A) and coagulopathy in diabetic atherosclerotic patients, may be an important indicator in this regard, a total of 100 cases who were undergone off-pump coronary artery bypass (OPCAB) which were at same risk group examined by dividing into diabetic status. Early postoperative process and biochemical parameters analyzed in terms of TF and VEGF-A levels measured before and after the operation. Results: TF and VEGF-A expression of the T1DM group were statistically high compared to non-diabetics. Significantly longer hospital stays with changes in TF and VEGF-A were found in patients in the diabetic group compared to pre- and postoperatively, respectively; TF (95% CI: 0.879-0.992; p = 0.025), VEGF-A (95% CI: 0.964-0.991; p = 0.001) and hospital stay (95% CI: 1.96-7.49; p = 0.0001). Preoperatively measured carotid intima-media thickness (CT) was higher in diabetics and was significantly associated with atrial fibrillation (AF), (r = 0.873). Surgical team and protocols were same and OPCAB procedures were routinely applied to all patients in our clinic. No minor or major events were observed in any of the cases. Conclusion: TF and VEGF-A values in patients with diabetic atherosclerosis may be important in the early detection of thromboembolic complications.
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Zebrafish (Danio rerio) is becoming an increasingly important model in epilepsy research. Pentylenetetrazole (PTZ) is a convulsant agent that induces epileptic seizure-like state in zebrafish and zebrafish embryos and is most commonly used in antiepileptic drug discovery research to evaluate seizure mechanisms. Classical antiepileptic drugs, such as valproic acid (VPA) reduce PTZ-induced epileptiform activities. Opioid system has been suggested to play a role in epileptogenesis. The aim of our study is to determine the effects of morphine in PTZ-induced epilepsy model in zebrafish embryos by evaluating locomotor activity and parameters related to oxidant-antioxidant status, inflammation, and cholinergic system as well as markers of neuronal activity c-fos, bdnf, and opioid receptors. Zebrafish embryos at 72 hpf were exposed to PTZ (20 mM), VPA (1 mM), and Morphine (MOR) (100 µM). MOR and VPA pretreated groups were treated with either MOR (MOR + PTZ) or VPA (VPA + PTZ) for 20 min before PTZ expoure. Locomotor activity was quantified as total distance moved (mm), average speed (mm/sec) and exploration rate (%) and analyzed using ToxTrac tracking programme. Oxidant-antioxidant system parameters, acetylcholinesterase activity, and sialic acid leves were evaluated using spectrophotometric methods. The expression of c-fos, bdnf, oprm1, and oprd1 were evaluated by RT-PCR. MOR pretreatment ameliorated PTZ-induced locomotor pattern as evidenced by improved average speed, exploration rate and distance traveled. We report the restoration of inflammatory and oxidant-antioxidant system parameters, c-fos, bdnf, and opioid receptor oprm1 as the possible mechanisms involved in the ameliorative effect of MOR against PTZ-induced epileptogenic process in zebrafish embryos.
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Epilepsia , Morfina , Pentilenotetrazol , Animais , Acetilcolinesterase , Anticonvulsivantes/uso terapêutico , Antioxidantes/metabolismo , Fator Neurotrófico Derivado do Encéfalo , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Inflamação , Morfina/uso terapêutico , Estresse Oxidativo , Pentilenotetrazol/toxicidade , Receptores Opioides/genética , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Ácido Valproico/uso terapêutico , Peixe-ZebraRESUMO
Disruption of the gut-brain axis in Parkinson's disease (PD) may lead to motor symptoms and PD pathogenesis. Recently, the neuroprotective potential of different PPARδ-agonists has been shown. We aimed to reveal the effects of erucic acid, peroxisome proliferator-activated receptors (PPARs)-ligand in rotenone-induced PD model in zebrafish, focusing on the gut-brain axis. Adult zebrafish were exposed to rotenone and erucic acid for 30 days. Liquid chromatography-mass spectrometry and tandem mass spectrometry (LC-MS/MS) analysis was performed. Raw files were analysed by Proteome Discoverer 2.4 software; peptide lists were searched against Danio rerio proteins. STRING database was used for protein annotations or interactions. Lipid peroxidation (LPO), nitric oxide (No), alkaline phosphatase, superoxide dismutase, glutathione S-transferase (GST), acetylcholinesterase and the expressions of PD-related genes were determined. Immunohistochemical tyrosine hydroxylase (TH) staining was performed. LC-MS/MS analyses allowed identification of over 2000 proteins in each sample. The 2502 and 2707 proteins overlapped for intestine and brain. The 196 and 243 significantly dysregulated proteins in the brain and intestines were found in rotenone groups. Erucic acid treatment corrected the changes in the expression of proteins associated with cytoskeletal organisation, transport and localisation and improved locomotor activity, expressions of TH, PD-related genes (lrrk2, park2, park7, pink1) and oxidant-damage in brain and intestines in the rotenone group as evidenced by decreased LPO, No and increased GST. Our results showed beneficial effects of erucic acid as a PPARδ-ligand in neurotoxin-induced PD model in zebrafish. We believe that our study will shed light on the mechanism of the effects of PPARδ agonists and ω9-fatty acids in the gut-brain axis of PD.
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Fármacos Neuroprotetores , PPAR delta , Doença de Parkinson , Animais , Doença de Parkinson/metabolismo , Rotenona , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Peixe-Zebra , Eixo Encéfalo-Intestino , Acetilcolinesterase , Cromatografia Líquida , Ácidos Erúcicos , Ligantes , Espectrometria de Massas em Tandem , Modelos Animais de Doenças , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Proteínas de Peixe-ZebraRESUMO
We aimed to evaluate how different types of toothpaste (TP) for children affected molecular mechanisms of odontogenesis in zebrafish embryos. Commercially available TPs were selected according to their detergent contents as the cocamidopropyl betaine (CAPB) containing TP (TP1) and sodium lauryl sulfate (SLS) containing TP (TP2). TP3 contained no detergent. Effects of SLS, and CAPB alone were also examined. TP and detergent concentrations affecting development were determined as 750 mg/L and 4 mg/L, respectively. Embryos were exposed to TP1, TP2, TP3, SLS, CAPB, and embryo medium (control) for 72 h post fertilization. Acetylcholinesterase (AChE) activity and oxidant-antioxidant parameters were analyzed spectrophotometrically. Expressions of tooth development genes were evaluated by reverse transcription PCR (RT-PCR). Intraocular distance, lower jaw, and ceratohyal cartilage length were displayed using Alcian Blue staining. axin2 and wnt10a expressions increased in SLS and TP2 groups. igf2a and eve1 expressions decreased in all groups except TP3. nrOb1 expression decreased in TP1, SLS, and CAPB groups. Oxidant-antioxidant balance was disturbed in all groups except TP3, evidenced by increased lipid peroxidation, nitric oxide. SLS, and CAPB groups were more affected in terms of AChE, glutathione-S-transferase, and superoxide dismutase; perturbations were observed in cartilage structures. Altered expression of tooth development gene axin2 correlated with wnt10a, and with changes in cartilage structures in SLS and TP2 groups. TP3 group presented no disruptions in oxidant-antioxidant balance. Our study shows the availability of externally developing zebrafish embryos in examining the effects of TP' contents on embryogenesis.
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Parkinson's disease (PD) is one of the most common forms of neurodegenerative diseases and research on potential therapeutic agents for PD continues. Rotenone is a neurotoxin that can pass the blood-brain barrier and is used to generate PD models in experimental animals. Boron is a microelement necessary for neural activity in the brain. Antioxidant, non-cytotoxic, anti-genotoxic, anti-carcinogenic effects of boric acid, the salt compound of boron has been reported before. Boronic acids have been approved for treatment by FDA and are included in drug discovery studies and pyridine boronic acids are a subclass of heterocyclic boronic acids used in drug design and discovery as substituted pyridines based on crystal engineering principles. The aim of our study was to determine the effect of 3-pyridinylboronic acid in rotenone-exposed zebrafish embryos, focusing on oxidant-antioxidant parameters and gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes gclm, gclc, hmox1a, nqo1, and PD related genes, brain-derived neurotrophic factor, dj1, and tnfα. Zebrafish embryos were exposed to Rotenone (10 µg/l); Low Dose 3-Pyridinylboronic acid (100 µM); High Dose 3-Pyridinylboronic acid (200 µM); Rotenone + Low Dose-3-Pyridinylboronic acid (10 µg/l + 100 µM); Rotenone + High Dose-3-Pyridinylboronic acid (10 µg/l + 200 µM) in well plates for 96 h post-fertilization (hpf). Our study showed for the first time that 3-pyridinylboronic acid, as a novel sub-class of the heterocyclic boronic acid compound, improved locomotor activities, ameliorated oxidant-antioxidant status by decreasing LPO and NO levels, and normalized the expressions of bdnf, dj1, tnf⺠and Nrf2 target genes hmox1a and nqo1 in rotenone exposed zebrafish embryos. On the other hand, it caused the deterioration of the oxidant-antioxidant balance in the control group through increased lipid peroxidation, nitric oxide levels, and decreased antioxidant enzymes. We believe that these results should be interpreted in the context of the dose-toxicity and benefit-harm relationship of the effects of 3-pyridinylboronic.
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Fármacos Neuroprotetores , Doença de Parkinson , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Boro/metabolismo , Boro/farmacologia , Ácidos Borônicos/metabolismo , Ácidos Borônicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Oxidantes , Estresse Oxidativo , Doença de Parkinson/metabolismo , Piridinas/farmacologia , Rotenona/toxicidade , Peixe-Zebra/metabolismoRESUMO
Obesity is an independent risk factor for type 2 diabetes and epigenetic regulatory mechanisms affect obesity-related mechanisms. Due to weight gain concern in society, artificial sweeteners with no nutritional value have been increasingly consumed. Stevia is a sweet natural glycoside and a calorie-free sweetner extracted from the leaves of Stevia rebaudiana Bertoni and used as a substitute for artificial sweetners. This study evaluates the effects of stevioside on glucose tolerance, epigenetic and metabolic regulators of insulin resistance, oxidant-antioxidant status and tissue histology in a diet-induced obese (DIO) zebrafish model. After 15 days of overfeeding body weight, and fasting blood glucose, lipid peroxidation and nitric oxide levels and the expressions of fbf21, lepa, ll21, tnfα were elevated, where as there was impaired glucose tolerance and lower superoxide dismutase and glutathione S-transferase activities, dnmt3a expression which is an epigenetic tool of insulin resistance. Beneficial effects of stevioside were observed on glucose tolerance, oxidative stress and inflammatory mediators linking obesity to insulin resistance and its epigenetic regulation, in DIO model.
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Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Hiperglicemia , Resistência à Insulina , Stevia , Animais , Glicemia/metabolismo , Dieta , Diterpenos do Tipo Caurano , Epigênese Genética , Glucose , Glucosídeos , Humanos , Obesidade , Estresse Oxidativo , Stevia/metabolismo , Peixe-Zebra/metabolismoRESUMO
Parkinson's disease (PD) is one of the most common neurodegenerative diseases due to the loss of dopaminergic neurons in the midbrain in the substantia nigra. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxic agent causing disruptions in mitochondria of dopaminergic neurons leading to impaired oxidant-antioxidant balance. Both zebrafish and zebrafish embryos are sensitive to MPTP. In zebrafish embryos, MPTP decreases the dopaminergic cells in the diencephalon by damaging dopaminergic neurons. Morphine is an opioid pain killer and a strong analgesic that is used to treat chronic pain. Until today morphine has been shown to regulate the survival or death of neurons and both protective and destructive effects of morphine have been reported in the central nervous system. This study aimed to evaluate the effects of morphine in MPTP-exposed zebrafish embryos. Developmental parameters were monitored and documented daily during embryonic development. Locomotor activity of zebrafish embryos at 96 h postfertilization (hpf) was determined. Acetylcholinesterase (AChE) activity and oxidant-antioxidant parameters were analyzed by biochemical methods. RT-PCR was used to evaluate bdnf, dj1, lrrk and pink1 expressions. Morphine treatment improved mortality and hatching rates, locomotor activity, AChE, and antioxidant enzyme activities as well as the expressions of bdnf, dj1, lrrk and pink1 in a dose-dependent manner that were altered by MPTP. Increased lipid peroxidation supports the role of morphine to induce autophagy to prevent PD-related pathologies. Our study provided important data on the possible molecular mechanism of the therapeutic effects of morphine in PD.
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Intoxicação por MPTP , Fármacos Neuroprotetores , Síndromes Neurotóxicas , Animais , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/uso terapêutico , Acetilcolinesterase/metabolismo , Analgésicos Opioides/metabolismo , Analgésicos Opioides/uso terapêutico , Antioxidantes/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Morfina/farmacologia , Intoxicação por MPTP/tratamento farmacológico , Intoxicação por MPTP/prevenção & controle , Intoxicação por MPTP/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxidantes/metabolismo , Proteínas Quinases/metabolismo , Peixe-ZebraRESUMO
Among the mechanisms underlying Parkinson's disease, many pathogenic mechanisms are suggested to be effective such as oxidative stress, mitochondrial dysfunction, disruption of the ubiquitin-proteasome system, and neuroinflammation. Calcium is very important for neuronal and glial cells, neurodegenerative disease mechanisms are closely related to disturbed calcium homeostasis. Recent studies strongly support the role of inflammation in nigrostriatal degeneration in PD. In recent years, Rifampicin, a macrocyclic antibiotic has been shown to have a protective effect on neurons. This study aims to evaluate the effects of rifampicin in the experimental PD model induced by rotenone in zebrafish focusing on the relationship between calcium-dependent mitochondrial dysfunction and inflammation. Adult zebrafish were exposed to rotenone and rifampicin for 3 weeks. Locomotor activity was determined as the total distance that the zebrafish traveled for 5 min. Neuroinflammation and PD-related gene expressions were determined by RT-PCR. Mitochondrial calcium levels were determined using inductively coupled plasma-optical emission spectrometry (ICP-OES). Gamma synuclein, Park 7, Sigma-1 receptor expressions were determined by Western Blot. Our results show that rifampicin may be effective in reducing neuroinflammation, which may be an effective strategy to reduce mitochondrial dysfunction due to impaired calcium homeostasis in PD.
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Doenças Neurodegenerativas , Rotenona , Animais , Cálcio/metabolismo , Homeostase , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Mitocôndrias , Doenças Neurodegenerativas/metabolismo , Doenças Neuroinflamatórias , Estresse Oxidativo , Rifampina/toxicidade , Rotenona/toxicidade , Peixe-Zebra/metabolismoRESUMO
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that damages dopaminergic neurons. Zebrafish has been shown to be a suitable model organism to investigate the molecular pathways in the pathogenesis of Parkinson's disease and also for potential therapeutic agent research. Boron has been shown to play an important role in the neural activity of the brain. Boronic acids are used in combinatorial approaches in drug design and discovery. The effect of 3-pyridinylboronic acid which is an important sub-class of heterocyclic boronic acids has not been evaluated in case of MPTP exposure in zebrafish embryos. Accordingly, this study was designed to investigate the effects of 3-pyridinylboronic acid on MPTP exposed zebrafish embryos focusing on the molecular pathways related to neurodegeneration and apoptosis by RT-PCR. Zebrafish embryos were exposed to MPTP (800 µM); MPTP + Low Dose 3-Pyridinylboronic acid (50 µM) (MPTP + LB) and MPTP + High Dose 3-Pyridinylboronic acid (100 µM) (MPTP + HB) in well plates for 72 hours post fertilization. Results of our study showed that MPTP induced a P53 dependent and Bax mediated apoptosis in zebrafish embryos and 3-pyridinylboronic acid restored the locomotor activity and gene expressions related to mitochondrial dysfunction and oxidative stress due to the deleterious effects of MPTP, in a dose-dependent manner.
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Intoxicação por MPTP , Peixe-Zebra , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Ácidos Borônicos/metabolismo , Ácidos Borônicos/uso terapêutico , Modelos Animais de Doenças , Intoxicação por MPTP/tratamento farmacológico , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/patologia , Camundongos , Camundongos Endogâmicos C57BL , Piridinas , Pirrolidinas/metabolismo , Pirrolidinas/uso terapêutico , Peixe-Zebra/metabolismoRESUMO
Ketosis is a potentially beneficial metabolic state for health especially in neurological conditions including Parkinson's disease (PD). Medium-chain-triglycerides (MCT) have specific metabolic properties and they are described as ketogenic even without restriction of carbohydrate. Octanoic acid (C8) is the main MCT showing this effect. Rotenone is a neurotoxin that is used to induce experimental PD model. Rotenone inhibits mitochondrial respiratory complex 1 (MRC1) and causes reactive oxygen species formation. Mass spectrometry (MS)-based phosphoproteomic methods enable discovering specific signaling events in special molecular pathways through identification and quantification of phosphoproteins. Signaling networks involved in rotenone-mediated biological processes and beneficial effects of MCTs on neurodegenerative diseases are not well understood. We aimed to gain comprehensive molecular perspective on the global phosphoproteome differences in rotenone-exposed zebrafish treated with octanoic acid. Raw files obtained from MS analysis were processed and searched against the Danio rerio protein database using SEQUEST-HT algorithm to identify and quantify phosphopeptides with 2,569 unique phosphoproteins and 4,161 unique phosphopeptides corresponding to 2005 proteins. Microtubule-associated protein (MAP) family members were significantly lower in rotenone group. Phosphoproteins involved in ion binding (calcium, magnesium, zinc ion), oxygen binding, microtubule binding, ATP- and GTP-binding were among differentially expressed 347 proteins in rotenone group and they were reversed after octanoic acid treatments. Phosphoproteins and phosphorylation sites were identified for future exploration of signaling pathways involved in rotenone toxicity. We believe our findings might help in the formulation of effective therapeutic strategies for the treatment of PD using ketogenic formulations involving MCTs. PRACTICAL APPLICATIONS: Ketosis is a potentially beneficial metabolic state for health especially in neurological conditions including Parkinson's disease (PD). Medium-chain-triglycerides (MCT) (C6-C12) have specific metabolic properties making them described as ketogenic even without restriction of carbohydrate. Octanoic acid (caprylic acid, C8) is the main MCT showing this effect. Our findings might help in the formulation of effective therapeutic strategies for the treatment of Parkinson's disease using ketogenic formulations involving Medium-chain-triglycerides.
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Doença de Parkinson , Rotenona , Animais , Caprilatos/toxicidade , Rotenona/toxicidade , Peixe-ZebraRESUMO
BACKGROUND: Dysfunction of the gastrointestinal tract (GIT) is one of the most common non-motor symptom of Parkinson's Disease (PD). Pathological processes causing PD were suggested to initiate in the enteric nervous system (ENS) and proceed to the central nervous system (CNS). There are studies showing that low-carbohydrate ketogenic diets can improve motor symptoms of PD. Caprylic acid (C8) is the principal fatty acid component of the medium-chain triglycerides in the ketogenic diets. In this study, we aimed to evaluate the effects of caprylic acid, in neurotoxin exposed zebrafish focusing on the relationship between intestinal and brain oxidative stress and inflammation. METHODS: Adult zebrafish were exposed to rotenone (5 µg/L) (R group) and caprylic acid (20 and 60 mg/mL) (L + HDCA and R + HDCA groups) for 30 days. At the end of 30 days locomotor activities were determined. Levels of lipid peroxidation (LPO), nitric oxide, glutathione and superoxide dismutase and glutathione S-transferase activities were determined by spectrophotometric methods and gene expressions of tnfâº, il1, il6, il21, ifnÉ£ and bdnf were evaluated by RT-PCR in the brain and intestinal tissues of zebrafish. RESULTS: Caprylic acid ameliorated LPO, NO, SOD and the expressions of tnfâº, il1, il6, il21, ifnÉ£ and bdnf in brain and intestines. Locomotor activities were only ameliorated in high dose R + HDCA group. CONCLUSIONS: Caprylic acid ameliorated the neurotoxin-induced oxidative stress and inflammation both in the brain and intestines and enhanced locomotor activity in zebrafish.
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Eixo Encéfalo-Intestino/fisiologia , Caprilatos/farmacologia , Animais , Encéfalo/metabolismo , Eixo Encéfalo-Intestino/efeitos dos fármacos , Caprilatos/metabolismo , Modelos Animais de Doenças , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Glutationa/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo , Rotenona/efeitos adversos , Superóxido Dismutase/metabolismo , Peixe-Zebra , Proteínas de Peixe-ZebraRESUMO
Thermal trauma can damage organs away from the skin burn site and lead to multiple organ dysfunction. Following thermal injury, all tissues are exposed to ischemia, and as a result, resuscitation and reperfusion occur during the burning shock. Burn damage starts systemic inflammatory reactions that produce toxins and reactive oxygen radicals that lead to peroxidation. This study aimed to investigate, for the first time, the possible antioxidant effects of Myrtus communis ethanol extract on burn-induced oxidative distant organ injury orally. The thermal trauma was generated under ether anesthesia by exposing the dorsum of rats to 90 °C water bath for 10 s. 100 mg/kg/day Mrytus communis ethanol extract was applied orally for two days. Malondialdehyde (MDA) and glutathione (GSH) levels, glutatinone-S-transferase (GST), superoxidedismutase (SOD) and catalase (CAT) activities were determined to detect the possible antioxidant effects of myrtle on small intestine and lung tissues. Burn damage significantly increased MDA levels in lung and small intestine tissues, and significantly decreased GSH levels, CAT and GST activities in the small intestine and lung tissues compared to control group. Mrytus communis ethanol extract decreased MDA level and increased GSH level, SOD, CAT and GST activities significantly in either small intestine or lung tissues. Mrytus communis extract may be an ideal candidate to be used as an antioxidant adjunct to improve oxidative distant organ damage to limit the systemic inflammatory response and decreasing the recovery time after thermal injury.
Assuntos
Antioxidantes/uso terapêutico , Queimaduras/tratamento farmacológico , Intestino Delgado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Myrtus/química , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Glutationa/metabolismo , Intestino Delgado/metabolismo , Pulmão/metabolismo , Malondialdeído/metabolismo , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , CicatrizaçãoRESUMO
The amount of technological products including television, radio transmitters, and mobile phone that have entered our daily life has increased in recent years. But these devices may cause adverse effects on human health. Electromagnetic shielding fabrics may limit and inhibit electromagnetic waves. Aim of our study was to evaluate electromagnetic wave blocking performance of nonwoven textile surfaces on zebrafish embryos that were exposed to electromagnetic waves at specific frequencies. Oxidant-antioxidant system parameters were evaluated spectrophotometrically. The expressions of tp53 and casp3a were evaluated by RT-PCR. Results showed that electromagnetic shielding fabrics produced as conductive nonwoven textile surfaces improved oxidant-antioxidant status and tp53 expression that were impaired in electromagnetic waves exposed zebrafish embryos. Also, electromagnetic shielding fabrics decreased casp3a expression responsible for the execution phase of apoptosis that increased in electromagnetic waves exposed zebrafish embryos.
Assuntos
Apoptose , Radiação Eletromagnética , Embrião não Mamífero/patologia , Estresse Oxidativo , Substâncias Protetoras/farmacologia , Têxteis , Peixe-Zebra/embriologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/enzimologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Peixe-Zebra/genéticaRESUMO
Endocrine disrupting chemicals (EDCs) are defined as exogenous substances that can alter the development and functioning of the endocrine system. The Wnt signaling pathway is an evolutionarily conserved pathway consisting of proteins that transmit cell-to-cell receptors through cell surface receptors, regulating important aspects of cell migration, polarity, neural formation, and organogenesis, which determines the fate of the cell during embryonic development. Although the effects of EDCs have been studied in terms of many molecular mechanisms; because of its critical role in embryogenesis, the Wnt pathway is of special interest in EDC exposure. This review provides information about the effects of EDC exposure on the Wnt/ß-catenin pathway focusing on studies on bisphenol A, di-(2-ethylhexyl) phthalate, diethylstilbestrol, cadmium, and 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Assuntos
Disruptores Endócrinos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/fisiologia , Compostos Benzidrílicos/farmacologia , Cádmio/farmacologia , Dietilexilftalato/farmacologia , Dietilestilbestrol/farmacologia , Humanos , Fenóis/farmacologia , Dibenzodioxinas Policloradas/farmacologiaRESUMO
Thermal skin burns cause local injury as well as triggers acute systemic inflammation response where the imbalance between oxidative and antioxidative system occurs. As an alternative treatment, various medicinal herbs are used to treat burn injuries in many countries. In this study, the possible protective role of oral or topical Myrtle (Myrtus communis L.) treatment against burn-induced damage was investigated. The dorsum of the Wistar Albino rats was shaved and exposed to 90 °C water bath in burn group or 25 °C water bath in control group for 10 s under ether anesthesia. Myrtle extract was applied 100 mg/kg/day for 2 days either orally or topically. In skin samples; malondialdehyde and glutathione levels, catalase, superoxide dismutase, nitric oxide and tissue factor activities were determined. Skin tissues were also examined by light microscopy. Severe thermal skin burn injury caused a significant decrease in glutathione level, superoxide dismutase, catalase and tissue factor activities as well as nitric oxide level, which was accompanied with significant increases in skin malondialdehyde level. Myrtle treatment reversed all these biochemical indices except topical Myrtle treated group's nitric oxide level, as well as histopathological alterations, which were induced by thermal trauma. Both oral and topical Myrtle extract treatment was found to have protective role in the burn induced oxidative injury, which may be attributed to the potential antioxidant effect of Myrtle. As a conclusion, Myrtle significantly diminishes burn-induced damage in skin.
Assuntos
Antioxidantes/farmacologia , Queimaduras/metabolismo , Myrtus , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Administração Cutânea , Administração Oral , Animais , Queimaduras/patologia , Catalase/efeitos dos fármacos , Catalase/metabolismo , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Pele/lesões , Pele/metabolismo , Pele/patologia , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Tromboplastina/efeitos dos fármacos , Tromboplastina/metabolismoRESUMO
Circadian rhythm in all living organisms is disturbed continuously by artificial light sources and artificial lighting has become a hazard for public health. Circadian rhythm of melatonin maintains high levels of melatonin during the night and low levels during the day. N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) is one of the four enzymes required for melatonin synthesis and mtnr1ba is a melatonin receptor-encoding mRNA that is expressed widely in the embryonic brain. Pax7 has important roles during neural crest development and especially xanthophore pigmentation. Due to its diurnal nature, zebrafish provide a special opportunity for research on circadian rhythms that are regulated by melatonin. Here in this study, we showed that when compared with the white light control group, white LED light exposure resulted in loss of yellow pigmentation, decreased body length and locomotor activity, oxidant-antioxidant imbalance and decreased expressions of aanat2, mtnr1ba, and pax7 in zebrafish embryos. Histological analysis of this group revealed disorganization of the spaces among photoreceptor cells, decreased total retinal thickness and photoreceptor cell layer thickness compared with the control group. Artificial lighting pollution has the potential to become an important risk factor for different diseases including cancer especially for industrialized countries, therefore, more studies should be performed and necessary regulations should be made regarding this risk factor.