RESUMO
Neurodegenerative diseases (ND) are characterised by loss of neurons in the brain and spinal cord. For the normal functioning of the brain, divers group of fatty acids in the form of glycerophospholipids, glycerol ether lipids, cerebrosides, sulfatides, and gangliosides are essential. They are present abundantly in the nervous system and are actively involved in both the development and maintenance of the nervous system. A dietary deficiency of essential fatty acid during development results in hypomyelination state which affects various neuronal functions. Several studies suggested that age remains the primary risk factor for almost all neurodegenerative disorders. The potential contribution of these fatty acids in the progression of neurodegenerative disorders is indispensable. Erucic acid an omega 9 fatty acid, which is obtained from edible oils has proven to cause myocardial lipidosis, heart lesions and hepatic steatosis in animals therefore, its content in edible oils is restricted to certain levels by regulatory agencies. However, erucic acid in the form of a mixture with oleic acid is often used as a dietary treatment for the management of adrenoleukodystrophy without any cardiotoxicity. Our literature search revealed that, erucic acid reported to enhance cognitive function, interact with peroxisome proliferator activated receptors (PPARs), inhibit elastase and thrombin. In this review first we have attempted to describe the relationship between fatty acids and neurodegeneration followed by a description on the pharmacology of erucic acid. The overall purpose of this review is to analyse toxic and beneficial neuropharmacological effects of erucic acid.
Assuntos
Ácidos Erúcicos , Ácidos Graxos , Animais , Dieta , Ácidos Erúcicos/análise , Ácidos Erúcicos/uso terapêutico , Ácido Oleico , Óleos de PlantasRESUMO
Osteoporosis is associated with increase in fat tissue in bone marrow in humans. Mesenchymal stem cells in bone marrow are induced to differentiate into osteoblasts rather than adipocytes by the stimulation of peroxisome proliferator-activated receptor (PPAR) γ antagonists. PPARγ antagonists are expected to be useful to prevent osteoporosis by regulating the lineages of mesenchymal stem cells in bone marrow, as well as the prevention of obesity. In this study, we explored natural components suppressing PPARγ transcriptional activity in rosemary. Separation of active fraction of rosemary extract by repeated high performance liquid chromatograph and PPARγ luciferase reporter assay identified erucic acid, one of the monounsaturated fatty acids, as an active component. Twenty-five-micrometer erucic acid significantly decreased PPARγ luciferase activity and enhanced the differentiation of mouse-delivered C3H10T1/2 cells into osteoblasts rather than adipocytes. Furthermore, 25-µM erucic acid significantly decreased the expression of adipocyte marker genes, while accelerating osteoblast marker genes. In conclusion, erucic acid is a novel natural component derived from rosemary regulating mesenchymal stem cell differentiation via suppression of PPARγ transcriptional activity.
Assuntos
Adipócitos/metabolismo , Ácidos Erúcicos/uso terapêutico , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , PPAR gama/efeitos dos fármacos , Extratos Vegetais/química , Rosmarinus/química , Animais , Diferenciação Celular , Ácidos Erúcicos/farmacologia , Humanos , Camundongos , PPAR gama/metabolismoRESUMO
In this study, we investigated a potent acetylcholinesterase inhibitor that was isolated from radish leaf (Raphanus sativus L.) extracts. Through sequential fractionation of radish leaf extract, the active constituent was identified as cis-13-docosenamide (erucamide). To validate the potency, erucamide derived from radish leaves was supplemented in diets and then fed to trimethyltin (TMT)-exposed mice. Specifically, mice had free access to a control diet or diets containing different concentrations of erucamide for 3 weeks, followed by an injection of TMT (2.5 mg/kg body weight). Our results showed that pretreatment of mice with erucamide (20 and 40 mg/kg body weight per day) significantly attenuated the TMT-induced learning and memory deficits that were assessed by Y-maze and passive avoidance tests. These findings suggest that radish leaves, and possibly its isolated erucamide, may have preventive effects against memory deficits related to Alzheimer's disease by modulation of cholinergic functions.
Assuntos
Inibidores da Colinesterase/farmacologia , Ácidos Erúcicos/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Raphanus , Animais , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/uso terapêutico , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Erúcicos/administração & dosagem , Ácidos Erúcicos/uso terapêutico , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Camundongos Endogâmicos ICR , Fitoterapia , Folhas de Planta , Compostos de TrimetilestanhoRESUMO
This is a case report of adrenomyeloneuropathy (AMN), the adult variant of adrenoleukodystryphy (ALD). The diagnoses in the patient, aged 34, was confirmed via increased serum very long chain fatty acid concentration (VLCFA). Treatment started with the cholesterol lowering drug, atorvastatin, followed by add-on therapy with Lorenzo's oil (LO) and finally supplementation with docosahexaenoic acid (DHA). The magnetic resonance imaging (MRI) scan of the AMN patient before DHA treatment, already showed abnormal white matter in the brain. Although the MRI showed no neurological improvement after 6 months of DHA treatment, no selective progression of demyelination was detected in the AMN patient. Contrary to what was expected, LO failed to sustain or normalize the VLCFA levels or improve clinical symptoms. It was however, shown that DHA supplementation in addition to LO, increased DHA levels in both plasma and red blood cells (RBC). Additionally, the study showed evidence that the elongase activity in the elongation of eicosapentaenoic acid (EPA) to docosapentaenoic acid (DPA) might have been significantly compromised, due to the increased DHA levels.
Assuntos
Adrenoleucodistrofia/dietoterapia , Adrenoleucodistrofia/tratamento farmacológico , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácidos Erúcicos/uso terapêutico , Hipolipemiantes/uso terapêutico , Trioleína/uso terapêutico , Adrenoleucodistrofia/sangue , Adrenoleucodistrofia/fisiopatologia , Adulto , Anticolesterolemiantes/uso terapêutico , Atorvastatina , Terapia Combinada , Progressão da Doença , Ácidos Docosa-Hexaenoicos/sangue , Combinação de Medicamentos , Quimioterapia Combinada , Ácidos Heptanoicos/uso terapêutico , Humanos , Masculino , Pirróis/uso terapêutico , Resultado do TratamentoRESUMO
We treated a girl with Zellweger syndrome using a special infant formula supplemented with middle chain triglyceride (MCT) milk, docosahexaenoic acid (DHA), Lorenzo's oil, and Lunaria oil, which is rich in nervonic acid (C24:1). We examined the fatty acid contents of the plasma and red blood cell (RBC) membrane. Neurological development was evaluated using Denver developmental screening test and auditory brainstem response (ABR). Her delayed neurological development, liver dysfunction, and cholestasis were all improved 2 weeks after starting the dietary treatment. DHA level in RBC membranes was increased and very long chain fatty acid (VLCFA,C26:0) levels were decreased. Our findings suggest that the dietary treatment with combination of MCT milk, DHA, Lorenzo's oil, and Lunaria oil in the patients with Zellweger syndrome bring some benefits for neurological development.
Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácidos Erúcicos/uso terapêutico , Trioleína/uso terapêutico , Síndrome de Zellweger/dietoterapia , Síndrome de Zellweger/fisiopatologia , Desenvolvimento Infantil/fisiologia , Combinação de Medicamentos , Quimioterapia Combinada , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Ácidos Graxos/sangue , Feminino , Humanos , Recém-Nascido , Resultado do Tratamento , Triglicerídeos/uso terapêuticoRESUMO
Most of the studies indicate that there is as yet no complete cure for X-ALD. However, methods of the treatment seem to slow rather than treat the disease. One method is the use of Lorenzo's oil in conjunction with a low fat diet, which may help in cerebral X-ALD. X-ALD is in very close resemblance to another neurodegenerative disease, amyotrophic lateral sclerosis (ALS). One of the believed pathomechanisms of ALS is oxidative stress; therefore, this article's emphasis on the role of reactive oxygen species in X-ALD. The aim of the present study was to review the literature concerning the advances in the treatment of X-adrenoleukodystrophy (X-ALD, OMIM # 300100) in the last two decades and to shed more light on the link between oxidative stress and X-ALD. This review article may point to a deficit in reactive oxygen species (ROS) scavenging and/or ROS overproduction being involved in the aetiopathology of these neurodegenerative diseases. Consequently, one of the useful neuronal rescue strategies could be the treatment with antioxidant agents.
Assuntos
Adrenoleucodistrofia/terapia , Antioxidantes/uso terapêutico , Ácidos Erúcicos/uso terapêutico , Estresse Oxidativo , Espécies Reativas de Oxigênio , Trioleína/uso terapêutico , Adrenoleucodistrofia/metabolismo , Esclerose Lateral Amiotrófica/terapia , Animais , Combinação de Medicamentos , Sequestradores de Radicais Livres/uso terapêutico , HumanosRESUMO
OBJECTIVES: This review focuses on the dietary treatment of four neuropediatric disorders: 1) X-linked adrenoleukodystrophy (X-ALD); 2) attention deficit disorders (ADD); 3) refractory epilepsy; and 4) inborn errors of metabolism. DEVELOPMENT: The use of Lorenzo's oil in the treatment of X-ALD has been controversial since no clear efficacy has been demonstrated because of a lack of controlled studies. Although this treatment normalizes the levels of very-long chain fatty acids in children with the cerebral form of X-ALD, the neurological symptoms persist or progress. The dietary treatment of ADD with or without hyperactivity consists of elimination diets such as the Feingold diet and megavitamins. Although the results of several controlled studies are contradictory, there is no scientific evidence that sugar, artificial food colorings or sweeteners are responsible for behavior or learning problems in children. The ketogenic diet has been effective for the control of refractory epilepsy such as infantile spasms and myoclonic seizures. Important side effects include gastrointestinal complaints, metabolic complications, poor growth and nutrition, liver abnormalities and renal calculi. The early identification and treatment of inborn errors of metabolism require prompt diagnosis and correction of metabolic abnormalities. Restriction of protein and fats may be necessary in certain neurometabolic disorders. A variety of special formulas is available to meet the nutritional requirements and avoid offending substances in neurometabolic patients. CONCLUSIONS: Dietary treatment plays an important role in the management of certain neuropediatric disorders, such as the use of special formulas in inborn errors of metabolism and the ketogenic diet in refractory epilepsy. The efficacy of Lorenzo's oil in the cerebral form of X-ALD and of the elimination of artificial food colorings and sweeteners in ADD remain to be proved.
Assuntos
Adrenoleucodistrofia/terapia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Dieta , Epilepsia/terapia , Erros Inatos do Metabolismo/terapia , Adrenoleucodistrofia/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Combinação de Medicamentos , Epilepsia/fisiopatologia , Ácidos Erúcicos/uso terapêutico , Humanos , Erros Inatos do Metabolismo/fisiopatologia , Trioleína/uso terapêuticoRESUMO
Clinically, peroxisome biogenesis disorders (PBDs) are a group of lethal diseases with a continuum of severity of clinical symptoms ranging from the most severe form, Zellweger syndrome, to the milder forms, infantile Refsum disease and rhizomelic chondrodysplasia punctata. PBDs are characterised by a number of biochemical abnormalities including impaired degradation of peroxide, very long chain fatty acids, pipecolic acid, phytanic acid and xenobiotics and impaired synthesis of plasmalogens, bile acids, cholesterol and docosahexaenoic acid. Treatment of PBD patients as a group is problematic since a number of patients, especially those with Zellweger syndrome, have significant neocortical alterations in the brain at birth so that full recovery would be impossible even with postnatal therapy. To date, treatment of PBD patients has generally involved only supportive care and symptomatic therapy. However, the fact that some of the milder PBD patients live into the second decade has prompted research into possible treatments for these patients. A number of experimental therapies have been evaluated to determine whether or not correction of biochemical abnormalities through dietary supplementation and/or modification is of clinical benefit to PBD patients. Another approach has been pharmacological induction of peroxisomes in PBD patients to improve overall peroxisomal biochemical function. Well known rodent peroxisomal proliferators were found not to induce human peroxisomes. Recently, our laboratory demonstrated that sodium 4-phenylbutyrate induces peroxisome proliferation and improves biochemical function (very long chain fatty acid beta-oxidation rates and very long chain fatty acid and plasmalogens levels) in fibroblast cell lines from patients with milder PBD phenotypes. Dietary supplementation and/or modification and pharmacological induction of peroxisomes as treatment strategies for PBD patients will be the subject of this review.
Assuntos
Antineoplásicos/farmacologia , Suplementos Nutricionais , Ácidos Erúcicos/uso terapêutico , Transtornos Peroxissômicos/tratamento farmacológico , Fenilbutiratos/farmacologia , Trioleína/uso terapêutico , Síndrome de Zellweger/tratamento farmacológico , Combinação de Medicamentos , Humanos , Transtornos Peroxissômicos/dietoterapia , Transtornos Peroxissômicos/terapia , Síndrome de Zellweger/dietoterapiaRESUMO
The demonstration of abnormal levels of fatty acids or plasmalogens in plasma or red blood cells is key to the diagnosis of peroxisomal disorders. We report the levels of 62 fatty acids and plasmalogens in patients with X-linked adrenoleukodystrophy (X-ALD), Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD), both at baseline and after dietary interventions. "Lorenzo's Oil" therapy in X-ALD normalizes the levels of saturated very long chain fatty acids in plasma, but leads to reduced levels of omega 6 and other omega 3 fatty acids, and requires monitoring and appropriate dietary supplements. Patients with ZS, NALD and IRD have reduced levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) which can be normalized by the oral administration of microencapsulated DHA and AA.
Assuntos
Eritrócitos/metabolismo , Ácidos Graxos/sangue , Transtornos Peroxissômicos/sangue , Adolescente , Adulto , Criança , Pré-Escolar , Cromatografia Gasosa , Gorduras Insaturadas na Dieta/uso terapêutico , Combinação de Medicamentos , Ácidos Erúcicos/uso terapêutico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Transtornos Peroxissômicos/dietoterapia , Trioleína/uso terapêuticoRESUMO
The fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient whose diet was supplemented with Lorenzo's oil (glycerol trioleate and glycerol trierucate) for 9 months was determined. The diet depressed plasma and liver saturated very long chain fatty acids (24:0 and 26:0) and increased plasma and liver erucic (22:1) and nervonic (24:1) acids. The levels of plasma linoleic (18:2 n-6), eicosopentaenoic (20:5 n-3), and docosahexaenoic (22:6 n-3) acids were also reduced, while the biochemical marker for essential fatty acid deficiency (20:3 n-9) was markedly increased in liver. However, we were unable to detect any corresponding changes in brain indicating that little erucic acid crossed the blood-brain barrier. Our findings suggest that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy.