Neuroprotective effects of L-carnitine towards oxidative stress and inflammatory processes: a review of its importance as a therapeutic drug in some disorders.

L-carnitine (LC) is a natural compound crucial for transporting long-chain fatty acids into mitochondria for ATP production. It is found mainly in red meat, fish, and dairy products, in addition to being synthesized by the body. LC is supplemented in patients with organic acidemias since it corrects secondary carnitine deficiency and accelerates the removal of the accumulated acyl organic acid derivative groups.

L-carnitine protects against oxidative damage and neuroinflammation in cerebral cortex of rats submitted to chronic chemically-induced model of hyperphenylalaninemia.

Phenylketonuria is a genetic disorder characterized by high phenylalanine levels, the main toxic metabolite of the disease. Hyperphenylalaninemia can cause neurological impairment. In order to avoid this symptomatology, patients typically follow a phenylalanine-free diet supplemented with a synthetic formula that provides essential amino acids, including L-carnitine.

Neurodegenerative biomarkers and inflammation in patients with propionic and methylmalonic acidemias: effect of L-carnitine treatment.

Propionic and methylmalonic acidemias (PAcidemia and MMAcidemia, respectively) are genetic disorders characterized by acute metabolic decompensation and neurological complications. L-carnitine (LC) is effective in reducing toxic metabolites that are related to the pathophysiology of these diseases. Therefore we investigated biomarkers of inflammation (cytokines and C-reactive protein (CRP)), neurodegeneration (BDNF, NCAM-1 and cathepsin-D) and biomolecules oxidation (sulfhydryl content and thiobarbituric acid-reactive species (TBARS)), as well as carnitine concentrations in untreated patients with PAcidemia and MMAcidemia, in patients under treatment with LC and a protein-restricted diet for until 2 years and in patients under the same treatment for more than 2 years.

Inflammation and lipoperoxidation in mucopolysaccharidoses type II patients at diagnosis and post-hematopoietic stem cell transplantation.

Introduction: Mucopolysaccharidosis type II (MPS II) is caused by deficiency of the enzyme iduronate-2-sulfatase; one possible therapy for MPS II is hematopoietic stem cell transplantation (HSCT). It is established that there is excessive production of reactive species in MPS II patients, which can trigger several processes, such as the inflammatory cascade.

Objectives: Our aim was to outline an inflammatory profile and lipoperoxidation of MPS II patients for a better understanding of disease and possible benefits that HSCT can bring in these processes.

Long-term enzyme replacement therapy in Fabry patients protects against oxidative and inflammatory process.

Fabry disease (FD) is an X-linked recessive lysosomal storage disorder, characterized by a deficiency of α-galactosidase, which causes the progressive accumulation of glycosphingolipids, especially globotriaosylsphingosine (Gb3), in lysosomes across multiple organs. Substrate deposition, associated with tissue damage in FD, also contributes to the emergence of a pro-inflammatory state presented by some patients. We investigated pro- and anti-inflammatory cytokines, and the expression of inflammation-associated genes in treated FD patients, as well as oxidative parameters.

Effect of genistein and coenzyme Q10 in oxidative damage and mitochondrial membrane potential in an attenuated type II mucopolysaccharidosis cellular model.

Mucopolysaccharidosis type II (MPS II) is an inborn error of the metabolism resulting from several possible mutations in the gene coding for iduronate-2-sulfatase (IDS), which leads to a great clinical heterogeneity presented by these patients. Many studies demonstrate the involvement of oxidative stress in the pathogenesis of inborn errors of metabolism, and mitochondrial dysfunction and oxidative stress can be related since most of reactive oxygen species come from mitochondria. Cellular models have been used to study different diseases and are useful in biochemical research to investigate them in a new promising way.

Increased peripheral of brain-derived neurotrophic factor levels in phenylketonuric patients treated with l-carnitine.

Phenylketonuria (PKU) is the most common inherited metabolic disorders caused by severe deficiency or absence of phenylalanine hydroxylase activity that converts phenylalanine (Phe) to tyrosine. PKU patients were treated with a Phe restricted diet supplemented with a special formula containing l-carnitine (L-car), well-known antioxidant compound. The lack of treatment can cause neurological and cognitive impairment, as severe mental retardation, neuronal cell loss and synaptic density reduction.

Alterations of Plasmatic Biomarkers of Neurodegeneration in Mucopolysaccharidosis Type II Patients Under Enzyme Replacement Therapy.

Mucopolysaccharidosis type II (MPS II) is a disorder caused by a deficient activity of iduronate-2-sulfatase, a lysosomal enzyme responsible for degrading glycosaminoglycans (GAGs). The abnormal storage of GAGs within lysosomes disrupts cellular homeostasis and leads to a severe symptomatology. Patients present neuropsychiatric impairment characterized by mental retardation and impaired cognition.

Treatment of maple syrup urine disease: Benefits, risks, and challenges of liver transplantation.

Maple syrup urine disease (MSUD) is caused by a deficiency in the activity of the branched-chain α-ketoacid dehydrogenase (BCKD) complex, promoting the accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, as well as their respective α-keto acids. MSUD is an autosomal recessive hereditary metabolic disorder characterized by ketoacidosis, ataxia, coma, and mental and psychomotor retardation. The mechanisms involved in the brain damage caused by MSUD are not fully understood.

Increased cytokine levels induced by high phenylalanine concentrations in late diagnosis PKU patients compared to early diagnosis: Anti-inflammatory effect of L-carnitine.

Phenylketonuria (PKU) was the first genetic disease to have an effective therapy, which consists of phenylalanine intake restriction. However, there are patients who do not adhere to treatment and/or are not submitted to neonatal screening. PKU patients present L-carnitine (L-car) deficiency, compound that has demonstrated an antioxidant and anti-inflammatory role in metabolic diseases.

Evaluation of biochemical profile and oxidative damage to lipids and proteins in patients with lysosomal acid lipase deficiency.

Lysosomal acid lipase deficiency (LALD) is an inborn error of metabolism that lacks satisfactory treatment, which leads to the development of severe hepatic and cardiac complications and may even lead to death. In this sense, knowledge of the mechanisms involved in the pathophysiology of this disorder becomes essential to allow the search for new therapeutic strategies. There are no studies in the literature investigating the role of reactive species and inflammatory processes in the pathophysiology of this disorder.

Inflammatory process and oxidative/nitrative stress: in vivo study in mucopolysaccharidosis type IV A patients under long-term enzyme replacement therapy.

Mucopolysaccharidosis type IV A (MPS IVA) is an inborn error of the metabolism (IEM) caused by a deficiency of the enzyme N-acetylgalactosamine 6-sulfate sulfatase (GALNS). Since 2014, enzyme replacement therapy (ERT) is the recommended treatment for these patients. It is known that the inflammatory response is closely related to antioxidant defenses and oxidative stress, and literature shows involvement of oxidative stress in the pathogenesis of IEM.

Evaluation of oxidative damage to biomolecules and inflammation in patients with urea cycle disorders.

Urea cycle disorders (UCD) are inborn errors of metabolism that occur due to a loss of function in enzymes and transporters involved in the urea cycle, causing an intoxication by hyperammonemia and accumulation of metabolites. Patients can develop hepatic encephalopathy (HE), severe neurological and motor disabilities, and often death. The mechanisms involved in the pathophysiology of UCD are many and complex, but there are strong indications that oxidative stress and inflammation are present, being responsible for at least part of the cellular damage that occurs in these diseases.

Molecular profile and peripheral markers of neurodegeneration in patients with Niemann-Pick type C: Decrease in Plasminogen Activator Inhibitor type 1 and Platelet-Derived Growth Factor type AA.

Niemann-Pick type C1 (NPC1) is a fatal inherited disease, caused by pathogenic variants in NPC1 gene, which leads to intracellular accumulation of non-esterified cholesterol and glycosphingolipids. This accumulation leads to a wide range of clinical manifestations, including neurological and cognitive impairment as well as psychiatric disorders. The pathophysiology of cerebral damage involves loss of Purkinje cells, synaptic disturbance, and demyelination.

Clinical findings of patients with hyperammonemia affected by urea cycle disorders with hepatic encephalopathy.

Urea cycle disorders (UCD) are a group of genetic diseases caused by deficiencies in the enzymes and transporters involved in the urea cycle. The impairment of the cycle results in ammonia accumulation, leading to neurological dysfunctions and poor outcomes to affected patients. The aim of this study is to investigate and describe UCD patients' principal clinical and biochemical presentations to support professionals on urgent diagnosis and quick management, aiming better outcomes for patients.

Evaluation of oxidative stress and mitochondrial function in a type II mucopolysaccharidosis cellular model: in vitro effects of genistein and coenzyme Q10.

Mucopolysaccharidosis type II (MPS II or Hunter Syndrome) is a lysosomal disease caused by deficient degradation of glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate due to the deficiency of the enzyme iduronate-2-sulfatase. The main treatment for MPS II is the administration of the recombinant form of the enzyme, in a process known as enzyme replacement therapy (ERT). Oxidative damage can contribute to the pathophysiology of MPS II and treatment with ERT can reduce the effects of oxidative stress.

Parameters of Oxidative Stress and Behavior in Animals Treated with Dexametasone and Submitted to Pentylenetetrazol Kindling.

Background And Purpose: Oxidative stress (OS) is defined as an excessive production of reactive oxygen species that cannot be neutralized by the action of antioxidants, but also as an alteration of the cellular redox balance. The relationship between OS and epilepsy is not yet fully understood. The objective of this study was to evaluate the effect of dexamethasone on OS levels and memory in the kindling model induced by pentylenetetrazole.

Hyperammonemia in Inherited Metabolic Diseases.

Ammonia is a neurotoxic compound which is detoxified through liver enzymes from urea cycle. Several inherited or acquired conditions can elevate ammonia concentrations in blood, causing severe damage to the central nervous system due to the toxic effects exerted by ammonia on the astrocytes. Therefore, hyperammonemic patients present potentially life-threatening neuropsychiatric symptoms, whose severity is related with the hyperammonemia magnitude and duration, as well as the brain maturation stage.

Protective effects of L-carnitine on behavioral alterations and neuroinflammation in striatum of glutaryl-COA dehydrogenase deficient mice.

Glutaric acidemia type 1 (GA1) is caused by glutaryl-CoA dehydrogenase deficiency that leads to a blockage in the metabolic route of the amino acids lysine and tryptophan and subsequent accumulation of glutaric acid (GA), 3-hydroxyglutaric acids and glutarylcarnitine (C5DC). Patients predominantly manifest neurological symptoms, associated with acute striatal degeneration, as well as progressive cortical and striatum injury whose pathogenesis is not yet fully established. Current treatment includes protein/lysine restriction and l-carnitine supplementation of (L-car).

Preliminary results of PBA-loaded nanoparticles development and the effect on oxidative stress and neuroinflammation in rats submitted to a chemically induced chronic model of MSUD.

Maple syrup urine disease (MSUD) is a genetic disorder that leads the accumulation of branched-chain amino acids (BCAA) leucine (Leu), isoleucine, valine and metabolites. The symptomatology includes psychomotor delay and mental retardation. MSUD therapy comprises a lifelong protein strict diet with low BCAA levels and is well established that high concentrations of Leu and/or its ketoacid are associated with neurological symptoms.

Disruption of mitochondrial functions and oxidative stress contribute to neurologic dysfunction in organic acidurias.

Organic acidurias (OADs) are inherited disorders of amino acid metabolism biochemically characterized by accumulation of short-chain carboxylic acids in tissues and biological fluids of the affected patients and clinically by predominant neurological manifestations. Some of these disorders are amenable to treatment, which significantly decreases mortality and morbidity, but it is still ineffective to prevent long-term neurologic and systemic complications. Although pathogenesis of OADs is still poorly established, recent human and animal data, such as lactic acidosis, mitochondrial morphological alterations, decreased activities of respiratory chain complexes and altered parameters of oxidative stress, found in tissues from patients and from genetic mice models with these diseases indicate that disruption of critical mitochondrial functions and oxidative stress play an important role in their pathophysiology.

Clinical, biochemical and molecular findings of 24 Brazilian patients with glutaric acidemia type 1: 4 novel mutations in the GCDH gene.

Glutaric aciduria type 1 (GA-1) is a rare but treatable inherited disease caused by deficiency of glutaryl-CoA dehydrogenase activity due to GCDH gene mutations. In this study, we report 24 symptomatic GA-1 Brazilian patients, and present their clinical, biochemical, and molecular findings. Patients were diagnosed by high levels of glutaric and/or 3-hydroxyglutaric and glutarylcarnitine.