Carnitine and/or Acetylcarnitine Deficiency as a Cause of Higher Levels of Ammonia

Maldonado, Cecilia; Guevara, Natalia; Queijo, Cecilia; González, Raquel; Fagiolino, Pietro; Vázquez, Marta

doi:10.1155/2016/2920108

Cited by 39 publications

(36 citation statements)

References 39 publications

(45 reference statements)

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“… 4 , 5 The prevalence of symptomatic hyperammonemia caused by VPA is unknown, and the condition is thought to be rare in adults. However, in a study carried out by our group, 6 almost one-third of adult patients (8 of 28 patients) developed ammonia levels higher than the reference range, although only one of these patients exhibited unequivocal symptoms (encephalopathy). L-Carnitine (LCAR) is commonly used as an antidote in acute intoxication with VPA, 7 but its use in chronic treatment is reserved for the pediatric setting.…”

Section: Introductionmentioning

confidence: 62%

L-Carnitine supplementation to reverse hyperammonemia in a patient undergoing chronic valproic acid treatment: A case report

et al. 2017

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Valproic acid is a broad-spectrum anticonvulsant that has also gained attention in the psychiatric setting. With respect to safety, valproic acid may induce a seemingly rare condition, hyperammonemia, which can induce a wide variety of symptoms ranging from irritability to coma. The proposed mechanism of hyperammonemia involves depletion of carnitine and overproduction of a toxic metabolite, 4-en-valproic acid, both of which impair the urea cycle and thus ammonia elimination. Carnitine is a commonly used antidote for acute intoxication of valproic acid, but is not a therapeutic option for management of chronic adults with adverse effects related to valproic acid. We herein report a case involving a woman with epilepsy who developed hyperammonemia after a change in her anticonvulsant therapy. She reported increased seizures and gastrointestinal disturbances. Her ammonia, valproic acid, 4-en-valproic acid, and carnitine levels were monitored. Her ammonia level was elevated and her carnitine level was at the inferior limit of the population range. She was supplemented with carnitine at 1 g/day. After 1 month, her ammonia level decreased, her carnitine level increased, and her seizures were better controlled. Carnitine supplementation was useful for reversal of her hyperammonemia, allowing her to continue valproic acid for seizure control.

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Section: Introductionmentioning

confidence: 62%

L-Carnitine supplementation to reverse hyperammonemia in a patient undergoing chronic valproic acid treatment: A case report

et al. 2017

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“…Acetylcarnitine performs major functions as a cofactor for the transport of long-chain fatty acids through the mitochondrial membrane [38]. However, previous research has demonstrated that acetylcarnitine deficiency leads to increased ammonia levels in the body [39]. Our former research has also proved that the expression a hepatic protein (histidine ammonia-lyase, HAL) involved in ammonia elimination was increased in sheep under OG conditions [4].…”

Section: Discussionmentioning

confidence: 87%

Comparative metabolome analysis of serum changes in sheep under overgrazing or light grazing conditions

Zhang

Gao

Guo

et al. 2019

Preprint

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Background Overgrazing is a primary contributor to severe reduction in forage quality and production in Inner Mongolia, leading to extensive ecosystem degradation, sheep health impairment and growth performance reduction. Further studies to identify serum biomarkers that reflect changes in sheep health and nutritional status following overgrazing would be beneficial. We hereby hypothesize that reduced sheep growth performance under overgrazing conditions would be associated with metabolic and immune response alterations. This study used an untargeted metabolomics analysis by conducting ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) of sheep serum under overgrazing and light grazing conditions to identify metabolic disruptions in response to overgrazing. Results The sheep body weight gains as well as serum biochemical variables associated with immune responses and nutritional metabolism (immunoglobulin G, albumin, glucose, and nonesterified fatty acids) were significantly decreased with overgrazing compared with light grazing condition. In contrast, other serum parameters such as alanine and aspartate aminotransferase, alkaline phosphatase, total bilirubin, blood urea nitrogen, and interleukin-8 were markedly higher in the overgrazing group. Principal component analysis discriminated the metabolomes of the light grazing from the overgrazing group. Multivariate and univariate analyses revealed changes in the serum concentrations of 15 metabolites (9 metabolites exhibited a marked increase, whereas 6 metabolites showed a significant decrease) in the overgrazing group. Major changes of fatty acid oxidation, bile acid biosynthesis, and purine and protein metabolism were observed. Conclusions These findings offer metabolic evidence for putative biomarkers for overgrazing-induced changes in serum metabolism. Target-identification of these particular metabolites may potentially increase our knowledge of the molecular mechanisms of altered immune responses, nutritional metabolism, and reduced sheep growth performance under overgrazing conditions.

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“…Ammonia levels in some of these patients were higher than the upper limit of the normal range in blood (25-94 μg/dL). Our research group has been studying increased ammonia levels in patients under VPA treatment [32,33]. High levels of ammonia in the brain can be the cause of seizures as ammonia easily crosses the blood-brain barrier, and in the brain, it can conjugate with α-ketoglutarate to form glutamate.…”

Section: Resultsmentioning

confidence: 99%

Active Pharmacovigilance in Epileptic Patients: A Deep Insight into Phenytoin Behaviour

Vázquez¹,

Fagiolino²,

Maldonado³

et al. 2019

Pharmacovigilance

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Despite the introduction of new and more expensive anticonvulsant drugs, phenytoin (PHT) is still a first-line medication for common types of epilepsy such as tonic-clonic and complex partial seizures but not for absence seizures. PHT shows a nonlinear kinetics and a narrow therapeutic range, thus a fine balance must be found between efficacy and toxic effects. Since the free (unbound) drug is responsible for producing the pharmacological effect, the concentration in a novel biological fluid more closely related to arterial free plasma drug concentrationsaliva-is used in this study as part of the monitoring strategy. Therefore, in order to optimize therapy in epileptic patients under PHT treatment, plasma and saliva concentrations of PHT were measured, and adverse drug reactions were registered during a 2-year follow-up. CYP2C9, CYP2C19, and epoxide hydrolase polymorphisms (enzymes involved in PHT metabolism) were also analyzed using, in this way, pharmacogenetics for drug safety. The two PHT brands commercially available in our country and used in this study demonstrated similar pattern of efficacy and safety.

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Carnitine and/or Acetylcarnitine Deficiency as a Cause of Higher Levels of Ammonia

Cited by 39 publications

References 39 publications

L-Carnitine supplementation to reverse hyperammonemia in a patient undergoing chronic valproic acid treatment: A case report

L-Carnitine supplementation to reverse hyperammonemia in a patient undergoing chronic valproic acid treatment: A case report

Comparative metabolome analysis of serum changes in sheep under overgrazing or light grazing conditions

Active Pharmacovigilance in Epileptic Patients: A Deep Insight into Phenytoin Behaviour

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