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SUMMARY: Cadmium (Cd) is a toxic element that accumulates in kidney and liver. L-carnitine(LC) is a natural compound that has been shown to exhibit antioxidant activity. Aim of this study was to investigate the effect of L-carnitine against cadmium-induced changes in liver and kidney tissues in prepubertal female rats. In this study 21-day-old female Wistar Albino rats were used. Control, cadmium (2 mg/kg cadmium intraperitoneally), L-carnitine (300 mg/kg orally) and cadmium+L-carnitine groups were formed. Liver and kidney tissue sections were stained with Hematoxylin-Eosin and Masson Trichrome. Histological scoring was performed in liver and kidney. In the liver tissue given Cd, bile duct proliferation, inflammation cells and connective tissue in the portal area were decreased in treatment group. In kidneys, cadmium group treated with L-carnitine, it was observed that the capillary congestion in the kidneys decreased, but tubular dilatation continued in some places. In fibrosis scoring of the liver groups,statistically significant decrease was observed in the Cd+LC group compared to group of cadmium. In the histological scoring results of the kidney groups, statistically significant decrease in congestion and tubular epithelial degeneration was observed in the group treated with L-carnitine compared to group with cadmium. In conclusion medium-dose cadmium has toxic effects in liver and kidney of prepubertal female rats in subacute period,these effects are alleviated with L-carnitine.
El cadmio (Cd) es un elemento tóxico que se acumula en los riñones y el hígado. La L-carnitina (LC) es un compuesto natural que ha demostrado tener actividad antioxidante. El objetivo de este estudio fue investigar el efecto de la L-carnitina contra los cambios inducidos por el cadmio en los tejidos del hígado y el riñón en ratas hembra prepúberes. En este estudio se utilizaron ratas Wistar Albinas hembra de 21 días de edad. Se formaron grupos control, cadmio (2 mg/kg de cadmio por vía intraperitoneal), L- carnitina (300 mg/kg por vía oral) y cadmio + L-carnitina. Se tiñeron secciones de tejido de hígado y riñón con Hematoxilina-Eosina y tricrómico de Masson. La puntuación histológica se realizó en hígado y riñón. En el tejido hepático que recibió Cd, la proliferación de los conductos biliares, las células inflamatorias y el tejido conectivo en el área portal disminuyeron en el grupo con tratamiento. En los riñones, en el grupo de cadmio tratado con L- carnitina, se observó que la congestión capilar disminuyó, pero la dilatación tubular continuó en algunos sitios. En la puntuación de fibrosis de los grupos de hígado, se observó una disminución estadísticamente significativa en el grupo de Cd+LC en comparación con el grupo de cadmio. Los resultados de puntuación histológica de los grupos de riñón, arrojó una disminución estadísticamente significativa en la congestión y el epitelio tubular Se observó degeneración en el grupo tratado con L-carnitina en comparación con el grupo con cadmio. En conclusión, las dosis medias de cadmio tienen efectos tóxicos en el hígado y los riñones de ratas hembras prepúberes en el período subagudo; estos efectos se alivian con L-carnitina.
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Animais , Feminino , Ratos , Cádmio/toxicidade , Carnitina/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ratos WistarRESUMO
L-Acetylcarnitine (ALC), a versatile compound, has demonstrated beneficial effects in depression, Alzheimer's disease, cognitive impairment, and other conditions. This study focuses on its antithyroid activity. The precursor molecule, L-carnitine, inhibited the uptake of triiodothyronine (T3) and thyroxine (T4), and it is possible that ALC may reduce the iodination process of T3 and T4. Currently, antithyroid drugs are used to control the excessive production of thyroid hormones (TH) through various mechanisms: (i) forming electron donor-acceptor complexes with molecular iodine, (ii) eliminating hydrogen peroxide, and (iii) inhibiting the enzyme thyroid peroxidase. To understand the pharmacological properties of ALC, we investigated its plausible mechanisms of action. ALC demonstrated the ability to capture iodine (Kc = 8.07 ± 0.32 x 105 M-1), inhibit the enzyme lactoperoxidase (LPO) (IC50 = 17.60 ± 0.76 µM), and scavenge H2O2 (39.82 ± 0.67 mM). A comprehensive physicochemical characterization of ALC was performed using FTIR, Raman, and UV-Vis spectroscopy, along with theoretical DFT calculations. The inhibition process was assessed through fluorescence spectroscopy and vibrational analysis. Docking and molecular dynamics simulations were carried out to predict the binding mode of ALC to LPO and to gain a better understanding into the inhibition process. Furthermore, albumin binding experiments were also conducted. These findings highlight the potential of ALC as a therapeutic agent, providing valuable insights for further investigating its role in the treatment of thyroid disorders.
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Iodo , Glândula Tireoide , Lactoperoxidase/metabolismo , Lactoperoxidase/farmacologia , Acetilcarnitina/metabolismo , Acetilcarnitina/farmacologia , Peróxido de Hidrogênio/farmacologia , Iodo/química , Modelos TeóricosRESUMO
Background: L-2-hydroxyglutaric aciduria (L2HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by pathogenic variants in the L2HGDH gene which encodes mitochondrial 2-hydroxyglutarate dehydrogenase. Here, we report a case of L2HGA in a Mexican-Mayan patient with a homozygous mutation at L2HGDH gene and clinical response to vitamin supplements and levocarnitine. Case report: A 17-year-old, right-handed female patient with long-term history of seizures, developmental delay and ataxia was referred to a movement disorders specialist for the evaluation of tremor. Her brain MRI showed typical findings of L2HGA. The diagnosis was corroborated with elevated levels of 2-hydroxyglutaric acid in urine and genetic test which revealed a homozygous genetic known variant c.569C>T in exon 5 of L2HGDH gene. She was treated with levocarnitine and vitamin supplements, showing improvement in tremor and gait. Discussion: To our knowledge this is the first report of a Mexican patient with L2HGA. This case adds information about a rare condition in a different ethnic group and supports the findings of other authors which encountered symptomatic improvement with the use of flavin adenine dinucleotide (and its precursor riboflavin), and levocarnitine. Highlights: We report the first case of Mexican-Mayan patient with L2HGA showing a missense homozygous mutation in L2HGDH gene, and improvement of symptoms with vitamin supplements and levocarnitine.
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Encefalopatias Metabólicas Congênitas , Carnitina , Tremor , Humanos , Feminino , Adolescente , Mutação/genética , Vitaminas , Oxirredutases do Álcool/genéticaRESUMO
l-carnitine (LC) transports fatty acids to the mitochondria for energy production, reducing lipid availability for peroxidation through ß-oxidation. This research examines the effect of LC supplementation to two skimmed milk-based extenders on the cryosurvival of chilled (5°C) and frozen-thawed Peruvian Paso horse spermatozoa .An initial experiment determined the optimal LC concentration (0, 1, 5, 10, 25, and 50 mM) when added to INRA-96® and UHT (skimmed milk + 6% egg yolk) extenders, using nine ejaculates from three stallions chilled for up to 96 h. Subsequently, the effect of 25 mM LC supplementation (the optimal concentration) on chilling (INRA-96) and freezing (INRA-Freeze®) extenders was evaluated using eight pooled samples from sixteen ejaculates (2 ejaculates/pool) from four stallions. Results indicated that all LC concentrations produced significantly higher values (P<0.05) for kinematic variables (total [TM] and progressive motilities, curvilinear [VCL] and straight-line [VSL] velocity, and beat-cross frequency [BCF]), and the integrity of plasma/acrosome membranes (IPIA) compared to non-supplemented chilled sperm samples for up to 96 h with both extenders. Moreover, the use of 25 mM LC was more efficient (P<0.05) in preserving the post-chilled values of velocity, BCF, and IPIA for the long term than lower LC concentrations (1-10 mM). Post-thaw values of total motility, the amplitude of lateral head displacement (ALH), and IPIA were significantly improved (P<0.05) when INRA-Freeze extender was supplemented with 25 mM LC. In conclusion, supplementation of l-carnitine to skimmed milk-based extenders enhanced kinematic variables and protected the membrane integrity in chilled and frozen-thawed Peruvian Paso horse spermatozoa.
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Carnitina , Membrana Celular , Criopreservação , Crioprotetores , Preservação do Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Animais , Masculino , Cavalos , Preservação do Sêmen/métodos , Preservação do Sêmen/veterinária , Criopreservação/métodos , Criopreservação/veterinária , Espermatozoides/efeitos dos fármacos , Carnitina/farmacologia , Crioprotetores/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Congelamento , Fenômenos Biomecânicos/efeitos dos fármacosRESUMO
Obesity causes inflammation in the adipose tissue and can affect the central nervous system, leading to oxidative stress and mitochondrial dysfunction. Therefore, it becomes necessary to seek new therapeutic alternatives. Gold nanoparticles (GNPs) could take carnitine to the adipose tissue, thus increasing fatty acid oxidation, reducing inflammation, and, consequently, restoring brain homeostasis. The objective of this study was to investigate the effects of GNPs associated with carnitine on the neurochemical parameters of obesity-induced mice. Eighty male Swiss mice that received a normal lipid diet (control group) or a high-fat diet (obese group) for 10 weeks were used. At the end of the sixth week, the groups were divided for daily treatment with saline, GNPs (70 µg/kg), carnitine (500 mg/kg), or GNPs associated with carnitine, respectively. Body weight was monitored weekly. At the end of the tenth week, the animals were euthanized and the mesenteric fat removed and weighed; the brain structures were separated for biochemical analysis. It was found that obesity caused oxidative damage and mitochondrial dysfunction in brain structures. Treatment with GNPs isolated reduced oxidative stress in the hippocampus. Carnitine isolated decreased the accumulation of mesenteric fat and oxidative stress in the hippocampus. The combination of treatments reduced the accumulation of mesenteric fat and mitochondrial dysfunction in the striatum. Therefore, these treatments in isolation, become a promising option for the treatment of obesity.
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Encéfalo , Carnitina , Modelos Animais de Doenças , Ouro , Nanopartículas Metálicas , Obesidade , Estresse Oxidativo , Animais , Carnitina/farmacologia , Carnitina/administração & dosagem , Carnitina/uso terapêutico , Ouro/farmacologia , Masculino , Obesidade/tratamento farmacológico , Obesidade/patologia , Obesidade/complicações , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Dieta Hiperlipídica , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/patologia , Lesões Encefálicas/metabolismo , Peso Corporal/efeitos dos fármacosRESUMO
Abstract Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive inherited disorder related to lipid metabolism affecting skeletal muscle. The first cases of CPT II deficiency causing myopathy were reported in 1973. In 1983, Werneck et al published the first two Brazilian patients with myopathy due to CPT II deficiency, where the biochemical analysis confirmed deficient CPT activity in the muscle of both cases. Over the past 40 years since the pioneering publication, clinical phenotypes and genetic loci in the CPT2 gene have been described, and pathogenic mechanisms have been better elucidated. Genetic analysis of one of the original cases disclosed compound heterozygous pathogenic variants (p.Ser113Leu/p.Pro50His) in the CPT2 gene. Our report highlights the historical aspects of the first Brazilian publication of the myopathic form of CPT II deficiency and updates the genetic background of this pioneering publication.
Resumo Deficiência de carnitina palmitoiltransferase II (CPT II) é uma desordem de herança autossômica recessiva relacionada com o metabolismo do lipídio afetando músculo esquelético. Os primeiros dois casos de deficiência de CPT II causando miopatia foram relatados em 1973. Em 1983, Werneck et al. publicaram os primeiros pacientes brasileiros com miopatia por deficiência de CPT II, nos quais a análise bioquímica confirmou a atividade deficiente da CPT nos músculos em ambos os casos. Após 40 anos desde a publicação pioneira, fenótipos clínicos e loci genético no gene CPT2 foram descritos, bem com os mecanismos patológicos foram melhor elucidados. A análise genética de um dos casos da publicação original apresentou variantes patogênicas em heterozigose composta (p.Ser113Leu/p.Pro50His) no gene CPT2. O nosso relato destaca os aspectos históricos da primeira publicação brasileira da forma miopática da deficiência de CPT II e atualiza as bases genéticas dessa publicação pioneira.
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Durante el ayuno, la oxidación de ácidos grasos y la formación de cuerpos cetónicos son necesarios para la producción de energía. La carnitina es esencial para que los ácidos grasos de cadena larga se transfieran a la mitocondria para la oxidación de ácidos grasos. La deficiencia primaria de carnitina es un defecto recesivo que se expresa con un espectro clínico amplio que incluye descompensación metabólica, hipoglicemia hipocetósica o cardiomiopatía en la niñez, fatigabilidad en la adultez o ausencia de síntomas. En nuestro país no hay publicaciones sobre el tema, por lo que en el presente artículo se reporta el caso de un niño que presentó una deficiencia de carnitina expresada como hipoglicemia hipocetósica y se analiza sus hallazgos clínicos, bioquímicos e histopatológicos.
During fasting, the oxidation of fatty acids and the formation of ketone bodies are necessary for energy production. Carnitine is essential for long-chain fatty acids to be transferred to the mitochondria for fatty acid oxidation. Primary carnitine deficiency is a recessive defect that is expressed with a broad clinical spectrum that includes metabolic decompensation, hypoketotic hypoglycemia or cardiomyopathy in childhood, fatiguability in adulthood or absence of symptoms. In our country there are no publications on the subject, so this article reports the case of a child who had carnitine deficiency expressed as hypoketotic hypoglycemia and its clinical, biochemical and histopathological findings are analyzed.
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BACKGROUND: Epilepsy is a prevalent neurological disease, affecting approximately 1-2% of the global population. The hallmark of epilepsy is the occurrence of epileptic seizures, which are characterized by predictable behavioral changes reflecting the underlying neural mechanisms of the disease. Unfortunately, around 30% of patients do not respond to current pharmacological treatments. Consequently, exploring alternative therapeutic options for managing this condition is crucial. Two potential candidates for attenuating seizures are N-acetylcysteine (NAC) and Acetyl-L-carnitine (ALC), as they have shown promising neuroprotective effects through the modulation of glutamatergic neurotransmission. METHODS: This study aimed to assess the effects of varying concentrations (0.1, 1.0, and 10 mg/L) of NAC and ALC on acute PTZ-induced seizures in zebrafish in both adult and larval stages. The evaluation of behavioral parameters such as seizure intensity and latency to the crisis can provide insights into the efficacy of these substances. RESULTS: Our results indicate that both drugs at any of the tested concentrations were not able to reduce PTZ-induced epileptic seizures. On the other hand, the administration of diazepam demonstrated a notable reduction in seizure intensity and increased latencies to higher scores of epileptic seizures. CONCLUSION: Consequently, we conclude that, under the conditions employed in this study, NAC and ALC do not exhibit any significant effects on acute seizures in zebrafish.
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Epilepsia , Peixe-Zebra , Animais , Humanos , Adulto , Acetilcisteína/uso terapêutico , Acetilcarnitina/efeitos adversos , Larva , Pentilenotetrazol/toxicidade , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Epilepsia/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Modelos Animais de DoençasRESUMO
OBJECTIVE: To assess whether follicular fluid (FF) from infertile women with endometriosis in advanced stages [moderate/severe (EIII/IV) without or with endometrioma (Endometrioma)] induce more oocyte damages than in early stages (minimal/mild: EI/II); and whether supplementation with L-carnitine (LC) and omega 3 (n3) can prevent these oocyte damages. METHODS: Experimental study using bovine oocytes (obtained of ovaries from slaughterhouse), and human FF (samples were obtained during oocyte recovery for ICSI). Bovine oocytes were submitted to in vitro maturation (IVM) divided into 9 groups: no FF(No-FF), with 1% FF from infertile women without endometriosis (FFC), with EI/II, EIII/IV and Endometrioma, and with (or not) LC+n3 addition. After IVM, oocytes were fluorescently labelled and visualized by confocal microscopy to analyze chromosomes and spindle. RESULTS: FF from endometriosis decreased rate of normal MII (spindle assembly and chromosome alignment) compared to No-FF (87.2%) and FFC (87.2%). FFEIII/IV (80.7%) and FFEndometrioma (69.3%) decreased total MII rate compared to No-FF (91.9%) and FFC (89.2%), and FFEndometrioma had lower total MII rate compared to other groups. LC+n3 increased MII rate in the FFEIII/IV (80.7% vs. 90.8%) and the Endometrioma (69.3% vs. 86.4%), and it prevented damages in spindle and chromosomes in MII oocytes in the FFEI/II group (62.2% vs. 84.5%) and the FFEIII/IV group (70.2% vs. 84.1%). CONCLUSIONS: FF of endometriosis damaged the meiotic spindle of bovine MII oocytes. EIII/IV led to impaired nuclear maturation; FF from women with endometrioma had further negative impact in oocyte maturation. LC+n3 completely prevented the effects of FF from women with endometriosis on oocyte.
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Introduction: L-carnitine (LC) has been associated with inflammatory mediator reduction and with downregulating the angiotensin-converting enzyme-2 (ACE2) receptor, which is the target of SARS-CoV-2 attachment. Methods: This pilot phase 2 randomized, double-blind placebo-controlled trial contained two cohorts. Cohort 1 comprised 101 individuals with negative RT-PCR SARS-CoV-2 test results who cohabitated with an individual diagnosed with SARS-CoV-2 infection. Cohort 2 comprised 122 individuals with positive SARS-CoV-2 RT-PCR test results who were asymptomatic or had mild COVID-19 pneumonia symptoms. Participants in each cohort were randomized 1:1 to receive either 2 g elemental oral LC supplementation or placebo daily for 21 days. Primary endpoints included adverse events, SARS-CoV-2 infection incidence in Cohort 1, and disease progressions in Cohort 2. Secondary endpoints included between-group laboratory profile comparisons and Cohort 2 ACE1/ACE2 plasma levels. Disease progression was compared between the Cohort 2 groups using chest computed tomography. Results: In Cohort 1, two SARS-CoV-2 infections occurred in each group. The common adverse events included headache, dyspnea, and tiredness. In Cohort 2, platelet counts were elevated, and fibrinogen levels reduced in the LC group compared with those of the placebo group. Conclusion: Our study showed that LC was well-tolerated and suggests it modulates coagulation pathways. Furthermore, chest computed tomography images of the Cohort 2 LC group showed significant lung lesion improvement, suggesting that LC may slow COVID-19 progression.