OBJECTIVE: A prominent, safe and efficient therapy for patients with chronic myeloid leukemia (CML) is inhibiting oncogenic protein BCR::ABL1 in a targeted manner with imatinib, a tyrosine kinase inhibitor. A substantial part of patients treated with imatinib report skeletomuscular adverse events affecting their quality of life. OCTN2 membrane transporter is involved in imatinib transportation into the cells. At the same time, the crucial physiological role of OCTN2 is cellular uptake of carnitine which is an essential co-factor for the mitochondrial β-oxidation pathway. This work investigates the impact of imatinib treatment on carnitine intake and energy metabolism of muscle cells. METHODS: HTB-153 (human rhabdomyosarcoma) cell line and KCL-22 (CML cell line) were used to study the impact of imatinib treatment on intracellular levels of carnitine and vice versa. The energy metabolism changes in cells treated by imatinib were quantified and compared to changes in cells exposed to highly specific OCTN2 inhibitor vinorelbine. Mouse models were used to test whether in vitro observations are also achieved in vivo in thigh muscle tissue. The analytes of interest were quantified using a Prominence HPLC system coupled with a tandem mass spectrometer. RESULTS: This work showed that through the carnitine-specific transporter OCTN2, imatinib and carnitine intake competed unequally and intracellular carnitine concentrations were significantly reduced. In contrast, carnitine preincubation did not influence imatinib cell intake or interfere with leukemia cell targeting. Blocking the intracellular supply of carnitine with imatinib significantly reduced the production of most Krebs cycle metabolites and ATP. However, subsequent carnitine supplementation rescued mitochondrial energy production. Due to specific inhibition of OCTN2 activity, the influx of carnitine was blocked and mitochondrial energy metabolism was impaired in muscle cells in vitro and in thigh muscle tissue in a mouse model. CONCLUSIONS: This preclinical experimental study revealed detrimental effect of imatinib on carnitine-mediated energy metabolism of muscle cells providing a possible molecular background of the frequently occurred side effects during imatinib therapy such as fatigue, muscle pain and cramps.
- MeSH
- chronická myeloidní leukemie * farmakoterapie metabolismus MeSH
- energetický metabolismus účinky léků MeSH
- imatinib mesylát * farmakologie škodlivé účinky MeSH
- inhibitory proteinkinas farmakologie škodlivé účinky MeSH
- karnitin * metabolismus farmakologie MeSH
- lidé MeSH
- mitochondrie metabolismus účinky léků MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- protinádorové látky škodlivé účinky farmakologie MeSH
- rodina nosičů rozpuštěných látek 22, člen 5 * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Acylcarnitines are important markers in metabolic studies of many diseases, including metabolic, cardiovascular, and neurological disorders. We reviewed analytical methods for analyzing acylcarnitines with respect to the available molecular structural information, the technical limitations of legacy methods, and the potential of new mass spectrometry-based techniques to provide new information on metabolite structure. We summarized the nomenclature of acylcarnitines based on historical common names and common abbreviations, and we propose the use of systematic abbreviations derived from the shorthand notation for lipid structures. The transition to systematic nomenclature will facilitate acylcarnitine annotation, reporting, and standardization in metabolomics. We have reviewed the metabolic origins of acylcarnitines important for the biological interpretation of human metabolomic profiles. We identified neglected isomers of acylcarnitines and summarized the metabolic pathways involved in the synthesis and degradation of acylcarnitines, including branched-chain lipids and amino acids. We reviewed the primary literature, mapped the metabolic transformations of acyl-CoAs to acylcarnitines, and created a freely available WikiPathway WP5423 to help researchers navigate the acylcarnitine field. The WikiPathway was curated, metabolites and metabolic reactions were annotated, and references were included. We also provide a table for conversion between common names and abbreviations and systematic abbreviations linked to the LIPID MAPS or Human Metabolome Database.
- MeSH
- karnitin * analogy a deriváty metabolismus biosyntéza MeSH
- lidé MeSH
- metabolické sítě a dráhy * MeSH
- metabolomika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The objective of this research was to determine the effect of L-carnitine antioxidant ability on some hematological parameters such as the extent of red blood corpuscles (RBCs), "Packed cells volume (PCV)", Hemoglobin (Hb), and Mean cellular volume (MCV) in normal and oxidative stress exposed rats respectively. Using an animal model, "Hydrogen peroxide ((H2O2 0.5 %)" was mixed with drinking tap water to induce oxidative stress through the experiment period (30 days). Three groups were used in this study (each containing 7 rats) one of them was the negative control group and the other two were the positive control group (oxidative stress group treated with H2O2) and the treatment group treated with H2O2 + L-carnitine. The oxidative stress group showed a significant decrease (P<0.05) in RBCs count, and no significant differences (P<0.05) were observed in Hb, PCV, and MCV compared with the control group on the other hand the treatment group revealed a significant increase (P<0.05) in RBCs count in cooperation with the oxidative stress group. It can be concluded that L-carnitine has a positive key role toward H2O2 induced oxidative stress. This role positively affects the red bone marrow and erythropoiesis through balancing the negative effect of oxidative stress and can be monitored through RBCs count only.
- MeSH
- erytrocyty MeSH
- erytropoéza fyziologie MeSH
- hematologické testy MeSH
- hemoglobiny MeSH
- karnitin * fyziologie krev terapeutické užití MeSH
- modely nemocí na zvířatech * MeSH
- oxidační stres fyziologie MeSH
- peroxid vodíku škodlivé účinky MeSH
- počet buněk MeSH
- výzkum MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD/MTPD) and medium chain acyl-CoA dehydrogenase deficiency (MCADD) were included in the expanded neonatal screening program (ENBS) in Czechia in 2009, allowing for the presymptomatic diagnosis and nutritional management of these patients. The aim of our study was to assess the nationwide impact of ENBS on clinical outcome. This retrospective study analysed acute events and chronic complications and their severity in pre-ENBS and post-ENBS cohorts. In total, 28 children (12 before, 16 after ENBS) were diagnosed with LCHADD/MTPD (incidence 0.8/100,000 before and 1.2/100,000 after ENBS). In the subgroup detected by ENBS, a significantly longer interval from birth to first acute encephalopathy was observed. In addition, improvement in neuropathy and cardiomyopathy (although statistically non-significant) was demonstrated in the post-ENBS subgroup. In the MCADD cohort, we included 69 patients (15 before, 54 after ENBS). The estimated incidence rose from 0.7/100,000 before to 4.3/100,000 after ENBS. We confirmed a significant decrease in the number of episodes of acute encephalopathy and lower proportion of intellectual disability after ENBS (p < 0.0001). The genotype-phenotype correlations suggest a new association between homozygosity for the c.1528C > G variant and more severe heart involvement in LCHADD patients.
- MeSH
- 3-hydroxyacyl-CoA-dehydrogenasy nedostatek MeSH
- acyl-CoA-dehydrogenasa nedostatek MeSH
- dítě MeSH
- hodnocení výsledků zdravotní péče MeSH
- incidence MeSH
- kardiomyopatie diagnóza dietoterapie epidemiologie MeSH
- karnitin analogy a deriváty krev MeSH
- kojenec MeSH
- lidé MeSH
- mitochondriální myopatie diagnóza dietoterapie epidemiologie MeSH
- mitochondriální trifunkční protein nedostatek MeSH
- nemoci nervového systému diagnóza dietoterapie epidemiologie MeSH
- novorozenec MeSH
- novorozenecký screening metody MeSH
- předškolní dítě MeSH
- retrospektivní studie MeSH
- rhabdomyolýza diagnóza dietoterapie epidemiologie MeSH
- stupeň závažnosti nemoci MeSH
- vrozené poruchy metabolismu tuků diagnóza dietoterapie epidemiologie MeSH
- vrozené poruchy metabolismu diagnóza MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Ve druhé části článek pojednává o zásadách výživy psů a koček s kardiovaskulárním onemocněním a zabývá se hlavními principy nutričního managementu. K významným dietním opatřením patří úprava klíčových minerálních látek, které ovlivňují činnost srdce i rozvoj kompenzačních změn provázejících srdeční selhání. A v neposlední řadě také dotace některých látek, které se mohou podílet na zmírnění patologických procesů a zlepšení funkce srdce. Jedná se především o n-3 mastné kyseliny, taurin a L-karnitin. Článek se zabývá také rizikovými faktory ve výživě, jež mohou přispět k rozvoji dilatační kardiomyopatie.
The second part of the article discusses the principles of nutrition for dogs and cats with cardiovascular disease and deals with the main principles of nutrient management. Important steps in diet include the alteration of key minerals that affect heart activity and the development of compensatory changes accompanying heart failure. And last but not least, supplementation of some sub-stances that may contribute to alleviating pathological processes and improving heart function. These are mainly n-3 fatty acids, taurine and L-carnitine. The article also deals with risk factors in nutrition that may contribute to the development of dilated cardiomyopathy.
- MeSH
- chloridy fyziologie MeSH
- dieta klasifikace veterinární MeSH
- dilatační kardiomyopatie dietoterapie etiologie veterinární MeSH
- fyziologie výživy zvířat MeSH
- kardiovaskulární nemoci * dietoterapie etiologie veterinární MeSH
- karnitin aplikace a dávkování fyziologie krev nedostatek MeSH
- kočky MeSH
- mastné kyseliny aplikace a dávkování chemie metabolismus MeSH
- proteiny MeSH
- psi MeSH
- sodík aplikace a dávkování fyziologie MeSH
- taurin aplikace a dávkování biosyntéza krev metabolismus nedostatek MeSH
- živiny * aplikace a dávkování fyziologie klasifikace krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- kočky MeSH
- psi MeSH
- zvířata MeSH
A feared adverse effect of dyslipidaemia therapy by fibrates is myopathy. We examined the effect of fenofibrate (FF) on protein and amino acid metabolism. Rats received a low (50 mg/kg, LFFD) or high (300 mg/kg, HFFD) dose of FF or vehicle daily by oral gavage. Blood plasma, liver, and soleus and extensor digitorum longus muscles were analysed after 10 days. The FF-treated rats developed hepatomegaly associated with increased hepatic carnitine and ATP and AMP concentrations, decreased protein breakdown, and decreased concentrations of DNA and triglycerides. HFFD increased plasma ALT and AST activities. The weight and protein content of muscles in the HFFD group were lower compared with controls. In muscles of the LFFD group there were increased ATP and decreased AMP concentrations; in the HFFD group AMP was increased. In both FF-treated groups there were increased glycine, phenylalanine, and citrulline and decreased arginine and branched-chain keto acids (BCKA) in blood plasma. After HFFD there were decreased levels of branched-chain amino acids (BCAA; valine, leucine and isoleucine), methionine, and lysine and increased homocysteine. Decreased arginine and increased glycine concentrations were found in both muscles in FF-treated animals; in HFFD-treated animals lysine, methionine, and BCAA were decreased. We conclude that FF exerts protein-anabolic effects on the liver and catabolic effects on muscles. HFFD causes signs of hepatotoxicity, impairs energy and protein balance in muscles, and decreases BCAA, methionine, and lysine. It is suggested that increased glycine and decreased lysine and methionine levels are due to activated carnitine synthesis; decreased BCAA and BCKA levels are due to increased BCAA oxidation.
- MeSH
- aminokyseliny účinky léků metabolismus MeSH
- energetický metabolismus účinky léků MeSH
- fenofibrát aplikace a dávkování MeSH
- glycin metabolismus MeSH
- hepatomegalie chemicky indukované metabolismus MeSH
- hypolipidemika aplikace a dávkování MeSH
- játra účinky léků metabolismus MeSH
- karnitin krev MeSH
- kosterní svaly účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- leucin metabolismus MeSH
- lidé MeSH
- lysin metabolismus MeSH
- methionin metabolismus MeSH
- oxidace-redukce MeSH
- potkani Wistar MeSH
- proteiny účinky léků metabolismus MeSH
- větvené aminokyseliny krev MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This study tested the hypothesis that in human aging, a decreased intramuscular acylcarnitine status is associated with (pre-)frailty, reduced physical performance, and altered mitochondrial function. We used a cross-sectional study design with well-matched fit and (pre-)frail old males and females, using young males and females as healthy controls. Frailty was assessed according to the Fried criteria and physical performance was determined by 400 m walk test, short physical performance battery and handgrip strength. Muscle and plasma acylcarnitine status, and muscle mitochondrial gene expression was analyzed. Results showed that intramuscular total carnitine levels and short-chain acylcarnitine levels were lower in (pre-)frail old females compared to fit old females and young females, whereas no differences were observed in males. The low intramuscular short-chain acylcarnitine levels in females correlated with low physical performance, even after correction for muscle mass (%), and were accompanied with lowered expression of genes involved in mitochondrial energy production and functionality. It is, therefore, concluded that in (pre-)frail old females, intramuscular total carnitine levels and short-chain acylcarnitine levels are decreased, and this decrease is associated with reduced physical performance and low expression of a wide range of genes critical for mitochondrial function. The results stress the importance of taking sex differences into account in aging research.
- MeSH
- chůze fyziologie MeSH
- karnitin analogy a deriváty krev chemie metabolismus MeSH
- křehkost metabolismus patofyziologie MeSH
- křehký senior MeSH
- lidé MeSH
- průřezové studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sexuální faktory MeSH
- síla ruky fyziologie MeSH
- stárnutí metabolismus fyziologie MeSH
- svaly metabolismus MeSH
- tělesná výkonnost fyziologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- antioxidancia terapeutické užití MeSH
- beta-karoten terapeutické užití MeSH
- fytoterapie metody MeSH
- Ginkgo biloba MeSH
- imunomodulace MeSH
- karnitin nedostatek terapeutické užití MeSH
- kyselina askorbová terapeutické užití MeSH
- léčivé rostliny MeSH
- lidé MeSH
- probiotika terapeutické užití MeSH
- roční období MeSH
- selen terapeutické užití MeSH
- syndromy imunologické nedostatečnosti prevence a kontrola terapie MeSH
- ubichinon terapeutické užití MeSH
- únava * imunologie prevence a kontrola terapie MeSH
- vitamin A terapeutické užití MeSH
- vitamin E terapeutické užití MeSH
- Check Tag
- lidé MeSH
Diabetická polyneuropatia je najčastejšou komplikáciou diabetu a súčasne najčastejšou príčinou syndrómu diabetickej nohy a bolesti pacientov s diabetes mellitus. V klinickej praxi ide stále o nedostatočne, resp. neskoro diagnostikované ochorenie, pričom práve terapeutický zásah v skorých štádiách ochorenia môže spomaliť (prípadne až zastaviť) progresiu polyneuropatie. Práca poskytuje súhrn aktuálnych možností prevencie a liečby diabetickej polyneuropatie a podáva prehľad o liekoch a nutraceutických produktoch, ktoré boli alebo sú v klinickom skúšaní.
Diabetic polyneuropathy is the most frequent complication of diabetes mellitus and at the same time the most common cause of diabetic foot syndrome and pain in patients with diabetes. This disorder is still being diagnosed insufficiently and too late in many cases. Therapeutic intervention in early stages could slow down (or completely stop) progression of the neuropathy. Presented paper reviews current possibilities of prevention and therapy of diabetic polyneuropathy as well as pharmaceuticals and nutraceuticals that were, or still are involved in clinical trials.
- MeSH
- acylkarnitin terapeutické užití MeSH
- amitriptylin aplikace a dávkování terapeutické užití MeSH
- diabetické neuropatie * terapie MeSH
- duloxetinum hydrochlorid aplikace a dávkování terapeutické užití MeSH
- gabapentin aplikace a dávkování terapeutické užití MeSH
- kyselina lipoová aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- neuralgie terapie MeSH
- polyneuropatie etiologie terapie MeSH
- pregabalin aplikace a dávkování terapeutické užití MeSH
- tapentadol aplikace a dávkování terapeutické užití MeSH
- thiamin aplikace a dávkování terapeutické užití MeSH
- tramadol aplikace a dávkování terapeutické užití MeSH
- vitamin B komplex terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
In Volume 8, Issue 2 of the International Journal of Celiac Disease, Shah et al. presented a peculiar celiac disease presenting as cardiomyopathy in an adult female. We would highlight the importance of carnitine deficiency in such cases, both at diagnosis as well as during follow up; carnitine being widely reported as a cause of cardiomyopathy in celiac and non-celiac population, and supplementing these patients by carnitine might reverse this heart dysfunction.
