Carnitine depletion in rat pups from mothers given mildronate: A model of carnitine deficiency in late fetal and neonatal life

Peschechera, Alessandro; Scalibastri, Maurizio; Russo, Francesco; Giarrizzo, Mauro Giorgio; Carminati, Paolo; Giannessi, Fabio; Arduini, Arduino; Ricciolini, Rita

doi:10.1016/j.lfs.2005.03.029

Cited by 16 publications

(11 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…milk) of L-carnitine [9]. In our study, postnatal increases in serum free L-carnitine were consistent with levels reported in the literature [27] and these increases correlated with maturation of a number of enzymes and transporter systems that critically determine L-carnitine levels in the body.…”

Section: Discussionsupporting

confidence: 90%

See 1 more Smart Citation

Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

2012

View full text Add to dashboard Cite

BackgroundThe conditionally essential nutrient, L-carnitine, plays a critical role in a number of physiological processes vital to normal neonatal growth and development. We conducted a systematic evaluation of the developmental changes in key L-carnitine homeostasis mechanisms in the postnatal rat to better understand the interrelationship between these pathways and their correlation to ontogenic changes in L-carnitine levels during postnatal development.MethodsmRNA expression of heart, kidney and intestinal L-carnitine transporters, liver γ-butyrobetaine hydroxylase (Bbh) and trimethyllysine hydroxylase (Tmlh), and heart carnitine palmitoyltransferase (Cpt) were measured using quantitative RT-PCR. L-Carnitine levels were determined by HPLC-UV. Cpt and Bbh activity were measured by a spectrophotometric method and HPLC, respectively.ResultsSerum and heart L-carnitine levels increased with postnatal development. Increases in serum L-carnitine correlated significantly with postnatal increases in renal organic cation/carnitine transporter 2 (Octn2) expression, and was further matched by postnatal increases in intestinal Octn1 expression and hepatic γ-Bbh activity. Postnatal increases in heart L-carnitine levels were significantly correlated to postnatal increases in heart Octn2 expression. Although cardiac high energy phosphate substrate levels remained constant through postnatal development, creatine showed developmental increases with advancing neonatal age. mRNA levels of Cpt1b and Cpt2 significantly increased at postnatal day 20, which was not accompanied by a similar increase in activity.ConclusionsSeveral L-carnitine homeostasis pathways underwent significant ontogenesis during postnatal development in the rat. This information will facilitate future studies on factors affecting the developmental maturation of L-carnitine homeostasis mechanisms and how such factors might affect growth and development.

show abstract

Section: Discussionsupporting

confidence: 90%

“…Interestingly, L-carnitine levels in the milk of nursing rat dams decrease significantly by mid-lactation [30,31]. Despite the reduced exogenous L-carnitine, serum free L-carnitine levels in rat pups increase with advancing age [27]. The maturation of hepatic γ-Bbh contributes to the postnatal increase in L-carnitine levels in the body.…”

Section: Discussionmentioning

confidence: 99%

Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

2012

View full text Add to dashboard Cite

show abstract

“…In the current study, carnitine deficiency was induced in rats by daily intraperitoneal (i.p.) injection of DC (250 mg/kg/day) combined with MD (200 mg/kg/day) for 10 successive days according to previously published studies [17][18][19][20][21][22]. Depletion of L-carnitine by DC occurs via exchange of the D-and L-isomers across the cell membrane.…”

Section: Methodsmentioning

confidence: 99%

Progression of cyclophosphamide-induced acute renal metabolic damage in carnitine-depleted rat model

Sayed‐Ahmed

2010

Clin Exp Nephrol

View full text Add to dashboard Cite

show abstract

“…Nevertheless, in addition to increasing the expression of genes involved in mitochondrial β-oxidation, cooperation can also occur between mitochondria and peroxisomes as an adaptive mechanism to facilitate β-oxidation in mammals (57,58) . Some previous studies in mammals have shown that gene expression or enzyme activities associated with peroxisomal β-oxidation can be enhanced as an adaptation to the inhibition of mitochondrial β-oxidation (56,(59)(60)(61)(62) . In the present study, D-carnitine-treated tilapia exhibited higher expression of ACO, which encodes a key enzyme of peroxisomal β-oxidation, suggesting that peroxisomal β-oxidation may be up-regulated after D-carnitine treatment.…”

Section: Cooperation Between Mitochondria and Peroxisomesmentioning

confidence: 99%

Functional differences betweenl- andd-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model

Zhang

et al. 2019

Br J Nutr

View full text Add to dashboard Cite

Abstractl-Carnitine is essential for mitochondrial β-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals. d-Carnitine is an optical isomer of l-carnitine and dl-carnitine has been widely used in animal feeds. However, the functional differences between l- and d-carnitine are difficult to study because of the endogenous l-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences between l- and d-carnitine in nutrient metabolism in fish. l- or d-carnitine (0·4 g/kg diet) was fed to the low-carnitine tilapia for 6 weeks. l-Carnitine feeding increased the acyl-carnitine concentration from 3522 to 10 822 ng/g and alleviated the lipid deposition from 15·89 to 11·97 % in the liver of low-carnitine tilapia. However, as compared with l-carnitine group, d-carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11·97 to 20·21 % and the mRNA expression of the genes involved in β-oxidation and detoxification in the liver. d-Carnitine feeding also induced hepatic inflammation, oxidative stress and apoptosis. A metabolomic investigation further showed that d-carnitine feeding increased glycolysis, protein metabolism and activity of the tricarboxylic acid cycle and oxidative phosphorylation. Thus, l-carnitine can be physiologically utilised in fish, whereas d-carnitine is metabolised as a xenobiotic and induces lipotoxicity. d-Carnitine-fed fish demonstrates increases in peroxisomal β-oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore, d-carnitine is not recommended for use in farmed animals.

show abstract

Carnitine depletion in rat pups from mothers given mildronate: A model of carnitine deficiency in late fetal and neonatal life

Cited by 16 publications

References 50 publications

Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

Progression of cyclophosphamide-induced acute renal metabolic damage in carnitine-depleted rat model

Functional differences betweenl- andd-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model

Contact Info

Product

Resources

About