Anti-apoptotic Effect of Acetyl-/-carnitine and l-Carnitine in Primary Cultured Neurons

Ishii, Taketoshi; Shimpo, Yasuko; Matsuoka, Yoshiki; Kawakami, Kiyoshi

doi:10.1016/s0021-5198(19)30606-7

Cited by 16 publications

(7 citation statements)

References 29 publications

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“…Additionally, ALC (10–50 μM or 1 mM) treatment protected against the addition of glutamic acid, kainic acid, and N -methyl- d -aspartic acid (NMDA) to the cell culture media in the same model, all of which caused cell death without supplementation of ALC . Similarly, a later study confirmed that LC (1–100 μM) and ALC (1–100 μM) protected against cell death when serum was removed for 3 days in a culture of embryonic day 18 rat cells from the cerebral cortex, thalamus, and striatum . Thus, those studies indicated that LC and ALC contributed to neuronal survival under stressful conditions.…”

Section: Preclinical Studies Of Lc/alc Treatment For Neurological Dis...mentioning

confidence: 78%

“…61 Similarly, a later study confirmed that LC (1−100 μM) and ALC (1−100 μM) protected against cell death when serum was removed for 3 days in a culture of embryonic day 18 rat cells from the cerebral cortex, thalamus, and striatum. 62 Thus, those studies indicated that LC and ALC contributed to neuronal survival under stressful conditions. Furthermore, in several models of aging, ALC (0.15−1.5 wt %/vol or 100 mg/kg/day via oral gavage [po] 1−3 mo) significantly improved mitochondrial function, reduced oxidized RNA, increased enzymatic activity and substrate binding, and restored carnitine levels of aged rodents to those of young rodents.…”

Section: Preclinical Studies Of Lc/alc Treatmentmentioning

confidence: 94%

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Neuroprotective Effects of Carnitine and Its Potential Application to Ameliorate Neurotoxicity

Latham

Wang

Patterson

et al. 2021

Chem. Res. Toxicol.

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Carnitine is an essential metabolite that is absorbed from the diet and synthesized in the kidney, liver, and brain. It ferries fatty acids across the mitochondrial membrane to undergo β-oxidation. Carnitine has been studied as a therapy or protective agent for many neurological diseases and neurotoxicity (e.g., prolonged anesthetic exposure-induced developmental neurotoxicity in preclinical models). Preclinical and clinical data support the notion that carnitine or acetyl carnitine may improve a patient’s quality of life through increased mitochondrial respiration, release of neurotransmitters, and global gene expression changes, showing the potential of carnitine beyond its approved use to treat primary and secondary carnitine deficiency. In this review, we summarize the beneficial effects of carnitine or acetyl carnitine on the central nervous system, highlighting protective effects against neurotoxicity-induced damage caused by various chemicals and encouraging a thorough evaluation of carnitine use as a therapy for patients suffering from neurotoxicant exposure.

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Section: Preclinical Studies Of Lc/alc Treatment For Neurological Dis...mentioning

confidence: 78%

Section: Preclinical Studies Of Lc/alc Treatmentmentioning

confidence: 94%

Neuroprotective Effects of Carnitine and Its Potential Application to Ameliorate Neurotoxicity

Latham

Wang

Patterson

et al. 2021

Chem. Res. Toxicol.

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“…Inducing antioxidant gene expression and shifts in both the mitochondrial and cytosolic redox states may be other probable mechanisms that, through them, ALC can exert antioxidant effects during oxidative stress [42]. Additionally, L-carnitine and ALC, through suppressing oxidative stress in mitochondria and then improving mitochondrial function, have shown antiapoptotic effects [43,44]. It has been reported that L-carnitine and its derivatives influence the expression of many genes that are implicated in the modulation of the production of free radicals, cellular antioxidant defenses, and restoration and stabilization of mitochondrial actions [45].…”

Section: Discussionmentioning

confidence: 99%

Clinical Evidence of Acetyl-L-Carnitine Efficacy in the Treatment of Acute Ischemic Stroke: A Pilot Clinical Trial

Mazdeh

Abolfathi

Sabetghadam

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. This study was undertaken to evaluate the influence of oral Acetyl-L-carnitine (ALC) in patients with acute ischemic stroke. Methods. Sixty-nine cases with acute ischemic stroke with the onset of symptoms less than 24 hours not candidates for reperfusion therapy were randomly assigned to either the ALC group (1000 mg three times per day for three consecutive days) or the matching placebo group. The study outcomes based on intention-to-treat criteria included the change in the modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) score from baseline to day 90, as well as the change in serum levels of the inflammatory and oxidative stress biomarkers over the 3-day treatment protocol. Results. The NIHSS score and mRS score on day 90 were improved by 5.82 and 0.94 scores, respectively, in the ALC-treated group compared to 2.83 and 0.11 scores, respectively, in the placebo-treated group, which demonstrated the superiority of ALC relative to placebo. By using the multivariable analysis after adjusting for other variables in the model, compared to the group treated with placebo, patients in the ALC group had lower NIHSS score ( β : -2.40, 95% CI: -0.69, -4.10 ( p = 0.007 )) and mRS score ( β : -1.18, 95% CI: -0.52, -1.84 ( p = 0.001 )) 90 days after the intervention. The percentage of patients with a favourable functional outcome at day 90, defined as mRS scores of 0 or 1, was significantly higher in the ALC group in comparison to the placebo group (52.9% versus 28.6%). Further, over the 3-day treatment protocol, in the patients receiving ALC, the serum levels of proinflammatory biomarkers, including soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and neuron-specific enolase (NSE), showed a significant decrease, while the serum levels of antioxidant biomarkers, including glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TAC), as well as the total L-carnitine’s level showed a significant increase compared to those in patients receiving placebo indicating significant alteration. Conclusions. Although preliminary, these results suggested that ALC administration during the acute phase of ischemic stroke might be helpful in improving functional and neurological outcomes that are probably linked to its anti-inflammatory and antioxidant properties. Trial Registration. This trial is registered with IRCT20150629022965N17 at Iranian Registry of Clinical Trials (registration date: 25/07/2018).

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“…In neuronal cells, L-carnitine has similar anti-apoptotic actions and thus has neuroprotective effect (Ishii, Shimpo, Matsuoka, & Kinoshita, 2000). In skeletal muscle cells, L-carnitine prevents F I G U R E 2 Scatter plots of Annexin V-FITC/PI staining in control or cells treated with various concentrations of L-carnitine (0, 1, 10 or 50 mM) in a quadrant analysis.…”

Section: Discussionmentioning

confidence: 99%

L‐carnitine increases cell proliferation and amino acid transporter expression via the activation of insulin‐like growth factor I signaling pathway in rat trophoblast cells

Zhang

Heng

et al. 2020

Food Science & Nutrition

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Early embryo implantation and development is primarily determined by the homeostasis between cellular apoptosis and proliferation as well as placental nutrient transporters. Recent studies showed that L‐carnitine enhances female reproductive performance. However, the potential function of L‐carnitine on placenta is largely unknown. In our study, primary rat trophoblast cells were separated and cultured for 12 hr in medium containing various concentrations of L‐carnitine (0, 1, 10, and 50 mM). Placenta trophoblast cells treated with 50 mM L‐carnitine increased the proportion of cells in S phase of the cell cycle ( p < .05). In addition, live cell percentage was increased when treated with either 10 mM or 50 mM L‐carnitine, which was accompanied with decreased necrotic cells, late apoptotic cells, and early apoptotic cells ( p < .05). Compared with the control treatment, the mRNA expression of insulin‐like growth factor I (IGF‐1) and insulin‐like growth factor I receptor (IGF‐1R) was higher in rat placenta trophoblasts treated with either 10 mM or 50 mM L‐carnitine ( p < .05). Similarly, sodium‐dependent neutral amino acid transporter (SNAT)‐1 and SNAT2 were up‐regulated in both mRNA and protein levels when trophoblast cells were treated with 50 mM L‐carnitine ( p < .05). Inhibiting downstream targets (Akt or ERK signaling pathways) of IGF‐1 signaling pathway partially blocked the effect the L‐carnitine‐induced increase in protein abundances of SNAT1 and SNAT2. Collectively, our data showed protective role of L‐carnitine on placenta trophoblast cells through the involvement of IGF‐1 signaling pathway.

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Anti-apoptotic Effect of Acetyl-/-carnitine and l-Carnitine in Primary Cultured Neurons

Cited by 16 publications

References 29 publications

Neuroprotective Effects of Carnitine and Its Potential Application to Ameliorate Neurotoxicity

Neuroprotective Effects of Carnitine and Its Potential Application to Ameliorate Neurotoxicity

Clinical Evidence of Acetyl-L-Carnitine Efficacy in the Treatment of Acute Ischemic Stroke: A Pilot Clinical Trial

L‐carnitine increases cell proliferation and amino acid transporter expression via the activation of insulin‐like growth factor I signaling pathway in rat trophoblast cells

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