L-Carnitine Attenuates Cardiac Dysfunction by Ischemic Insults Through Akt Signaling Pathway

Yin, Yin; Bi,; Li, Qing; Zhu, Wanxue; Guo, Youguang; Hu$^{, }$; Chen, Guihai; Rousselle,; Zhuang,; Liu, Ming; Cates,; Xue, Xiao

doi:10.1093/toxsci/kfx211

Cited by 6 publications

(6 citation statements)

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“…Romestaing et al [32] have demonstrated the increase in COX expression mediated by MCDD that alters mitochondrial metabolism, as demonstrated with elevated ROS level. In addition, other studies have described the capacity of LC to attenuate ROS accumulation and cardiac dysfunctions in ischemic or irradiated hearts [44,45] and to decrease oxidative stress in normal and hyperglycemic cardiomyocytes [46,21]. The present study confirmed that LC attenuates ROS production in the liver (Fig.…”

Section: Discussionsupporting

confidence: 88%

L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet

Mollica

Senesi

Codella

et al. 2020

Digestive and Liver Disease

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Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disorder. NAFLD, associated lipotoxicity, fibrosis, oxidative stress, and altered mitochondrial metabolism, is responsible for systemic inflammation, which contributes to organ dysfunction in extrahepatic tissues, including the heart. We investigated the ability of L-carnitine (LC) to oppose the pathogenic mechanisms underlying NAFLD progression and associated heart dysfunction, in a mouse model of methionine-choline-deficient diet (MCDD). Mice were divided into three groups: namely, the control group (CONTR) fed with a regular diet and two groups fed with MCDD for 6 weeks. In the last 3 weeks, one of the MCDD groups received LC (200 mg/kg each day) through drinking water (MCDD + LC). The hepatic lipid accumulation and oxidative stress decreased after LC supplementation, which also reduced hepatic fibrosis via modulation of ␣-smooth muscle actin (␣SMA), peroxisome-activated receptor gamma (PPAR␥), and nuclear factor kappa B (Nf B) expression. LC ameliorated systemic inflammation, mitigated cardiac reactive oxygen species (ROS) production, and prevented fibrosis progression by acting on signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase 1-2 (ERK1-2), and ␣SMA. This study confirms the existence of a relationship between fatty liver disease and cardiac abnormalities and highlights the role of LC in controlling liver oxidative stress, steatosis, fibrosis, and NAFLD-associated cardiac dysfunction.

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Section: Discussionsupporting

confidence: 88%

L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet

Mollica

Senesi

Codella

et al. 2020

Digestive and Liver Disease

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“…Therefore, LC may possess antioxidant properties beyond its action on lipid metabolism. There is overwhelming evidence that LC confers benefits in diabetic podocyte injury [5] and myocardial infarction [6]. We have demonstrated that LC treatment ameliorates cyclosporine-induced pancreatic and renal injury [7].…”

Section: S181mentioning

confidence: 77%

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction

Zhao

Jin

et al. 2021

Korean J Intern Med

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Background/Aims: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Methods: Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H 2 O 2 -exposed human kidney cells (HK-2) were treated with LC. Results: LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H 2 O 2 -exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. Conclusions: LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

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“…Disruptions in the Akt-regulated pathways have been demonstrated to be associated with cancer, diabetes, cardiovascular and neurological diseases (53-55). Therefore, miR-16-2-3p has potential to be used in multiple therapeutic areas as an Akt inhibitor.…”

Section: Discussionmentioning

confidence: 99%

miR‑16‑2‑3p inhibits cell proliferation and migration and induces apoptosis by targeting PDPK1 in�maxillary primordium mesenchymal cells

Han

Wang

et al. 2019

Int J Mol Med

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MicroRNAs (miRNAs) post-transcriptionally regulate gene expression by targeting the 3' untranslated region (UTR) of target genes, and serve diverse roles in cell proliferation, differentiation and apoptosis. However, the association between miR-16-2-3p and 3-phosphoinositide-dependent protein kinase-1 (PdPK1) in nonsyndromic cleft lip (NScL) remains unclear. In the present study, a luciferase activity assay indicated that miR-16-2-3p negatively regulated PdPK1 in maxillary primordium mesenchymal cells (MPMcs). In addition, it was confirmed that the expression levels of miR-16-2-3p was markedly increased in cleft lip tissues compared with those in adjacent normal lip tissues. A negative correlation between miR-16-2-3p and PdPK1 in cleft lip tissues was observed. Furthermore, miR-16-2-3p inhibited cell proliferation and migration, and induced apoptosis of MPMcs via repressing PdPK1. Finally, miR-16-2-3p exerted its suppressive role in MPMcs by inhibiting the PdPK1/protein kinase B signaling pathway. These results indicate that miR-16-2-3p may inhibit cell proliferation and migration, and promote apoptosis in MPMcs through repression of PdPK1 and may be a potential target for future clinical prevention and treatment of NScL.

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L-Carnitine Attenuates Cardiac Dysfunction by Ischemic Insults Through Akt Signaling Pathway

Cited by 6 publications

References 0 publications

L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet

L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction

miR‑16‑2‑3p inhibits cell proliferation and migration and induces apoptosis by targeting PDPK1 in�maxillary primordium mesenchymal cells

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