Lipid emulsion attenuates extrinsic apoptosis induced by amlodipine toxicity in rat cardiomyoblasts

Ok, Seong-Ho; Ahn, Seung Hyun; Kim, Hyun‐Jin; Lee, Soo Hee; Bae, Sung Il; Park, Kyeong-Eon; Hwang, Yeran; Shin, Il Woo; Yoon, Sangcheol; Sohn, Ju-Tae

doi:10.1177/0960327120964551

Cited by 7 publications

(22 citation statements)

References 30 publications

(63 reference statements)

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“…Furthermore, long chain fatty acids may activate myocyte calcium channels resulting in increased calcium influx 16 . The inhibition of amlodipine‐induced cardiomyoblast apoptosis using ILT has been demonstrated in a murine model 17 . Improvement of clinical signs is reported within 20 min of administration 30 ; however, response to therapy is unreliable 29 .…”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinemia/euglycemia and intravenous lipid emulsion therapy for the management of severe amlodipine toxicosis in a cat

Tinsman¹,

Bellis²

2021

Clinical Case Reports

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Section: Discussionmentioning

confidence: 99%

Hyperinsulinemia/euglycemia and intravenous lipid emulsion therapy for the management of severe amlodipine toxicosis in a cat

Tinsman¹,

Bellis²

2021

Clinical Case Reports

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“…DMT (10 −9 , 10 −8 , 10 −7 , and 10 −6 M) emulsified with LE (Intralipid: 1% and 3%) in Krebs solution was measured using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS: Water, Milford, MA, USA) [ 33 ]. To extract DMT from lipid emulsified samples, emulsified samples were centrifuged at 75,000× g for 40 min, and the aqueous layer containing DMT was injected into an Acquity UPLC BEH C18 column (100 × 2.1 mm, 1.7 μm; Waters) equilibrated with water/acetonitrile (99:1) (containing 0.1% formic acid).…”

Section: Methodsmentioning

confidence: 99%

Lipid Emulsion Enhances Vasoconstriction Induced by Dexmedetomidine in the Isolated Endothelium-Intact Aorta

Lee

Ahn

et al. 2021

IJMS

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This study aimed to examine the effect of lipid emulsion (LE) on the vasoconstriction induced by dexmedetomidine (DMT) in the isolated rat aorta and elucidate the associated cellular mechanism. The effect of LE, NW-nitro-L-arginine methyl ester (L-NAME), and methyl-β-cyclodextrin (MβCD) on the DMT-induced contraction was examined. We investigated the effect of LE on the DMT-induced cyclic guanosine monophosphate (cGMP) formation and DMT concentration. The effect of DMT, LE, 4-Amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo[3,4-d]pyrimidine,4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), and rauwolscine on the phosphorylation of endothelial nitric oxide synthase (eNOS), caveolin-1, and Src kinase was examined in the human umbilical vein endothelial cells. L-NAME, MβCD, and LE (1%, standardized mean difference (SMD): 2.517) increased the DMT-induced contraction in the endothelium-intact rat aorta. LE (1%) decreased the DMT (10−6 M) concentration (SMD: −6.795) and DMT-induced cGMP formation (SMD: −2.132). LE (1%) reversed the DMT-induced eNOS (Ser1177 and Thr496) phosphorylation. PP2 inhibited caveolin-1 and eNOS phosphorylation induced by DMT. DMT increased the Src kinase phosphorylation. Thus, LE (1%) enhanced the DMT-induced contraction by inhibition of NO synthesis, which may be caused by the decreased DMT concentration. DMT-induced NO synthesis may be caused by the increased eNOS (Ser1177) phosphorylation and decreased eNOS (Thr495) phosphorylation potentially mediated by Src kinase-induced caveolin-1 phosphorylation.

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“…The American Type Culture Collection supplied the H9c2 cardiomyoblasts (#CRL-1446, Rockville, MD, USA). H9c2 cells were maintained in high-glucose Dulbecco's modified Eagle's medium (DMEM) (#11995, Gibco, Life Technologies, Grand Island, NY, USA) with 10% fetal bovine serum (#16000, Gibco) and 1% penicillin/streptomycin (#15140122, Gibco) at 37°C in a 5% CO2 environment, as reported previously [22]. Prior to drug treatment, the cells were preincubated for 16 h in DMEM without serum.…”

Section: Cell Culturementioning

confidence: 99%

“…The Cell Counting Kit 8 (CCK-8) (#CK04-13, Dojindo Molecular Technologies, Kumamoto, Japan) was used to determine cell viability in accordance with the manufacturer's procedure, as reported previously [22]. Briefly, H9c2 cells were plated in 24-well dishes at 2 × 10 4 cells per well and treated for 24 h with various doses of chloroquine (10 -6 , 10 -5 , 10 -4 and 10 -3 M).…”

Section: Cell Viability Assaymentioning

confidence: 99%

“…Analysis of cleaved caspase-3, Bax, and cleaved caspase-8 protein levels in H9c2 cells was performed using western blotting, as reported previously [22]. For the evaluation of cleaved caspase-3 expression, cells were treated with chloroquine (10 -4 M) alone for 12 h; LE (Lipofundin MCT/LCT, 0.75%) or ROS scavenger (10 -4 M NAC or 10 -5 M mitotempo) for 1 h, followed by chloroquine (10 -4 M) for 12 h; and LE (0.75%) or ROS scavenger (10 -4 M NAC or 10 -5 M mitotempo) alone for 13 h. For the evaluation of Bax expression, cells were treated with chloroquine (10 -4 M) for 4 h; LE (0.75%) for 1 h, followed by chloroquine (10 -4 M) for 4 h; or LE (0.75%) alone for 5 h.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Lipid emulsion inhibits the cardiac toxicity caused by chloroquine via inhibition of reactive oxygen species production

Lee¹,

Ok²,

Ahn³

et al. 2023

Korean J Anesthesiol

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Background: Lipid emulsion (LE) is effective in treating intractable cardiac depression induced by the toxicity of highly lipid-soluble drugs including local anesthetics. However, the effect of LE on chloroquine-evoked cardiac toxicity remains unclear. This study aimed to examine the effect of Lipofundin MCT/LCT, an LE, on the cardiotoxicity caused by chloroquine in H9c2 rat cardiomyoblasts and elucidate the underlying cellular mechanism. Methods: The effects of chloroquine (1 × 10 -4 M), LE, and the reactive oxygen species (ROS) scavengers mitotempo and N-acetyl-L-cysteine (NAC), alone or combined, on cell viability and migration, apoptosis, ROS production, calcium levels, mitochondrial membrane potential, and adenosine triphosphate (ATP) were examined. Additionally, the effects of LE on the activities of catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) induced by chloroquine were assessed. Results: Pretreatment with LE, mitotempo, or NAC reversed the reduction in cell migration and viability, mitochondrial membrane potential, and ATP levels evoked by chloroquine, and inhibited the increase in cleaved caspase-3, ROS, and calcium concentration induced by chloroquine. LE inhibited the increase in Bax expression, TUNEL-positive cells, MDA activity, and late apoptosis, and reversed the reduction in SOD and CAT activity induced by chloroquine. Chloroquine did not significantly affect cleaved caspase-8 expression, and LE did not significantly affect chloroquine concentration.Conclusion: Collectively, these results suggest that LE with 50% long-chain and 50% mediumchain fatty acids inhibits the cardiotoxicity and late apoptosis induced by chloroquine toxicity via the intrinsic mitochondrial apoptotic pathway, which is associated with direct inhibition of ROS production.

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Lipid emulsion attenuates extrinsic apoptosis induced by amlodipine toxicity in rat cardiomyoblasts

Cited by 7 publications

References 30 publications

Hyperinsulinemia/euglycemia and intravenous lipid emulsion therapy for the management of severe amlodipine toxicosis in a cat

Hyperinsulinemia/euglycemia and intravenous lipid emulsion therapy for the management of severe amlodipine toxicosis in a cat

Lipid Emulsion Enhances Vasoconstriction Induced by Dexmedetomidine in the Isolated Endothelium-Intact Aorta

Lipid emulsion inhibits the cardiac toxicity caused by chloroquine via inhibition of reactive oxygen species production

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