Lipid emulsion attenuates apoptosis induced by a toxic dose of bupivacaine in H9c2 rat cardiomyoblast cells

Abstract

<jats:p> The goal of this in vitro study was to investigate the effect of lipid emulsion on apoptosis induced by a toxic dose of bupivacaine (BPV) in H9c2 rat cardiomyoblast cell lines. The effect of lipid emulsion on the decreased cell viability and count induced by BPV or mepivacaine (MPV) in the H9c2 cells was assessed using an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay or a cell count assay. The effect of BPV or lipid emulsion combined with BPV on cleaved caspase 3, caspase 8, and Bax in H9c2 cells was investigated using Western blotting. A terminal deoxynucleotidyl transferase dUTP2′-deoxyuridine 5′-triphosphate nick end-labeling (TUNEL) assay was performed to detect apoptosis of H9c2 cells treated with BPV alone or lipid emulsion combined with BPV. The magnitude of lipid emulsion-mediated attenuation of decreased cell viability induced by BPV was higher than that of lipid emulsion-mediated attenuation of decreased cell viability induced by MPV. Lipid emulsion attenuated the increases in cleaved caspase 3, caspase 8 and Bax induced by BPV. Lipid emulsion attenuated the increases in TUNEL-positive cells induced by BPV. These results suggest that lipid emulsion attenuates a toxic dose of BPV-induced apoptosis via inhibition of the extrinsic and intrinsic apoptotic pathways. The protective effect of lipid emulsion may be partially associated with the relatively high lipid solubility of BPV. </jats:p>

Lipid emulsion inhibits vasodilation induced by a toxic dose of bupivacaine by suppressing bupivacaine-induced PKC and CPI-17 dephosphorylation but has no effect on vasodilation induced by a toxic dose of mepivacaine

“…Pre-treatment or post-treatment with lipid emulsion in in vitro studies performed using isolated vessels has been demonstrated to reverse or attenuate the vasodilation induced by toxic doses of local anesthetics in a lipid solubility-dependent manner [ 3 7 12 23 ]. In H9c2 cells, lipid emulsion-mediated inhibition of apoptosis induced by a toxic dose of bupivacaine is enhanced compared with that induced by a toxic dose of mepivacaine [ 24 ]. In addition, pre-treatment or post-treatment with lipid emulsion has been shown in in vivo studies to be effective during recovery from cardiac arrest induced by bupivacaine but to have no effect on recovery from cardiac arrest induced by mepivacaine, suggesting that the efficacy of lipid emulsion treatment is partly dependent on the lipid solubility of the local anesthetic [ 25 26 ].…”

“…In addition, pre-treatment or post-treatment with lipid emulsion has been shown in in vivo studies to be effective during recovery from cardiac arrest induced by bupivacaine but to have no effect on recovery from cardiac arrest induced by mepivacaine, suggesting that the efficacy of lipid emulsion treatment is partly dependent on the lipid solubility of the local anesthetic [ 25 26 ]. All of these previous studies indicate that lipid emulsion-mediated recovery from cardiovascular collapse due to local anesthetic toxicity can be partly attributed to lipid emulsion-mediated sequestration of the local anesthetics, which is dependent on their lipid solubility [ 1 3 7 12 23 24 25 26 ]. Similar to previous reports, in the current study, lipid emulsion attenuated vasodilation induced by a toxic dose of bupivacaine ( Fig.…”

“…1A ) but had no effect on that induced by mepivacaine ( Fig. 1B ), suggesting that lipid emulsion-mediated attenuation of vasodilation is dependent on the lipid solubility of the local anesthetic (h-octanol/buffer partition coefficient: bupivacaine [346] versus mepivacaine [21]) [ 3 7 12 23 24 25 26 27 ]. As lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation ( Fig.…”

The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs

“…Lipid emulsion may also protect myocardial cells form local anesthetic -induced apoptosis. 12 Another proposed mechanisms is a metabolic benefit of lipid emulsion that reverses local anesthetic-induced inhibition of mitochondrial respiration in cardiac tissue. 13 In isolated myocardial mitochondria, the main depressive effect of bupivacaine on the mitochondrial respiratory chain is the inhibition of complex I (nicotinamide adenine dinucleotide [NADH] dehydrogenase).…”

T-2 Toxin Induces Oxidative Stress, Apoptosis and Cytoprotective Autophagy in Chicken Hepatocytes

“…Apoptosis is a crucial physiological cell death process that can be induced by toxic stimuli [25]. Previous studies have shown that T-2 toxin injection can strongly induce cell apoptosis in different tissues, such as thymus, spleen and liver, particularly in the liver [6].…”