Characteristics of Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

Aki, Tomoko; Egashira, Nobuaki; Hama, Mika; Yamauchi, Yui; Yano, Tomoaki; Itoh, Yoshinori; Oishi, Ryozo

doi:10.1254/jphs.fp0072035

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…We previously reported that GM induced cellular membrane injury immediately after treatment with GM, suggesting that GM induces necrotic cell death via injury of the cell membrane (5). In the present study, we found that Gly completely suppressed the GM-induced increase in PI uptake.…”

Section: Discussionsupporting

confidence: 74%

“…Taken together with these findings, our results suggest that several amino acids such as Gly protect against GM-induced endothelial cell injury. In addition, we previously reported that mannitol, a regulatory drug of osmotic pressure, had no effect on the GM-induced cell injury (5). Therefore, it is unlikely that osmotic pressure is involved in the protective effects of amino acids.…”

Section: Discussionmentioning

confidence: 95%

“…Boc-Phe-SerArg-AMC was dissolved in dimetyl sulfoxide. The concentrations (1.5 and 2 mM) of GM were chosen based on a previous report (5). The pH of amino acids was adjusted by diluted HCl or NaHCO 3 to neutral.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we reported that GM induces necrotic cell death via injury of the cell membrane in porcine aorta endothelial cells (PAECs) (5). Several amino acids protect against various cell injuries in cell lines including endothelial cells (6 -10).…”

Section: Introductionmentioning

confidence: 99%

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Protective Effects of Amino Acids Against Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

et al. 2008

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Abstract. Gabexate mesilate (GM), a serine protease inhibitor, often causes severe vascular injury. We previously reported that GM induced necrotic cell death via injury of the cell membrane in porcine aorta endothelial cells (PAECs). In the present study, we investigated the protective effects of amino acids against this GM-induced cell injury in PAECs.-threonine, and L-isoleucine significantly inhibited the GM-induced decrease of cell viability. Gly showed the most potent effect among these amino acids. Gly, L-Cys, L-Glu, and L-Gln also inhibited the GM-induced increase in the number of necrotic cells stained by propidium iodide (PI). However, these amino acids had no effect on the GM-induced inhibition of trypsin activity. Strychnine, MK-801, or dichlorokynurenic acid did not affect the protective effect of Gly. Gly completely suppressed the GM-induced increase in PI uptake, which occurred immediately after exposure to GM. These findings suggest that Gly exerts protection against GM-induced cellular membrane injury, and several amino acids such as Gly may be useful for prophylaxis of the GM-induced severe vascular injury.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protective Effects of Amino Acids Against Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

et al. 2008

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“…These observations were in agreement with the marked lag between the time of intravenous infusion and the subsequent appearance of vascular injury in patients receiving intravenous infusion of NIC. Wallin et al reported that the symptoms of vascular injuries tended to increase over 14 hr in patients receiving intravenous infusion of NIC (Aki et al, 2008). These findings suggest that monitoring the infusion site 12 hr after injection might contribute to early detection and rapid cure.…”

Section: Morphological Changes Of Nic-exposed Hmvecmentioning

confidence: 98%

Characterization of nicardipine hydrochloride-induced cell injury in human vascular endothelial cells

Ochi¹,

Kawai

Tanaka³

et al. 2015

J. Toxicol. Sci.

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-Nicardipine hydrochloride (NIC), a dihydropyridine calcium-channel blocking agent, has been widely used for the treatment of hypertension. Especially, nicardipine hydrochloride injection is used as first-line therapy for emergency treatment of abnormally high blood pressure. Although NIC has an attractive pharmacological profile, one of the dose-limiting factors of NIC is severe peripheral vascular injury after intravenous injection. The goal of this study was to better understand and thereby reduce NIC-mediated vascular injury. Here, we investigated the mechanism of NIC-induced vascular injury using human dermal microvascular endothelial cells (HMVECs). NIC decreased cell viability and increased percent of dead cells in a dose-dependent manner (10-30 μg/mL). Although cell membrane injury was not significant over 9 hr exposure, significant changes of cell morphology and increases in vacuoles in HMVECs were observed within 30 min of NIC exposure (30 μg/mL). Autophagosome labeling with monodansylcadaverine revealed increased autophagosomes in the NIC-treated cells, whereas caspase 3/7 activity was not increased in the NIC-treated cells (30 μg/mL). Additionally, NIC-induced reduction of cell viability was inhibited by 3-methyladenine, an inhibitor of autophagosome formation. These findings suggest that NIC causes severe peripheral venous irritation via induction of autophagic cell death and that inhibition of autophagy could contribute to the reduction of NIC-induced vascular injury.

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Effect of tributyltin on mammalian endothelial cell integrity

Botelho

Bernardini

Zannoni

et al. 2015

Comparative Biochemistry and Physiology Part C: Toxicology &

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Tributyltin (TBT), is a man-made pollutants, known to accumulate along the food chain, acting as an endocrine disruptor in marine organisms, with toxic and adverse effects in many tissues including vascular system. Based on the absence of specific studies of TBT effects on endothelial cells, we aimed to evaluate the toxicity of TBT on primary culture of porcine aortic endothelial cells (pAECs), pig being an excellent model to study human cardiovascular disease. pAECs were exposed for 24h to TBT (100, 250, 500, 750 and 1000nM) showing a dose dependent decrease in cell viability through both apoptosis and necrosis. Moreover the ability of TBT (100 and 500nM) to influence endothelial gene expression was investigated at 1, 7 and 15h of treatment. Gene expression of tight junction molecules, occludin (OCLN) and tight junction protein-1 (ZO-1) was reduced while monocyte adhesion and adhesion molecules ICAM-1 and VCAM-1 (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) levels increased significantly at 1h. IL-6 and estrogen receptors 1 and 2 (ESR-1 and ESR-2) mRNAs, after a transient decrease, reached the maximum levels after 15h of exposure. Finally, we demonstrated that TBT altered endothelial functionality greatly increasing monocyte adhesion. These findings indicate that TBT deeply alters endothelial profile, disrupting their structure and interfering with their ability to interact with molecules and other cells.

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Characteristics of Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

Cited by 8 publications

References 29 publications

Protective Effects of Amino Acids Against Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

Protective Effects of Amino Acids Against Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

Characterization of nicardipine hydrochloride-induced cell injury in human vascular endothelial cells

Effect of tributyltin on mammalian endothelial cell integrity

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