Cytotoxicity and genotoxicity studies of two free-radical generators (AAPH and SIN-1) in human microvascular endothelial cells (HMEC-1) and human peripheral lymphocytes

Scarpato, Roberto; Gambacciani, Carolina; Svezia, B.; Chimenti, Daniele; Turchi, G.

doi:10.1016/j.mrgentox.2011.03.015

Cited by 12 publications

(5 citation statements)

References 62 publications

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“…In aqueous solutions, it is known that Azobis(2-amidinopropane) dihydrochloride (AAPH) decomposes to amidinopropyl radicals, which, in the presence of oxygen, are rapidly converted into hydroperoxyl radicals [ 27 , 28 ]. Therefore, we oxidized nLDL with AAPH in the presence of increasing amounts of EP in a separate set of experiments.…”

Section: Discussionmentioning

confidence: 99%

Ethyl pyruvate inhibits oxidation of LDL in vitro and attenuates oxLDL toxicity in EA.hy926 cells

et al. 2018

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BackgroundEthyl pyruvate (EP) exerts anti-inflammatory and anti-oxidative properties. The aim of our study was to investigate whether EP is capable of inhibiting the oxidation of LDL, a crucial step in atherogenesis. Additionally, we examined whether EP attenuates the cytotoxic effects of highly oxidized LDL in the human vascular endothelial cell line EA.hy926.MethodsNative LDL (nLDL) was oxidized using Cu2+ ions in the presence of increasing amounts of EP. The degree of LDL oxidation was quantified by measuring lipid hydroperoxide (LPO) and malondialdehyde (MDA) concentrations, relative electrophoretic mobilities (REMs), and oxidation-specific immune epitopes. The cytotoxicity of these oxLDLs on EA.hy926 cells was assessed by measuring cell viability and superoxide levels. Furthermore, the cytotoxicity of highly oxidized LDL on EA.hy926 cells under increasing concentrations of EP in the media was assessed including measurements of high energy phosphates (ATP).ResultsOxidation of nLDL using Cu2+ ions was remarkably inhibited by EP in a concentration-dependent manner, reflected by decreased levels of LPO, MDA, REM, oxidation-specific epitopes, and diminished cytotoxicity of the obtained oxLDLs in EA.hy926 cells. Furthermore, the cytotoxicity of highly oxidized LDL on EA.hy926 cells was remarkably attenuated by EP added to the media in a concentration-dependent manner reflected by a decrease in superoxide and an increase in viability and ATP levels.ConclusionsEP has the potential for an anti-atherosclerotic drug by attenuating both, the oxidation of LDL and the cytotoxic effect of (already formed) oxLDL in EA.hy926 cells. Chronic administration of EP might be beneficial to impede the development of atherosclerotic lesions.

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Section: Discussionmentioning

confidence: 99%

Ethyl pyruvate inhibits oxidation of LDL in vitro and attenuates oxLDL toxicity in EA.hy926 cells

et al. 2018

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“…A number of studies have employed AAPH to investigate antioxidant defenses in cellular systems [36,37]. More recently, cytotoxic and genotoxic effects of ROO • originating downstream of AAPH have been studied in a human microvascular endothelial cell line [38]. The effects of oxidative stress on the development of the cardiovascular system were also investigated after administration of AAPH in the air chamber of chicken embryos [39].…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress enhances and modulates protein S-nitrosation in smooth muscle cells exposed to S-nitrosoglutathione

Belcastro

Fries

et al. 2017

Nitric Oxide

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Among S-nitrosothiols showing reversible binding between NO and -SH group, S-nitrosoglutathione (GSNO) represents potential therapeutics to treat cardiovascular diseases (CVD) associated with reduced nitric oxide (NO) availability. It also induces S-nitrosation of proteins, responsible for the main endogenous storage form of NO. Although oxidative stress parallels CVD development, little is known on the ability of GSNO to restore NO supply and storage in vascular tissues under oxidative stress conditions. Aortic rat smooth muscle cells (SMC) were stressed in vitro with a free radical generator (2,2'-azobis(2-amidinopropane) dihydrochloride, AAPH). The cellular thiol redox status was reflected through levels of reduced glutathione and protein sulfhydryl (SH) groups. The ability of GSNO to deliver NO to SMC and to induce protein S-nitrosation (investigated via mass spectrometry, MS), as well as the implication of two redox enzymes involved in GSNO metabolism (activity of gamma-glutamyltransferase, GGT, and expression of protein disulfide isomerase, PDI) were evaluated. Oxidative stress decreased both intracellular glutathione and protein -SH groups (53% and 32% respectively) and caused a 3.5-fold decrease of GGT activity, while PDI expression at the plasma membrane was 1.7-fold increased without any effect on extracellular GSNO catabolism. Addition of GSNO (50 μM) increased protein -SH groups and protein S-nitrosation (50%). Mass spectrometry analysis revealed a higher number of S-nitrosated proteins under oxidative stress (83 proteins, vs 68 in basal conditions) including a higher number of cytoskeletal proteins (15, vs 9 in basal conditions) related with cell contraction, morphogenesis and movement. Furthermore, proteins belonging to additional protein classes (cell adhesion, transfer/carrier, and transporter proteins) were S-nitrosated under oxidative stress. In conclusion, higher levels of GSNO-dependent S-nitrosation of proteins from the cytoskeleton and the contractile machinery were identified under oxidative stress conditions. The findings may prompt the identification of suitable biomarkers for the appraisal of GSNO bioactivity in the CVD treatment.

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“…The accumulation of excess of reactive oxygen/nitrogen species in mammalian cell types is reported to develop oxidative/nitrosative damage, which could alter the cell functions and eventually lead to genetic material damage predominantly due to the oxidation of purines and pyrimidines. 51 These changes could play a key role in the development of several diseases including inflammation, atherosclerosis, and neurodegenerative ailments. Therefore, we studied the potential of BSA-MgNPs toward the prevention of DNA damage of mammalian cells induced due to lower catalase enzyme activity (Figure 5).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

BSA-Decorated Magnesium Nanoparticles for Scavenging Hydrogen Peroxide from Human Hepatic Cells

Shah

Pandya

Goyal

et al. 2020

ACS Appl. Nano Mater.

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Inorganic nanomaterials have gathered significant attention due to their biological enzyme-like catalytic activities, which are currently being utilized to display excellent biomedical applications. Among these, inorganic nanomaterials exhibiting catalase enzyme-like properties are of particular interest because they can impart protection to mammalian cells from cellular hydrogen peroxide (H2O2) and other free radicals. In this study, we have investigated the utility of bovine serum albumin (BSA) coated magnesium nanoparticles (BSA-MgNPs) with respect to the protection of mammalian hepatic cells with depleted cellular catalase enzyme. We observed that BSA-MgNPs lead to the rapid breakdown of H2O2 and therefore protect mammalian cells exposed to 3-amino-1,2,4-triazole (3-AT), an irreversible catalase enzyme inhibitor. Results revealed that 3-AT induces oxidative stress by challenging the glutathione (GSH) and catalase enzyme, thus altering the cellular redox balance, which leads to the formation of reactive oxygen species (ROS) in human hepatocytes (WRL-68). Results showed that BSA-MgNPs impart protection to the catalase depleted hepatic cells. Expression analysis showed that BSA-MgNPs favorably modulate cellular antioxidant proteins/enzymes and genes such as catalase, thioredoxin reductase (TrxR), peroxiredoxin 6 (Prx6), and Hsp 70 (heat shock protein). These results conclude that BSA-MgNPs impart protection to WRL-68 cells from acatalasia to display better cell survival as well as a remarkable decrease in the intracellular ROS levels.

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Cytotoxicity and genotoxicity studies of two free-radical generators (AAPH and SIN-1) in human microvascular endothelial cells (HMEC-1) and human peripheral lymphocytes

Cited by 12 publications

References 62 publications

Ethyl pyruvate inhibits oxidation of LDL in vitro and attenuates oxLDL toxicity in EA.hy926 cells

Ethyl pyruvate inhibits oxidation of LDL in vitro and attenuates oxLDL toxicity in EA.hy926 cells

Oxidative stress enhances and modulates protein S-nitrosation in smooth muscle cells exposed to S-nitrosoglutathione

BSA-Decorated Magnesium Nanoparticles for Scavenging Hydrogen Peroxide from Human Hepatic Cells

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