scholarly journals Iron release from haemosiderin and production of iron-catalysed hydroxyl radicals in vitro

1988 ◽  
Vol 250 (2) ◽  
pp. 589-595 ◽  
Author(s):  
M Ozaki ◽  
T Kawabata ◽  
M Awai
Keyword(s):  
Hydroxyl Radicals ◽  
Ph Dependence ◽  
Weight Ratio ◽  
Acidic Ph ◽  
Iron Release ◽  
Physiological Conditions ◽  
Radical Production ◽  
Acidic Conditions ◽  
Neutral Conditions

Isolated haemosiderin contained iron and nitrogen in a weight ratio of 6.75, with phosphorus and no detectable haem. Considerably more iron was released from haemosiderin under acidic conditions than under neutral conditions in the presence of ascorbate, nitrilotriacetate or dithionite. Unlike the situation with ascorbate, chelators such as citrate, ADP or succinate induced the release of only some iron, with almost no pH-dependence. Dehydroascorbate (the oxidized form of ascorbate with no reducing capacity) behaved like citrate, ADP, succinate or desferal, rather than like ascorbate itself, in releasing iron. GSH had less effect on the release of iron than these chelators, but in the presence of a small amount of chelator the release of iron increased, especially under acidic conditions. Thus reduction, chelation and pH were all found to be important factors involved in the release of iron from haemosiderin. Investigation by e.p.r. of hydroxyl-radical production by the released iron showed high radical productivity at an acidic pH. However, at a physiological pH, almost no radical formation was detected, except in the presence of nitrilotriacetate. These findings suggested that, under physiological conditions, haemosiderin was not an effective iron donor and was almost not involved in radical production. Under acidic conditions, however, such as in inflammation, hypoxia and in a lysosomal milieu, it could possibly be an iron donor and is thought to be implicated in radical production and tissue damage in iron-overloaded conditions.

scholarly journals Synthesis and In Vitro Assessment of pH-Sensitive Human Serum Albumin Conjugates of Pirarubicin

2020 ◽  
Vol 14 (1) ◽  
pp. 22
Author(s):  
Kenji Tsukigawa ◽  
Shuhei Imoto ◽  
Keishi Yamasaki ◽  
Koji Nishi ◽  
Toshihiko Tsutsumi ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Coupling Reaction ◽  
Synthetic Polymer ◽  
Ph Sensitive ◽  
Acidic Ph ◽  
Polymer Conjugate ◽  
Acidic Conditions

In a previous study, we reported on the development of a synthetic polymer conjugate of pirarubicin (THP) that was formed via an acid-labile hydrazone bond between the polymer and the THP. However, the synthetic polymer itself was non-biodegradable, which could lead to unexpected adverse effects. Human serum albumin (HSA), which has a high biocompatibility and good biodegradability, is also a potent carrier for delivering antitumor drugs. The objective of this study was to develop pH-sensitive HSA conjugates of THP (HSA-THP), and investigate the release of THP and the cytotoxicity under acidic conditions in vitro for further clinical development. HSA-THP was synthesized by conjugating maleimide hydrazone derivatives of THP with poly-thiolated HSA using 2-iminothiolane, via a thiol-maleimide coupling reaction. We synthesized two types of HSA-THP that contained different amounts of THP (HSA-THP2 and HSA-THP4). Free THP was released from both of the HSA conjugates more rapidly at an acidic pH, and the rates of release for HSA-THP2 and HSA-THP4 were similar. Moreover, both HSA-THPs exhibited a higher cytotoxicity at acidic pH than at neutral pH, which is consistent with the effective liberation of free THP under acidic conditions. These findings suggest that these types of HSA-THPs are promising candidates for further development.

Adsorption of zearalenone by Aspergillus japonicus conidia: new trends for biological decontamination in animal feed

2009 ◽  
Vol 2 (4) ◽  
pp. 391-397 ◽  
Author(s):  
G. Jard ◽  
T. Liboz ◽  
F. Mathieu ◽  
A. Guyonvarc'h ◽  
A. Lebrihi
Keyword(s):  
Heat Treatment ◽  
Animal Feed ◽  
Animal Health ◽  
Acidic Ph ◽  
Fusarium Spp ◽  
Aspergillus Japonicus ◽  
Heat Treated ◽  
Acidic Conditions ◽  
Influence Of Ph

Zearalenone (ZEA) is an oestrogenic mycotoxin produced by Fusarium spp. on a wide variety of grains. The presence of ZEA impairs farm animal health. In this study, the ability to remove ZEA by conidia of Aspergilli was evaluated in vitro. This mycotoxin was successfully eliminated in vitro by living and heat-treated conidia just after conidial inoculation, especially by Aspergillus japonicus Mu541 (IMI389204) conidia. Consequently, components involved in adsorption are not affected by heat-treatment. The influence of pH on ZEA removal was also determined. Results have shown that ZEA removal was 53% at pH 2 while 2% removal was observed at pH 11. Then, the adsorption capacity was evaluated in vitro in porcine gastrointestinal tract conditions. We observed that there was better adsorption in acidic stomach conditions. Finally, the phenomenon has been modelled using Hill's equation. This model was very suitable and confirmed better adsorption at acidic pH. Aspergilli section Nigri conidia were able to adsorb ZEA instantaneously especially in acidic conditions as in the stomach. The use of heat-treated conidia could be a very interesting means of decreasing ZEA levels in animal feed. It must now be assessed directly on naturally contaminated feed and on animals.

scholarly journals Dehydroflavonolignans from Silymarin Potentiate Transition Metal Toxicity In Vitro but Are Protective for Isolated Erythrocytes Ex Vivo

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 679
Author(s):  
Zuzana Lomozová ◽  
Václav Tvrdý ◽  
Marcel Hrubša ◽  
Maria Carmen Catapano ◽  
Kateřina Macáková ◽  
...  
Keyword(s):  
Fenton Reaction ◽  
Ex Vivo ◽  
Reducing Agent ◽  
Fenton Chemistry ◽  
Acidic Conditions ◽  
Copper Chelator ◽  
Neutral Conditions ◽  
Toxicity In Vitro

2,3-Dehydrosilybin (DHS) was previously shown to chelate and reduce both copper and iron ions. In this study, similar experiments with 2,3-dehydrosilychristin (DHSCH) showed that this congener of DHS also chelates and reduces both metals. Statistical analysis pointed to some differences between both compounds: in general, DHS appeared to be a more potent iron and copper chelator, and a copper reducing agent under acidic conditions, while DHSCH was a more potent copper reducing agent under neutral conditions. In the next step, both DHS and DHSCH were tested for metal-based Fenton chemistry in vitro using HPLC with coulometric detection. Neither of these compounds were able to block the iron-based Fenton reaction and, in addition, they mostly intensified hydroxyl radical production. In the copper-based Fenton reaction, the effect of DHSCH was again prooxidant or neutral, while the effect of DHS was profoundly condition-dependent. DHS was even able to attenuate the reaction under some conditions. Interestingly, both compounds were strongly protective against the copper-triggered lysis of red blood cells, with DHSCH being more potent. The results from this study indicated that, notwithstanding the prooxidative effects of both dehydroflavonolignans, their in vivo effect could be protective.

scholarly journals Potentiation of an antimalarial oxidant drug.

1997 ◽  
Vol 41 (7) ◽  
pp. 1449-1454 ◽  
Author(s):  
R W Winter ◽  
M Ignatushchenko ◽  
O A Ogundahunsi ◽  
K A Cornell ◽  
A M Oduola ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Hydroxyl Radicals ◽  
Fenton Reaction ◽  
Multidrug Resistant ◽  
Food Vacuole ◽  
Transformation Process ◽  
Prooxidant Activity ◽  
Acidic Conditions ◽  
Resistant Strains

In a previous report we described the synergistic antimalarial interaction between two structurally similar compounds, rufigallol and exifone. To explain this phenomenon, we proposed that exifone is transformed inside the parasitized erythrocyte into a xanthone with potent antimalarial properties. We speculated that the transformation process was induced by the prooxidant activity of rufigallol. On the basis of this model we hypothesized that exifone would act synergistically with other oxidant drugs. In the present study we have found a similar synergistic interaction between exifone and ascorbic acid (vitamin C) against both chloroquine-susceptible and multidrug-resistant strains of Plasmodium falciparum. The prooxidant activity of ascorbic acid against Plasmodium-infected erythrocytes is believed to result from an intraerythrocytic Fenton reaction occurring in the acidic food vacuole of the parasite. The hydroxyl radicals produced during this process are believed to attack exifone, which undergoes cyclodehydration to become 2,3,4,5,6-pentahydroxyxanthone (X5). Evidence presented to support this "xanthone hypothesis" includes the demonstration that the exifone ==> X5 transformation occurs readily in vitro under mildly acidic conditions in the presence of iron, ascorbic acid, and oxygen.

EFFECTS OF TANNINS ON SPORE GERMINATION AND GROWTH OF FUSARIUM SOLANI f. PHASEOLI AND VERTICILLIUM ALBO-ATRUM

1967 ◽  
Vol 13 (12) ◽  
pp. 1655-1661 ◽  
Author(s):  
J. A. Lewis ◽  
G. C. Papavizas
Keyword(s):  
Spore Germination ◽  
Fusarium Solani ◽  
Mycelial Growth ◽  
Complete Medium ◽  
Tannin Concentration ◽  
Alkaline Conditions ◽  
Acidic Conditions ◽  
Neutral Conditions ◽  
Verticillium Albo Atrum

Gallotannin, wattle, canaigre, and chestnut tannins in a complete medium affected in vitro spore germination and mycelial growth of Fusarium solani f. phaseoli and Verticillium albo-atrum. The pH values and tannin concentration were important factors determining the effectiveness of tannins as inhibitors. Under acidic conditions (pH 5), gallotannin, canaigre, and chestnut tannins at concentrations varying from 39 p.p.m. to 625 p.p.m. inhibited spore germination of both fungi. At a concentration of 1000 p.p.m. these tannins completely prevented growth at pH 5 of both fungi during a 20-day period. Under near neutral conditions (pH 6–7) there was a minimum inhibition of spore germination and mycelial growth with all tannins tested. Under alkaline conditions (pH 8) there was some degree of inhibition of spore germination, but, in general, growth was similar to that under neutral conditions. Wattle tannin was unusual in that it did not prevent growth of either fungus under acidic conditions although the growth of V. albo-atrum was appreciably reduced compared with the control. Gallotannin, however, prevented growth of both fungi under alkaline as well as acidic conditions.

Photocatalysis assisted by peroxymonosulfate and persulfate for benzotriazole degradation: effect of pH on sulfate and hydroxyl radicals

2015 ◽  
Vol 72 (11) ◽  
pp. 2095-2102 ◽  
Author(s):  
Mehdi Ahmadi ◽  
Farshid Ghanbari ◽  
Mahsa Moradi
Keyword(s):  
Water Resources ◽  
Hydroxyl Radicals ◽  
Catalyst Surface ◽  
Oxygen Demand ◽  
Emerging Pollutants ◽  
Acidic Ph ◽  
Total Organic Carbon Removal ◽  
Emerging Pollutant ◽  
Neutral Conditions ◽  
Degradation Effect

Recently, notable attempts have been devoted to removing emerging pollutants from water resources. Benzotriazole (BTA) as an emerging pollutant has widely been detected in the aquatic environment and water resources. In the current work, peroxymonosulfate (PMS) and persulfate (PS) were added to a TiO2/UV system for BTA degradation, as electron acceptors to overcome recombination of hole and electron. Additions of PMS and PS to the photocatalysis process considerably increased removal efficiency. The rate constants of UV/TiO2/PMS, UV/TiO2/PS and UV/TiO2 were 0.0217 min−1, 0.0152 min−1 and 0.0052 min−1 respectively. The results showed that pH significantly affected the UV/TiO2/PMS system while it marginally affected UV/TiO2/PS. Scavenging experiments using alcohols indicated that in acidic pH, the dominant oxidant was sulfate radical in both systems. The contribution of hydroxyl radical in BTA degradation was boosted at alkaline and neutral conditions especially in the UV/TiO2/PMS system. Moreover, other scavenging experiments implied that reaction of radicals occurred at both the catalyst surface and in solution. The mineralization results showed that PMS and PS significantly increased chemical oxygen demand and total organic carbon removal efficiencies. In general, presence of PMS in the photocatalysis process had a better performance compared to PS in terms of BTA removal and mineralization.

scholarly journals Synthesis and Antiproliferative Activity of Phosphorus Substituted 4-Cyanooxazolines, 2-Aminocyanooxazolines, 2-Iminocyanooxazolidines and 2-Aminocyanothiazolines by Rearrangement of Cyanoaziridines

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4265
Author(s):  
Victor Carramiñana ◽  
Ana M. Ochoa de Ochoa de Retana ◽  
Francisco Palacios ◽  
Jesús M. de los de los Santos
Keyword(s):  
Ring Opening ◽  
Human Lung ◽  
Ring Expansion ◽  
Moderate Activity ◽  
A549 Cell Line ◽  
One Pot ◽  
Acidic Conditions ◽  
Lung Adenocarcinoma A549 ◽  
High Yields

Several phosphorus-substituted N-acylated cyanoaziridines 2 and N-carbamoylated cyanoziridines 5 were prepared in good to high yields. N-Acylated cyanoaziridines 2 were used, after ring expansion, in an efficient synthesis of oxazoline derivative 3a and in a completely regio-controlled reaction in the presence of NaI. Conversely, N-carbamoyl cyanoaziridines 5 reacted with NaI to obtain a regioisomeric mixture of 2-aminocyanooxazolines 7. Mild acidic conditions can be used for the isomerization of N-thiocarbamoyl cyanoaziridine 6a into a 2-aminocyanothiazoline derivative 8a by using BF3·OEt2 as a Lewis acid. Likewise, a one pot reaction of NH-cyanoaziridines 1 with isocyanates obtained 2-iminocyanooxazolidines 9 regioselectively. This synthetic methodology involves the addition of isocyanates to starting cyanoaziridines to obtain N-carbamoyl cyanoaziridines 5, which after the ring opening, reacts with a second equivalent of isocyanate to give the final 2-imino cyanooxazolidines 9. In addition, the cytotoxic effect on the cell lines derived from human lung adenocarcinoma (A549) was also screened. 2-Iminooxazolidines 9 exhibited moderate activity against the A549 cell line in vitro. Furthermore, a selectivity towards cancer cells (A549) over non-malignant cells (MCR-5) was detected.

scholarly journals Doxorubicin loaded magnetism nanoparticles based on cyclodextrin dendritic-graphene oxide inhibited MCF-7 cell proliferation

2021 ◽  
Vol 12 (1) ◽  
pp. 8-15
Author(s):  
Ainaz Mihanfar ◽  
Niloufar Targhazeh ◽  
Shirin Sadighparvar ◽  
Saber Ghazizadeh Darband ◽  
Maryam Majidinia ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Anticancer Drug Delivery ◽  
Release Studies ◽  
Anti Cancer ◽  
Acidic Conditions ◽  
Mcf 7

Abstract Doxorubicin (DOX) is an effective chemotherapeutic agent used for the treatment of various types of cancer. However, its poor solubility, undesirable side effects, and short half-life have remained a challenge. We used a formulation based on graphene oxide as an anticancer drug delivery system for DOX in MCF-7 breast cancer cells, to address these issues. In vitro release studies confirmed that the synthesized formulation has an improved release profile in acidic conditions (similar to the tumor microenvironment). Further in vitro studies, including MTT, uptake, and apoptosis assays were performed. The toxic effects of the nanocarrier on the kidney, heart and liver of healthy rats were also evaluated. We observed that the DOX-loaded carrier improved the cytotoxic effect of DOX on the breast cell line compared to free DOX. In summary, our results introduce the DOX-loaded carrier as a potential platform for in vitro targeting of cancer cells and suggest further studies are necessary to investigate its in vivo anti-cancer potential.

scholarly journals Weakly Acidic Bile Is a Risk Factor for Hypopharyngeal Carcinogenesis Evidenced by DNA Damage, Antiapoptotic Function, and Premalignant Dysplastic Lesions In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 852 ◽  
Author(s):  
Clarence T. Sasaki ◽  
Sotirios G. Doukas ◽  
Panagiotis G. Doukas ◽  
Dimitra P. Vageli
Keyword(s):  
Premalignant Lesions ◽  
Acidic Ph ◽  
Upper Aerodigestive Tract ◽  
Carcinogenic Effect ◽  
Secondary Bile Acid ◽  
P53 Expression ◽  
Refractory Gerd ◽  
Antacid Therapy

Background: There is recent in vivo discovery documenting the carcinogenic effect of bile at strongly acidic pH 3.0 in hypopharynx, while in vitro data demonstrate that weakly acidic bile (pH 5.5) has a similar oncogenic effect. Because esophageal refluxate often occurs at pH > 4.0, here we aim to determine whether weakly acidic bile is also carcinogenic in vivo. Methods: Using 32 wild-type mice C57B16J, we performed topical application of conjugated primary bile acids with or without unconjugated secondary bile acid, deoxycholic acid (DCA), at pH 5.5 and controls, to hypopharyngeal mucosa (HM) twice per day, for 15 weeks. Results: Chronic exposure of HM to weakly acidic bile, promotes premalignant lesions with microinvasion, preceded by significant DNA/RNA oxidative damage, γH2AX (double strand breaks), NF-κB and p53 expression, overexpression of Bcl-2, and elevated Tnf and Il6 mRNAs, compared to controls. Weakly acidic bile, without DCA, upregulates the “oncomirs”, miR-21 and miR-155. The presence of DCA promotes Egfr, Wnt5a, and Rela overexpression, and a significant downregulation of “tumor suppressor” miR-451a. Conclusion: Weakly acidic pH increases the risk of bile-related hypopharyngeal neoplasia. The oncogenic properties of biliary esophageal reflux on the epithelium of the upper aerodigestive tract may not be fully modified when antacid therapy is applied. We believe that due to bile content, alternative therapeutic strategies using specific inhibitors of relevant molecular pathways or receptors may be considered in patients with refractory GERD.

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