The effect of an iron (III) chelator, silybin, on the proliferation and cell cycle of Jurkat cells: A comparison with desferrioxamine

Gharagozloo, Marjan; Khoshdel, Zahra; Amirghofran, Zahra

doi:10.1016/j.ejphar.2008.03.059

Cited by 61 publications

(47 citation statements)

References 32 publications

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“…4 Time dependent increases in cellular protein content (a) and cellular LDH activity (b) of OLN-93 cells after incubation without or with 100 or 1,000 lM FAC about 50 lM. This observation is consistent with literature data that demonstrate that DFX prevents cell proliferation of neuroblastoma cells [10], human B and T lymphocyte cell lines [5], T98 glioblastoma cells [4] and Jurkat cells [31], and demonstrates that also the proliferation of OLN-93 cells depends strongly on the availability of extracellular iron. The stability of the deferoxamine ferric iron complex is very high [32].…”

Section: Discussionsupporting

confidence: 92%

Effects of Iron Chelators, Iron Salts, and Iron Oxide Nanoparticles on the Proliferation and the Iron Content of Oligodendroglial OLN-93 Cells

2010

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The oligodendroglial cell line OLN-93 was used as model system to investigate the consequences of iron deprivation or iron excess on cell proliferation. Presence of ferric or ferrous iron chelators inhibited the proliferation of OLN-93 cells in a time and concentration dependent manner, while the application of a molar excess of ferric ammonium citrate (FAC) prevented the inhibition of proliferation by the chelator deferoxamine. Proliferation of OLN-93 cells was not affected by incubation with 300 microM iron that was applied in the form of FAC, FeCl(2), ferrous ammonium sulfate or iron oxide nanoparticles, although the cells efficiently accumulated iron during exposure to each of these iron sources. The highest specific iron content was observed for cells that were exposed to the nanoparticles. These data demonstrate that the proliferation of OLN-93 cells depends strongly on the availability of iron and that these cells efficiently accumulate iron from various extracellular iron sources.

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Section: Discussionsupporting

confidence: 92%

Effects of Iron Chelators, Iron Salts, and Iron Oxide Nanoparticles on the Proliferation and the Iron Content of Oligodendroglial OLN-93 Cells

2010

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“…In the present study, the formation of MetHb and the S-shaped curve obtained during kinetic behavior of Hb oxidation may provide an evidence for the formation of various free radicals during the process of hemoglobin oxidation, which seems compatible with previous findings reported by others (Lissi, 1998). Silibinin, the naturally occurring flavonolignan, acts mainly as an effective antioxidant (Wellington and Adis, 2001) and displays potential free radical scavenging property (Gharagozloo et al, 2008). Although the pharmacology of silibinin has been extensively studied, its molecular mechanisms of the antioxidative activity have not been systematically investigated and remain unclear (Gazak et al, 2009) and few studies have been devoted to the identification of silibinin active sites (Gyorgy et al, 1992).…”

Section: Discussionsupporting

confidence: 90%

Free radical scavenging activity of silibinin in nitrite-induced hemoglobin oxidation and membrane fragility models

Marouf

Zalzala

Al-Khalifa

et al. 2011

Saudi Pharmaceutical Journal

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Free radical formation in heme proteins is recognized as a factor in mediating the toxicity of many drugs. Xenobiotics and drug therapy-related toxicity, due to oxidative modification of hemoglobin (Hb), has been attributed in part to the uncontrolled oxidative reactions. A variety of antioxidant strategies to ameliorate potential oxidative damage in vivo have been suggested. The present study was designed to evaluate the dose-response relationship of the free radical scavenging properties of silibinin dihemisuccinate (SDH) in nitrite-induced Hb oxidation in vitro and in vivo. Different concentrations of SDH were added, before and after different intervals of inducing Hb oxidation in erythrocytes lysate, and formation of methemoglobin (MetHb) was monitored spectrophotometrically; the same approach was utilized to evaluate the effect of the same doses of SDH on the integrity of erythrocytes after induction of hemolysis. Moreover, the most effective dose of SDH was administered in rats before challenge with toxic dose of sodium nitrite, and MetHb formation was monitored as mentioned before. The results showed that in both in vitro and in vivo models, SDH successfully attenuates Hb oxidation after challenge with sodium nitrite; this protective effect was not related to the stage of the catalytic stage of Hb oxidation, though the effect was more prominent when the compound was administered before nitrite. In conclusion, SDH can effectively, in concentration-dependent pattern, attenuate sodium nitrite-induced Hb oxidation and maintain integrity of red blood cells both in vitro and in vivo.

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“…No reports on the electrochemistry of the Fe-silybin complex have yet appeared. However, one group has claimed a pro-oxidant effect from the combination of silybin and Fe on the JurkatE6-1 cell line, by the presumed generation of a redox-active complex [149]. The problem of the low aqueous solubility of silybin can be overcome by complexation with soy phosphatidylcholine, which has greater bioavailability [150,151].…”

Section: Silybin and Analogsmentioning

confidence: 98%

Synthetic and Natural Products as Iron Chelators

Sharpe

Richardson²,

Kalinowski³

et al. 2011

CTMC

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An evaluation of existing and proposed Fe chelators, both synthetic and natural products, for the treatment of Fe-overload disease must address a number of issues. There are fundamental parameters that determine the efficacy of a drug: absorption, distribution, metabolism, clearance and toxicity. However, the administration of chelator for Fe overload aims to generate Fe complexes in vivo that are able to be excreted. Hence, the chemical and pharmacological properties of the complexes formed are equally important as the chelators themselves. The redox properties of the Fe complexes formed is particularly relevant to their toxicity. If both Fe(II) and Fe(III) oxidation states of the complexes are biologically accessible, then there is potential for the auto-catalytic production of deleterious free radicals, by Fenton-type chemistry. In addition, since the burden of Fe overload disease falls predominantly on some of the poorest economies, the cost of a drug must be considered, as well as the mode of delivery. There are also possible issues with the use of naturally occurring ligands, which may form Fe complexes capable of being utilised by opportunistic bacteria. This review will concentrate on recent developments in our chemical understanding of existing chelators approved or proposed for use and will also consider some of the candidates from natural sources that have been recently proposed.

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The effect of an iron (III) chelator, silybin, on the proliferation and cell cycle of Jurkat cells: A comparison with desferrioxamine

Cited by 61 publications

References 32 publications

Effects of Iron Chelators, Iron Salts, and Iron Oxide Nanoparticles on the Proliferation and the Iron Content of Oligodendroglial OLN-93 Cells

Effects of Iron Chelators, Iron Salts, and Iron Oxide Nanoparticles on the Proliferation and the Iron Content of Oligodendroglial OLN-93 Cells

Free radical scavenging activity of silibinin in nitrite-induced hemoglobin oxidation and membrane fragility models

Synthetic and Natural Products as Iron Chelators

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