Lipid peroxidation in hepatocyte cell cultures: Modulation by free radical scavengers and iron

Innes, G; Fuller, Barry; Hobbs, K. E. F.

doi:10.1007/bf02623889

Cited by 20 publications

(5 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). Furthermore, our results confirm those of Innes et al (1988), who reported that iron may be involved in the mechanism of lipid peroxidation, but this latter process is not related to cell lysis. Indeed, under our experimental conditions a significant amount of MDA was formed, but it was unrelated to cytolysis since it was also induced by iron salts alone (in the absence of GLOX), an experimental condition which did not induce any LDH leakage.…”

Section: Discussionsupporting

confidence: 94%

“…The following parameters (and their time courses) were measured to identify the effects of such a deliberate oxidative stress: lipid peroxidation using thiobarbituric acid reactive substances (TBARS) as an end product, release of lactate NAD + oxydoreductase (LDH) into the culture medium as a sign of cell lysis, and changes in intracellular glycogen and in protein synthesis rate as markers of metabolic function. Subsequent experiments were designed to hinder the tentative contribution of constitutive iron ions to the cytotoxic effect of H202 by adding desferrioxamine mesylate (Desferal), a strong and widely used iron chelator (Innes et al 1988;Schraufstatter et al 1988;Halliwell 1989;Jonas et al 1989;Kyle et al 1989). …”

Section: Introductionmentioning

confidence: 99%

“…Such a chemical process is a prerequisite for the initiation of lipid peroxidation (Morehouse et al 1983;Braughler et al 1986;Aust 1987, 1989), which could explain the toxicity of H202 as well as that of iron. Indeed cell injury due to iron overload has usually been associated with lipid peroxidation (Slivka et al 1986;Innes et al 1988;Morel et al 1990;Sharma et al 1990;Weinberg 1990), but, again, this atractive hypothesis is not universally accepted since cell injury in experimental iron overload has also been related to disturbances in liver mitochondrial calcium homeostasis (Masini et al 1989). Since iron and H202 may be closely associated in molecular mechanisms leading to cell toxicity (Halliwell andGutteridge 1984, 1986), it appeared worthwhile to coin-744 pare the effects of either H202 alone or H202 plus iron salts on both metabolic function and cellular viability.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cell death and lipid peroxidation in isolated hepatocytes incubated in the presence of hydrogen peroxide and iron salts

1992

View full text Add to dashboard Cite

The incubation of isolated hepatocytes in the presence of glucose plus glucose oxidase, a H2O2-generating system, resulted in extensive loss of cell viability, as expressed by the release of lactate dehydrogenase (LDH). Disturbance of metabolic functions such as glycogen and protein synthesis was also caused by H2O2, but in no case was malondialdehyde (MDA)-like products detected. The lytic effect of H2O2 was significantly enhanced by incubating hepatocytes in the presence of iron salts. Under these conditions, MDA-like products were detected, but lipid peroxidation and cell injury did not correlate. Iron chelators modulated the cytotoxicity of H2O2 in different (and opposite) ways: when iron was complexed with ADP, increased cell lysis was observed compared to uncomplexed iron plus H2O2. Iron-DTPA, on the contrary, decreased such a lytic effect. The preincubation of hepatocytes with desferrioxamine mesylate (Desferal; a strong iron chelator) abolished the cytolytic effects produced by the association of iron salts and H2O2, as well as the membrane oxidative injury due to H2O2 alone, thus suggesting the existence of an intracellular source of iron. This kind of mechanism (metal chelation rather than radical scavenging) is supported by the absence of any protective effect by some free radical scavengers against the oxidative injury induced by the association iron H2O2. Nevertheless, the glycogenolytic effects observed in the presence of H2O2 were not modified by Desferal. In our opinion, the cytotoxicity of the association H2O2 plus iron salts involves at least two different and independent mechanisms.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cell death and lipid peroxidation in isolated hepatocytes incubated in the presence of hydrogen peroxide and iron salts

1992

View full text Add to dashboard Cite

show abstract

“…Briefly, lipid peroxidation content was detected by incubation of supernatant of the untreated and treated spheres with an equal volume of 0.67% thiobarbituric acid in 95°C for 60 min ( Innes et al, 1988 ). Then, plates were centrifuged and the supernatants were measured at 532 nm.…”

Section: Methodsmentioning

confidence: 99%

Diethyldithiocarbamate-ferrous oxide nanoparticles inhibit human and mouse glioblastoma stemness: aldehyde dehydrogenase 1A1 suppression and ferroptosis induction

Abu-Serie,

Osuka,

Heikal

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

The development of effective therapy for eradicating glioblastoma stem cells remains a major challenge due to their aggressive growth, chemoresistance and radioresistance which are mainly conferred by aldehyde dehydrogenase (ALDH)1A1. The latter is the main stemness mediator via enhancing signaling pathways of Wnt/β-catenin, phosphatidylinositol 3-kinase/AKT, and hypoxia. Furthermore, ALDH1A1 mediates therapeutic resistance by inactivating drugs, stimulating the expression of drug efflux transporters, and detoxifying reactive radical species, thereby apoptosis arresting. Recent reports disclosed the potent and broad-spectrum anticancer activities of the unique nanocomplexes of diethyldithiocarbamate (DE, ALDH1A1 inhibitor) with ferrous oxide nanoparticles (FeO NPs) mainly conferred by inducing lipid peroxidation-dependent non-apoptotic pathways (iron accumulation-triggered ferroptosis), was reported. Accordingly, the anti-stemness activity of nanocomplexes (DE-FeO NPs) was investigated against human and mouse glioma stem cells (GSCs) and radioresistant GSCs (GSCs-RR). DE-FeO NPs exhibited the strongest growth inhibition effect on the treated human GSCs (MGG18 and JX39P), mouse GSCs (GS and PDGF-GSC) and their radioresistant cells (IC50 ≤ 70 and 161 μg/mL, respectively). DE-FeO NPs also revealed a higher inhibitory impact than standard chemotherapy (temozolomide, TMZ) on self-renewal, cancer repopulation, chemoresistance, and radioresistance potentials. Besides, DE-FeO NPs surpassed TMZ regarding the effect on relative expression of all studied stemness genes, as well as relative p-AKT/AKT ratio in the treated MGG18, GS and their radioresistant (MGG18-RR and GS-RR). This potent anti-stemness influence is primarily attributed to ALDH1A1 inhibition and ferroptosis induction, as confirmed by significant elevation of cellular reactive oxygen species and lipid peroxidation with significant depletion of glutathione and glutathione peroxidase 4. DE-FeO NPs recorded the optimal LogP value for crossing the blood brain barrier. This in vitro novel study declared the potency of DE-FeO NPs for collapsing GSCs and GSCs-RR with improving their sensitivity to chemotherapy and radiotherapy, indicating that DE-FeO NPs may be a promising remedy for GBM. Glioma animal models will be needed for in-depth studies on its safe effectiveness.

show abstract

“…Products of these reac tions include both peroxides and free radi cals, which themselves can react rapidly with a variety of biological compounds, including proteins, nucleic acids and lipids, usually resulting in their inactivation [4][5][6][7][8][9][10], From an experimental point of view, the problem then is one of determining whether any ob served effect of iron in vitro has physiologi cal significance. Even the distinction of 'pos itive' versus 'negative' effects is not always helpful, because what appear to be the former may be caused by the non-physiological inactivation of negative control ele ments.…”

Section: Introductionmentioning

confidence: 99%

Induction of Ferritin Synthesis in vitro: Problems of Specificity Inherent in the Use of Iron Compounds

Lin¹,

Walden

Thach³

1990

Enzyme

View full text Add to dashboard Cite

The potential importance of heme as a translational regulator has been recognized for nearly 30 years. However, the ability to distinguish the specific regulatory effects of heme from the nonspecific effects has been hampered by its high reactivity and its tendency to generate reactive by-products in most systems. In this article we discuss some of the technical difficulties in studying the effects of iron salts and compounds, notably heme, in biochemical systems in vitro. Data are presented which show that the nonspecific inhibitory effects of heme on two restriction endonucleases can be eliminated by (a) including a redox buffer in the reaction mixture, and (b) maintaining a sufficiently high total protein concentration. Under these conditions, the specific effects of hemin on the ferritin repressor protein are still observed. A possible relationship between these observations and the status of ‘free’ heme in vivo is considered.

show abstract

Lipid peroxidation in hepatocyte cell cultures: Modulation by free radical scavengers and iron

Cited by 20 publications

References 34 publications

Cell death and lipid peroxidation in isolated hepatocytes incubated in the presence of hydrogen peroxide and iron salts

Cell death and lipid peroxidation in isolated hepatocytes incubated in the presence of hydrogen peroxide and iron salts

Diethyldithiocarbamate-ferrous oxide nanoparticles inhibit human and mouse glioblastoma stemness: aldehyde dehydrogenase 1A1 suppression and ferroptosis induction

Induction of Ferritin Synthesis in vitro: Problems of Specificity Inherent in the Use of Iron Compounds

Contact Info

Product

Resources

About