How the Fatty Acyl Peroxyl Radical Determines the Outcome of Lipid Peroxidation

2021 ◽  
Author(s):  
Claus Schneider
Keyword(s):  
Lipid Peroxidation ◽  
Peroxyl Radical ◽  
Fatty Acyl

scholarly journals Drugs Repurposed as Antiferroptosis Agents Suppress Organ Damage, Including AKI, by Functioning as Lipid Peroxyl Radical Scavengers

2019 ◽  
Vol 31 (2) ◽  
pp. 280-296 ◽  
Author(s):  
Eikan Mishima ◽  
Emiko Sato ◽  
Junya Ito ◽  
Ken-ichi Yamada ◽  
Chitose Suzuki ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Cytochrome P450 ◽  
Liver Injury ◽  
Peroxyl Radical ◽  
Organ Damage ◽  
Peroxyl Radicals ◽  
Radical Scavengers ◽  
Lipid Peroxyl Radicals ◽  
Elevated Lipid

BackgroundFerroptosis, nonapoptotic cell death mediated by free radical reactions and driven by the oxidative degradation of lipids, is a therapeutic target because of its role in organ damage, including AKI. Ferroptosis-causing radicals that are targeted by ferroptosis suppressors have not been unequivocally identified. Because certain cytochrome P450 substrate drugs can prevent lipid peroxidation via obscure mechanisms, we evaluated their antiferroptotic potential and used them to identify ferroptosis-causing radicals.MethodsUsing a cell-based assay, we screened cytochrome P450 substrate compounds to identify drugs with antiferroptotic activity and investigated the underlying mechanism. To evaluate radical-scavenging activity, we used electron paramagnetic resonance–spin trapping methods and a fluorescence probe for lipid radicals, NBD-Pen, that we had developed. We then assessed the therapeutic potency of these drugs in mouse models of cisplatin-induced AKI and LPS/galactosamine-induced liver injury.ResultsWe identified various US Food and Drug Administration–approved drugs and hormones that have antiferroptotic properties, including rifampicin, promethazine, omeprazole, indole-3-carbinol, carvedilol, propranolol, estradiol, and thyroid hormones. The antiferroptotic drug effects were closely associated with the scavenging of lipid peroxyl radicals but not significantly related to interactions with other radicals. The elevated lipid peroxyl radical levels were associated with ferroptosis onset, and known ferroptosis suppressors, such as ferrostatin-1, also functioned as lipid peroxyl radical scavengers. The drugs exerted antiferroptotic activities in various cell types, including tubules, podocytes, and renal fibroblasts. Moreover, in mice, the drugs ameliorated AKI and liver injury, with suppression of tissue lipid peroxidation and decreased cell death.ConclusionsAlthough elevated lipid peroxyl radical levels can trigger ferroptosis onset, some drugs that scavenge lipid peroxyl radicals can help control ferroptosis-related disorders, including AKI.

Lipid Peroxidation in Membranes: The Peroxyl Radical Does Not “Float”

2014 ◽  
Vol 5 (10) ◽  
pp. 1653-1658 ◽  
Author(s):  
Julian Garrec ◽  
Antonio Monari ◽  
Xavier Assfeld ◽  
Lluis M. Mir ◽  
Mounir Tarek
Keyword(s):  
Lipid Peroxidation ◽  
Peroxyl Radical

scholarly journals Influence of malaria infection on peroxyl-radical trapping capacity in plasma from rural and urban Thai adults

1990 ◽  
Vol 64 (1) ◽  
pp. 257-271 ◽  
Author(s):  
D. I. Thurnham ◽  
Ratree Singkamani ◽  
R. Kaewichit ◽  
Kalaya Wongworapat
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin C ◽  
Malaria Infection ◽  
Peroxyl Radical ◽  
Nutritional Indices ◽  
Cholesterol Ratio ◽  
Radical Trapping ◽  
Rural And Urban ◽  
Duration Of Illness ◽  
Made In

Measurement of peroxyl-radical trapping capacity (TRAP) were made in plasma from patients with malaria from a rural and an urban Thai community. The results were compared with those from control subjects living in the same areas and chosen to match the patients closely. Measurements were also made of various antioxidants including nutritional indices vitamin C and α-tocopherol and the non-nutritional indices urate and protein-sulphydryl. Parasite counts, temperature on examination and the duration of illness were recorded together with measurements of plasma caeruloplasmin (EC1.16.3.1), retinol and malondialdehyde (MDA). In general, most measurements made in the villagers were lower than those in the comparable urban groups. The exceptions were caeruloplasmin and MDA when the latter was expressed as MDA: cholesterol ratio. TRAP values were extremely low in 50% of the villagers and 25% of the urban patients with malaria and these results correlated with retinol and vitamin C and inversely with malonaldehyde. The results suggested that low TRAP values are associated with lipid peroxidation and that vitamin C and possibly retinol may be destroyed by the oxidative conditions present in the plasma in this disease.

Plasma Platelet-Activating Factor–Acetyl Hydrolase Activity and the Levels of Free Forms of Biomarker of Lipid Peroxidation in Cerebrospinal Fluid of Patients With Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽  
2011 ◽  
Vol 70 (3) ◽  
pp. 602-609 ◽  
Author(s):  
Yutaka Hirashima ◽  
Masaru Doshi ◽  
Nakamasa Hayashi ◽  
Shunro Endo ◽  
Yoko Akazawa ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Acyl Chain ◽  
Platelet Activating Factor ◽  
Prostaglandin F2α ◽  
Fatty Acyl ◽  
Fatty Acyl Chain ◽  
Symptomatic Vasospasm

Abstract Background: Free radicals and lipid peroxidation are thought to be related to the vasospasm generation after subarachnoid hemorrhage (SAH). Plasma platelet-activating factor-acetyl hydrolase (PAF-AH) degrades phospholipids with an oxidatively modified fatty acyl chain. Objective: To compare plasma PAF-AH activity and free forms of biomarker of lipid peroxidation in cerebrospinal fluid (CSF) between patients with and without symptomatic vasospasm (SVS) after SAH. Methods: The identification of PAF-AH in CSF was performed by Western blotting. The genotype at position 279 of the plasma PAF-AH gene was determined. The activities of PAF-AH and the levels of free 8-iso-prostaglandin F2α (free isoPs), free hydroxyoctadecadienoic acid (free HODE), and free hydroxyeicosatetraenoic acid (free HETE) in CSF were measured. Results: The PAF-AH in CSF was confirmed to be only the plasma type. The genotype of the plasma PAF-AH was not different between patients with and without SVS. Free isoPs, free HODE, and free HETE showed higher values in patients without SVS in 0 to 4 days and 5 to 9 days after SAH. The PAF-AH activity also was higher in patients without SVS in 0 to 4 days and 5 to 9 days after SAH. The associations between PAF-AH activity and free isoPs, and between PAF-AH activity and free HODE were significant. Conclusion: Oxidized lipids of lipoproteins and blood cell membranes produced by reactive oxygen species in CSF when SAH occurs may be the main source of lipid peroxidation. Plasma PAF-AH can hydrolyze oxidized phospholipids, and may attenuate the spreading of lipid peroxidation and participate in defense mechanisms against vasospasm after SAH.

Benzylamine antioxidants: relationship between structure, peroxyl radical scavenging, lipid peroxidation inhibition and cytoprotection

1993 ◽  
Vol 36 (9) ◽  
pp. 1262-1271 ◽  
Author(s):  
Melvin J. Yu ◽  
Jefferson R. McCowan ◽  
Lee A. Phebus ◽  
Richard D. Towner ◽  
Peter P. K. Ho ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Peroxyl Radical ◽  
Radical Scavenging ◽  
Lipid Peroxidation Inhibition
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