In vivo and in vitro Studies of Acute and Chronic Iron Toxicity in Liver: Evidence for Free Radical-Mediated Lipid Peroxidation

1985 ◽  
Vol 69 (s12) ◽  
pp. 64P-64P
Author(s):  
M.J. O'Connell ◽  
R.J. Ward ◽  
H. Baum ◽  
T.J. Peters
Keyword(s):  
Lipid Peroxidation ◽  
Free Radical ◽  
Iron Toxicity ◽  
In Vitro Studies

scholarly journals Iron toxicity, lipid peroxidation and ferroptosis after intracerebral haemorrhage

2019 ◽  
Vol 4 (2) ◽  
pp. 93-95 ◽  
Author(s):  
Jieru Wan ◽  
Honglei Ren ◽  
Jian Wang
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Intracerebral Haemorrhage ◽  
Neuronal Death ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Iron Toxicity ◽  
Secondary Brain Injury

Intracerebral haemorrhage (ICH) is a devastating type of stroke with high mortality and morbidity. However, we have few options for ICH therapy and limited knowledge about post-ICH neuronal death and related mechanisms. In the aftermath of ICH, iron overload within the perihaematomal region can induce lethal reactive oxygen species (ROS) production and lipid peroxidation, which contribute to secondary brain injury. Indeed, iron chelation therapy has shown efficacy in preclinical ICH studies. Recently, an iron-dependent form of non-apoptotic cell death known as ferroptosis was identified. It is characterised by an accumulation of iron-induced lipid ROS, which leads to intracellular oxidative stress. The ROS cause damage to nucleic acids, proteins and lipid membranes, and eventually cell death. Recently, we and others discovered that ferroptosis does occur after haemorrhagic stroke in vitro and in vivo and contributes to neuronal death. Inhibition of ferroptosis is beneficial in several in vivo and in vitro ICH conditions. This minireview summarises current research on iron toxicity, lipid peroxidation and ferroptosis in the pathomechanisms of ICH, the underlying molecular mechanisms of ferroptosis and the potential for combined therapeutic strategies. Understanding the role of ferroptosis after ICH will provide a vital foundation for cell death-based ICH treatment and prevention.

scholarly journals A REVIEW ON ANTIOXIDANT METHODS

2016 ◽  
pp. 14 ◽  
Author(s):  
Dontha Sunitha
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Peroxidation ◽  
Antioxidant Activity ◽  
Free Radical ◽  
Oxygen Species ◽  
Antioxidant Assay ◽  
Antioxidant Effects ◽  
In Vitro Antioxidant Activity

<p>ABSTRACT<br />To provide an outlook of the various available methods of antioxidant activity. Various available in vitro and in vivo methods are listed and the<br />procedure to perform the method, its mechanism is also explained in brief. 1,1-diphenyl-2-picrylhydrazyl method was found to be used mostly for the<br />in vitro antioxidant activity evaluation purpose while lipid peroxidation was found as mostly used in vivo antioxidant assay. An ethanol was with the<br />highest frequency as a solvent for extraction purpose. Summarized information on the various methods available provides with reliable information<br />to confirm the benefits of antioxidant effects.<br />Keywords: Antioxidant activity, Reactive oxygen species, Free radical, 1,1-diphenyl-2-picrylhydrazyl, Flavonoid.</p>

scholarly journals Epidermal Growth Factor Protects Neuronal Cells In Vivo and In Vitro against Transient Forebrain Ischemia- and Free Radical-Induced Injuries

1998 ◽  
Vol 18 (4) ◽  
pp. 349-360 ◽  
Author(s):  
Hui Peng ◽  
Tong-Chun Wen ◽  
Junya Tanaka ◽  
Nobuji Maeda ◽  
Seiji Matsuda ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Free Radical ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cultured Neurons ◽  
Forebrain Ischemia ◽  
Hippocampal Ca1 ◽  
Epidermal Growth

Epidermal growth factor (EGF) has been considered to be a candidate for neurotrophic factors on the basis of the results of several in vitro studies. However, the in vivo effect of EGF on ischemic neurons as well as its mechanism of action have not been fully understood. In the present in vivo study using a gerbil ischemia model, we examined the effects of EGF on ischemia-induced learning disability and hippocampal CA1 neuron damage. Cerebroventricular infusion of EGF (24 or 120 ng/d) for 7 days to gerbils starting 2 hours before or immediately after transient forebrain ischemia caused a significant prolongation of response latency time in a passive avoidance task in comparison with the response latency of vehicle-treated ischemic animals. Subsequent histologic examinations showed that EGF effectively prevented delayed neuronal death of CA1 neurons in the stratum pyramidale and preserved synapses intact within the strata moleculare, radiatum, and oriens of the hippocampal CA1 region. In situ detection of DNA fragmentation (TUNEL staining) revealed that ischemic animals infused with EGF contained fewer TUNEL-positive neurons in the hippocampal CA1 field than those infused with vehicle alone at the seventh day after ischemia. In primary hippocampal cultures, EGF (0.048 to 6.0 ng/mL) extended the survival of cultured neurons, facilitated neurite outgrowth, and prevented neuronal damage caused by the hydroxyl radical-producing agent FeSO4 and by the peroxynitrite-producing agent 3-morpholinosydnonimine in a dose-dependent manner. Moreover, EGF significantly attenuated FeSO4-induced lipid peroxidation of cultured neurons. These findings suggest that EGF has a neuroprotective effect on ischemic hippocampal neurons in vivo possibly through inhibition of free radical neurotoxicity and lipid peroxidation.

scholarly journals HIV gene expression deactivates redox-sensitive stress response program in mouse tubular cells both in vitro and in vivo

2012 ◽  
Vol 302 (1) ◽  
pp. F129-F140 ◽  
Author(s):  
Divya Salhan ◽  
Shresh Pathak ◽  
Mohammad Husain ◽  
Pranai Tandon ◽  
Dileep Kumar ◽  
...  
Keyword(s):  
Free Radical ◽  
Stress Response ◽  
Cell Apoptosis ◽  
In Vitro Studies ◽  
Tubular Cell ◽  
Ros Generation ◽  
Tubular Cells ◽  
Hiv 1

Human immunodeficiency virus (HIV)-1 has been reported to cause tubular cell injury both in in vivo and in vitro studies. In the present study, we evaluated the role of oxidative stress in the induction of apoptosis in HIV gene expressing mouse tubular cells in in vivo (Tg26, a transgenic mouse model of HIV-associated nephropathy) and in vitro (tubular cells were transduced with pNL4-3: ΔG/P-GFP, VSV.G psueudo typed virus) studies. Although Tg26 mice showed enhanced tubular cell reactive oxygen species (ROS) generation and apoptosis, renal tissue did not display a robust antioxidant response in the form of enhanced free radical scavenger (MnSOD/catalase) expression. Tg26 mice not only showed enhanced tubular cell expression of phospho-p66ShcA but also displayed nuclear Foxo3a translocation to the cytoplasm. These findings indicated deactivation of tubular cell Foxo3A-dependent redox-sensitive stress response program (RSSRP) in Tg26 mice. In in vitro studies, NL4-3 (pNL4-3: ΔG/P-GFP, VSV.G pseudotyped virus)-transduced mouse proximal tubular cells (NL4-3/MPTEC) displayed enhanced phosphorylation of p66ShcA. NL4-3/MPTECs also displayed greater ( P < 0.01) ROS generation when compared with empty vector-transduced tubular cells; however, both diminution of p66ShcA and N-acetyl cysteine attenuated NL4-3-induced tubular cell ROS generation as well as apoptosis. In addition, both antioxidants and free radical scavengers partially inhibited HIV-induced tubular cell apoptosis. NL4-3/MPTEC displayed deactivation of RSSRP in the form of enhanced phosphorylation of Foxo3A and attenuated expression of superoxide dismutase (SOD) and catalase. Since both SOD and catalase were able to provide protection against HIV-1-induced tubular cell apoptosis, it suggests that HIV-1-induced proapoptotic effect may be a consequence of the deactivated RSSRP.

Carbon tetrachloride toxicity as a model for studying free-radical mediated liver injury

1985 ◽  
Vol 311 (1152) ◽  
pp. 633-645 ◽  
Keyword(s):  
Lipid Peroxidation ◽  
Endoplasmic Reticulum ◽  
Cell Division ◽  
Free Radical ◽  
Tissue Injury ◽  
Biological Activities ◽  
Covalent Binding ◽  
Liver Tumours

A single dose of CC1 4 when administered to a rat produces centrilobular necrosis and fatty degeneration of the liver. These hepatotoxic effects of CC1 4 are dependent upon its metabolic activation in the liver endoplasmic reticulum to reactive intermediates, including the trichloromethyl free radical. Positive identification of the formation of this free radical in vivo, in isolated liver cells and in microsomal suspensions in vitro has been achieved by e.s.r. spin-trapping techniques. The trichloromethyl radical has been found to be relatively unreactive in comparison with the secondarily derived peroxy radical CCl 3 O 2 , although each free radical species contributes significantly to the biological disturbances that occur. Major early perturbations produced to liver endoplasmic reticulum by exposure in vivo or vitro to CC1 4 include covalent binding and lipid peroxidation; studies of these processes occurring during CC1 4 intoxication have uncovered a number of concepts of general relevance to free-radical mediated tissue injury. Lipid peroxidation produces a variety of substances that have high biological activities, including effects on cell division; many liver tumours have a much reduced rate of lipid peroxidation compared with normal liver. A discussion of this rather general feature of liver tumours is given in relation to the liver cell division that follows partial hepatectomy.

Halothane-dependent Lipid Peroxidation in Human Liver Microsomes Is Catalyzed by Cytochrome P4502A6 (CYP2A6)

2001 ◽  
Vol 95 (2) ◽  
pp. 509-514 ◽  
Author(s):  
Yuko Minoda ◽  
Evan D. Kharasch
Keyword(s):  
Lipid Peroxidation ◽  
Free Radical ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Gas Chromatography Mass Spectrometry ◽  
Rat Liver Microsomes ◽  
Low Oxygen

Background Halothane is extensively (approximately 50%) metabolized in humans and undergoes both oxidative and reductive cytochrome P450-catalyzed hepatic biotransformation. Halothane is reduced under low oxygen tensions by CYP2A6 and CYP3A4 in human liver microsome to an unstable free radical, and then to the volatile metabolites chlorodifluoroethene (CDE) and chlorotrifluoroethane (CTE). The free radical is also thought to initiate lipid peroxidation. Halothane-dependent lipid peroxidation has been shown in animals in vitro and in vivo but has not been evaluated in humans. This investigation tested the hypothesis that halothane causes lipid peroxidation in human liver microsomes, identified P450 isoforms responsible for halothane-dependent lipid peroxidation, and tested the hypothesis that lipid peroxidation is prevented by inhibiting halothane reduction. Methods Halothane metabolism was determined using human liver microsomes or cDNA-expressed P450. Lipid peroxidation was quantified by malondialdehyde (MDA) formation using high-pressure liquid chromatography-ultraviolet analysis of the thiobarbituric acid-MDA adduct. CTE and CDE were determined by gas chromatography-mass spectrometry. Results Halothane caused MDA formation in human liver microsomes at rates much lower than in rat liver microsomes. Human liver microsomal MDA production exhibited biphasic enzyme kinetics, similar to CDE and CTE production. MDA production was inhibited by the CYP2A6 inhibitor methoxsalen but not by the CYP3A4 inhibitor troleandomycin. Halothane-dependent MDA production was catalyzed by cDNA-expressed CYP2A6 but not CYP3A4 or P450 reductase alone. CYP2A6-catalyzed MDA production was inhibited by methoxsalen or anti-CYP2A6 antibody. Conclusions Halothane causes lipid peroxidation in human liver microsomes, which is catalyzed by CYP2A6, and inhibition of halothane reduction prevents halothane-dependent lipid peroxidation in vitro.

The Venom of the Boomslang (Dispholidus Typus): In Vivo and in Vitro Studies

1969 ◽  
Vol 21 (02) ◽  
pp. 234-244 ◽  
Author(s):  
N Mackay ◽  
J.C Ferguson ◽  
Antonia Bagshawe ◽  
A.T.T Forrester ◽  
G.P Mcnicol
Keyword(s):  
In Vitro Studies

SummaryAn account is given of the effects of boomslang venom in man. Evidence was found of a fibrinolytic state apparently secondary to the coagulant action of the venom. These features rapidly responded to the administration of specific antivenom. In vitro studies, using a homogenate of boomslang parotids, confirmed the coagulant properties of the venom and showed them to be of much greater potency than the proteolytic actions.

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