Free-Radical Mechanisms in Tissue Injury

Slater, T. F.

doi:10.1042/bst0030062

Cited by 193 publications

(233 citation statements)

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“…This is the first time direct evidence of free radical generation after KA insult has been demonstrated. Oxygen radicals have been shown to cause lipid peroxidation, damage to membranes, enzymes, and nucleic acids at the cellular and subcellular systems (Freeman and Crapo, 1982;Slater, 1984;Gutteridge and Halliwell, 1990). We have also demonstrated the damage of free radical to (Na`,K+)-ATPase activity in both in vitro (Sun, 1972;Oldfield et al, 1991) and in vivo (Fig.…”

Section: Damage Of Neuronal Membranementioning

confidence: 60%

The biochemical mechanisms of the excitotoxicity of Kainic acid

Sun

Cheng

et al. 1992

Molecular and Chemical Neuropathology

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Kainic acid (KA) is a known potent neuroexcitotoxin, although the biochemical mechanism producing its underlying neurotoxic effect is not quite clear. Histopathological examination of gerbil brains 24 h after systemic injection of KA revealed severe neuronal lesions in different regions of the brain, especially the cerebellar and hippocampal areas. We have detected free radical formation in the brain 1 h after KA administration by using an in vivo spin trapping technique. We have also observed increased lipid peroxidation in the brain after KA-treatment by analyzing thiobarbituric acid reactive substances and conjugated diene formation. Diminished brain specific (Na+, K+)-ATPase activity was also found 2 h after KA injection and persisted to 24 h. It is possible that the free radical reaction is a primary cause of neuronal degeneration after KA administration.

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Section: Damage Of Neuronal Membranementioning

confidence: 60%

The biochemical mechanisms of the excitotoxicity of Kainic acid

Sun

Cheng

et al. 1992

Molecular and Chemical Neuropathology

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“…A negative correlation between calcium and protein thiol content of the cell, observed in urolithic conditions, supports this [67]. It is true when the reactive oxygen species overwhelms cellular defenses [105]. Renal tubular cells are found to be highly susceptible to injury during periods of exogenous oxidative stress, and an association between depletion of oxidation of GSH pool and the onset of injury has been noted [61].…”

Section: Protein Damage By Thiol Oxidation and Calcium Accumulationmentioning

confidence: 76%

Calcium oxalate stone disease: role of lipid peroxidation and antioxidants

Selvam

2002

Urological Research

189

105

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Membrane injury facilitated the fixation of calcium oxalate crystals and subsequent growth into kidney stones. Oxalate-induced membrane injury was mediated by lipid peroxidation reaction through the generation of oxygen free radicals. In urolithic rat kidney or oxalate exposed cultured cells, both superoxide anion and hydroxyl radicals were generated in excess, causing cellular injury. In hyperoxaluric rat kidney, both superoxide and H2O2-generating enzymes such as glycolic acid oxidase (GAO) and xanthine oxidase (XO) were increased, and hydroxyl radical and transition metal ions, iron, and copper were accumulated. The lipid peroxidation products, thiobarbituric acid-reactive substances (TBARS), hydroperoxides, and diene conjugates were excessively released in tissues of urolithic rats and in plasma of rats as well as stone patients. The accumulation of these products was concomitant with the decrease in the antioxidant enzymes, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glucose-6 phosphate dehydrogenase (G6PD) as well as radical scavengers, vitamin E, ascorbic acid, reduced glutathione (GSH), and protein thiol. All the above parameters were decreased in urolithic condition, irrespective of the agents used for the induction of urolithiasis. Oxalate binding activity and calcium oxalate crystal deposition were markedly pronounced, along with decreased adenosine triphosphatase (ATPase) activity. Lipid peroxidation positively correlated with cellular oxalate, oxalate binding, gamma-glutamyl carboxylase, and calcium level and negatively correlated with GSH, vitamin E. ascorbic acid, and total protein thiol. Antioxidant therapy to urolithic rats with vitamin E, glutathione monoester, methionine, lipoic acid, or fish oil normalised the cellular antioxidant system, enzymes and scavengers, and interrupted membrane lipid and protein peroxidation reaction, ATPase inactivation, and its associated calcium accumulation. Antioxidant therapy prevented calcium oxalate precipitation in the rat kidney and reduced oxalate excretion in stone patients. Similarly, calcium oxalate crystal deposition in vitro to urothelium was prevented by free radical scavengers such as phytic acid and mannitol by protecting the membrane from free radical-mediated damage. All these observations were suggestive of the active involvement of free radical-mediated lipid peroxidation-induced membrane damage in the pathogenesis of calcium oxalate crystal deposition and retention.

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“…This activation of the cytochrome P450 system by senecionine, but not t-4HH, may explain the increased levels of TBARs observed with senecionine in Panel 1. It is known that the metabolism of many xenobiotics results in the formation of free radical intermediates (Slater, 1972). Compounds metabolized in the mixed function oxidase system utilizing the NADPHcytochrome P450 electron transport chain generate reactive oxygen species such as superoxides, hydrogen peroxide, the hydroxyl radical and singlet oxygen (Cojocel et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Lipid peroxidation and cellular damage caused by the pyrrolizidine alkaloid senecionine, the alkenal trans-4-hydroxy-2-hexenal, and related alkenals

Griffin

Segall

1987

Cell Biol Toxicol

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Lipid peroxidation was examined as a possible mechanism for cell injury by trans-4-OH-2-hexenal, the macrocyclic pyrrolizidine alkaloid senecionine and related alkenals in isolated rat hepatocytes. Each compound elicited a positive dose response for peroxidation of cellular lipids as measured by the formation of thiobarbituric acid-reactive products. The addition of the anti-oxidant N,N'-diphenyl-p-phenylenediamine to the hepatocyte suspensions inhibited the production of thiobarbituric acid-reactants. However, the presence of the anti-oxidant had no protective effects on the cell membrane integrity as evidenced by the leakage of lactate dehydrogenase from the cells into the surrounding media. These results suggest that lipid peroxidation which occurs in the presence of senecionine, trans-4-OH-2-hexenal or related alkenals is not entirely responsible for the cellular damage in isolated rat hepatocytes.

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Free-Radical Mechanisms in Tissue Injury

Cited by 193 publications

References 0 publications

The biochemical mechanisms of the excitotoxicity of Kainic acid

The biochemical mechanisms of the excitotoxicity of Kainic acid

Calcium oxalate stone disease: role of lipid peroxidation and antioxidants

Lipid peroxidation and cellular damage caused by the pyrrolizidine alkaloid senecionine, the alkenal trans-4-hydroxy-2-hexenal, and related alkenals

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