Metabolic Activation of Carbon Tetrachloride to a Free-Radical Product: Studies using a Spin Trap

1978 ◽  
Vol 6 (5) ◽  
pp. 962-964 ◽  
Author(s):  
A. INGALL ◽  
K. A. K. LOTT ◽  
T. F. SLATER ◽  
S. FINCH ◽  
A. STIER
Keyword(s):  
Free Radical ◽  
Carbon Tetrachloride ◽  
Spin Trap ◽  
Metabolic Activation ◽  
Radical Product ◽  
Free Radical Product

scholarly journals Spin-trapping studies on the free-radical products formed by metabolic activation of carbon tetrachloride in rat liver microsomal fractions isolated hepatocytes and in vivo in the rat

1982 ◽  
Vol 204 (2) ◽  
pp. 593-603 ◽  
Author(s):  
E Albano ◽  
K A K Lott ◽  
T F Slater ◽  
A Stier ◽  
M C R Symons ◽  
...  
Keyword(s):  
Free Radical ◽  
Carbon Tetrachloride ◽  
Spin Trap ◽  
Peroxy Radical ◽  
Metabolic Activation ◽  
Spin Trapping ◽  
Metabolic Inhibitors ◽  
Radical Species ◽  
Free Radical Species ◽  
Trichloromethyl Radical

1. The metabolic activation of carbon tetrachloride to free-radical intermediates is an important step in the sequence of disturbances leading to the acute liver injury produced by this toxic agent. Electron-spin-resonance (e.s.r.) spin-trapping techniques were used to characterize the free-radical species involved. 2. Spin trapping was applied to the activation of carbon tetrachloride by liver microsomal fractions in the presence of NADPH, and by isolated intact rat hepatocytes. The results obtained with the spin trap N-benzylidene-2-methylpropylamine N-oxide (‘phenyl t-butyl nitrone’) (PBN) and [13C]carbon tetrachloride provide unequivocal evidence for the formation and trapping of the trichloromethyl free radical in these systems. 3. With the spin trap 2-methyl-2-nitrosopropane, however, the major free-radical species trapped are unsaturated lipid radicals produced by the initiating reaction of lipid peroxidation. 4. Although pulse radiolysis and other evidence support the very rapid formation of the trichloromethyl peroxy radical from the trichloromethyl radical and oxygen, no clear evidence for the trapping of the peroxy radical was obtainable. 5. The effects of a number of free-radical scavengers and metabolic inhibitors on the formation of the PBN-trichloromethyl radical adduct were studied, as were the influences of changing the concentration of PBN and incubation time. 6. High concentrations of the spin traps used were found to have significant effects on cytochrome P-450-mediated reactions; this requires caution in interpreting results of experiments done in the presence of PBN at concentrations greater than 50 mM.

The alkoxy radical, RCH2Ȯ, as a free radical product in x-irradiated single crystals of nucleosides and nucleotides

1977 ◽  
Vol 67 (3) ◽  
pp. 1211 ◽  
Author(s):  
William A. Bernhard ◽  
David M. Close ◽  
Jürgen Hüttermann ◽  
Herbert Zehner
Keyword(s):  
Free Radical ◽  
Single Crystals ◽  
Alkoxy Radical ◽  
Radical Product ◽  
Free Radical Product

Radical reactions of nitric oxide synthases

2004 ◽  
Vol 71 ◽  
pp. 39-49 ◽  
Author(s):  
Dennis J. Stuehr ◽  
Chin-Chuan Wei ◽  
Jerome Santolini ◽  
Zhi- Qiang Wang ◽  
Mika Aoyagi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electron Transfer ◽  
Free Radical ◽  
Structural Features ◽  
Nitric Oxide Synthases ◽  
Radical Reactions ◽  
Radical Product ◽  
O2 Activation ◽  
Health And Disease ◽  
Free Radical Product

NOSs (nitric oxide synthases) are flavohaem enzymes that function broadly in human health and disease. We are combining mutagenesis, crystallographic and rapid kinetic methods to understand their mechanism and regulation. The NOSs create a transient tetrahydrobiopterin radical within the enzyme to generate their free radical product (NO). Recent work is revealing how critically important this process is at all levels of catalysis. This article will synthesize four seemingly disparate but related aspects of NOS tetrahydrobiopterin radical formation: (i) how it enables productive O2 activation by providing an electron to the enzyme haem, (ii) what structural features help to regulate this electron transfer, (iii) how it enables NOS to synthesize NO from its diamagnetic substrate and (iv) how it allows NOS to release NO after each catalytic cycle instead of other nitorgen oxide-containing products.

FREE RADICAL PRODUCT FORMED BY THE REACTION OF DEHYDROASCORBIC ACID WITH AMINO ACIDS

1974 ◽  
Vol 3 (2) ◽  
pp. 125-128 ◽  
Author(s):  
Mitsuo Namiki ◽  
Midori Yano ◽  
Tateki Hayashi
Keyword(s):  
Amino Acids ◽  
Free Radical ◽  
Dehydroascorbic Acid ◽  
Radical Product ◽  
Free Radical Product

Effect of 1,3,6-trimethyl-5-hydroxyuracil succinate on the antioxidant system and free-radical processes in the liver of adult and old rats treated with carbon tetrachloride

2018 ◽  
pp. 55-59
Author(s):  
И.Д. Габдрахманова ◽  
В.А. Мышкин ◽  
Д.А. Еникеев ◽  
А.Р. Гимадиева
Keyword(s):  
Superoxide Dismutase ◽  
Free Radical ◽  
Carbon Tetrachloride ◽  
Antioxidant System ◽  
Complex Compound ◽  
Antiradical Activity ◽  
Conjugated Dienes ◽  
Experimental Animals ◽  
Old Rats ◽  
Radical Processes

Цель исследования: изучение влияния сукцината 1,3,6-триметил-5-гидроксиурацила на антиоксидантную систему и свободнорадикальные процессы в печени взрослых и старых крыс при воздействии тетрахлорметана. Методика. В эксперименте использованы половозрелые животные 12-месячного возраста со средней массой 250 г и старые животные 24-месячного возраста, средней массой 395 г по 30 особей в каждой возрастной группе. Токсическое поражение печени вызывали подкожным введением 50%-ного масляного раствора тетрахлорметана (ТХМ, 2 г/кг) в течение 4 сут. Одновременно с токсикантом опытным животным внутрибрюшинно вводили водный раствор коплексного соединения сукцинат-1,3,6-триметил-5-гидроксиурацила (2,5 мг/100 г) 3 раза в сут. в течение первых 4 сут. и в течение последующих 3 сут. 1 раз в сут. Контролем служили опытные животные, которым вводили физиологический раствор в том же объеме. Изучали окислительную модификацию белков, перекисное окисление липидов (по содержанию ТБК-реагирующих продуктов, уровню гидроперекисей липидов и содержанию диеновых конъюгатов). Состояние антиоксидантной системы оценивали по активности ферментов супероксиддисмутазы, каталазы и глутатионпероксидазы, определяемых биохимическими методами. Антирадикальную активность комплексного соединения и его составляющих субстанций исследовали в модельной системе «этилбензол-ледяная уксусная кислота» с вычислением константы К - скорости взаимодействия перекисных радикалов с молекулами изучаемого соединения в сравнении с эталонным антиоксидантом-ионолом с витамином Е. Результаты. Сукцинат + 1,3,6-триметил-5-гидрокси-урацила существенно снижает токсическое действие ТХМ на печень взрослых и старых крыс, устраняет дисбаланс в системах свободнорадикального окисления белков у старых крыс, статистически значимо улучшает показатели свободнорадикального окисления (СРО) липидов в печени взрослых и старых крыс: снижает уровень продуктов ПОЛ - гидроперекисей, диеновых конъюгатов, ТБК-реагирующих продуктов, а также улучшает работу антиоксидантной системы (АОС), повышая активность каталазы, супероксиддисмутазы и глутатионпероксидазы. Установлена высокая антирадикальная активность изучаемого препарата сопоставимая с активностью эталонного антиоксиданта ионола. Заключение. Сукцинат и его производные способны выступать как индивидуальные вещества с непосредственным антирадикальным механизмом действия, а не только как стимуляторы ферментативных систем антиоксидантной защиты. Aim. To study the effect of a complex compound, 1,3,6-trimethyl-5-hydroxyuracil succinate, on the antioxidant system and free radical processes induced by carbon tetrachloride in the liver of adult and old rats. Methods. The study used sexually mature animals aged 12 months and weighing 250 g and old animals aged 24 months weighing 395 g (total n= 60, 30 rats in each age group). Toxic damage of liver was induced by subcutaneous injections of a 50% oil solution of carbon tetrachloride (CTC) at 2 g/kg for 4 days. Together with the toxicant, experimental animals were injected with a water solution of a complex compound, succinate 1,3,6-trimethyl-5-hydroxyuracil, at a dose of 2.5 mg/100 g, i.p., 3 times per day for the first 4 days and once daily for the following 3 days. Experimental animals were used as controls, which were administered saline in the same volume. Oxidative modifications of proteins, lipid peroxidation (by levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, and conjugated dienes) were studied. Condition of the antioxidant system was evaluated by activities of superoxide dismutase, catalase, and glutathione peroxidase using biochemical methods. Antiradical activity of the complex compound and its components was studied in a model system of ethylbenzene-glacial acetic acid; the K7 constant of the rate of peroxide radical interaction with molecules of the studied compound was compared with the reference antioxidant ionol with vitamin E. Results. Succinate +1.3.6-trimethyl-5-hydroxyuracil, considerably reduced TXM hepatotoxicity in adult and old rats; removed the disbalance in free radical systems of protein oxidation in old rats; significantly improved indexes of free-radical oxidation (FRO) of hepatic lipids in adult and old rats; decreased levels of LP products, hydroperoxides, conjugated dienes, and TBARS, and enhanced performance of the antioxidant system (AOS) by increasing activities of catalase, superoxide dismutase, and glutathione peroxidase. The study demonstrated a high antiradical activity of the study drug comparable with the activity of the reference antioxidant, ionol. Сonclusion. Succinate and its derivatives can perform as individual substances with a direct antiradical mechanism of action rather than as stimulators of enzymic systems of antioxidant defence.

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