NADPH-dependent microsomal

Thus, superoxide itself is obviously too inert to be a direct initiator of lipid peroxidation. However, it may be converted into some reactive species in superoxide-dependent oxidative processes. It has been suggested that superoxide can initiate lipid peroxidation by reducing ferric into ferrous iron, which is able to catalyze the formation of free hydroxyl radicals via the Fenton reaction. The possibility of hydroxyl-initiated lipid peroxidation was considered in earlier studies. For example, Lai and Piette [8] identified hydroxyl radicals in NADPH-dependent microsomal lipid peroxidation by EPR spectroscopy using the spin-trapping agents DMPO and phenyl-tcrt-butylnitrone. They proposed that hydroxyl radicals are generated by the Fenton reaction between ferrous ions and hydrogen peroxide formed by the dismutation of superoxide. Later on, the formation of hydroxyl radicals was shown in the oxidation of NADPH catalyzed by microsomal NADPH-cytochrome P-450 reductase [9,10]. 

In 1989, we showed [142] that the Fe2+(rutin)2 complex is a more effective inhibitor than rutin of asbestos-induced erythrocyte hemolysis and asbestos-stimulated oxygen radical production by rat peritoneal macrophages. Later on, to evaluate the mechanisms of antioxidant activities of iron rutin and copper-rutin complexes, we compared the effects of these complexes on iron-dependent liposomal and microsomal lipid peroxidation [165], It was found that the iron rutin complex was by two to three times a more efficient inhibitor of liposomal peroxidation than the copper-rutin complex, while the opposite tendency was observed in NADPH-dependent microsomal peroxidation. On the other hand, the copper rutin complex was much more effective than the iron rutin complex in the suppression of microsomal superoxide production, indicating that the copper rutin complex indeed acquired additional SOD-dismuting activity because superoxide is an initiator of NADPH-dependent... 

In addition the rate of NADPH-dependent microsomal lipoperoxidation was higher in... 

Figure 12. The NADPH-dependent microsomal lipoperoxidation in the isolated rabbit hepatocytes from animals which fed during 6 weeks with diet without cholesterol (1), and with cholesterol preparation which contain about 5% oxysterols (2) and with purified cholesterol (3).

Biorcduction of nitro compounds is carried out by NADPH-dependent microsomal and soluble nitro reductases present in the liver. A multicomponent hepatic microsomal reductase system requiring NADPH appears to be responsible for azo reduction. " " In addition, bacterial reductases present in the intestine can reduce nitro and azo compounds, especially those that are absorbed poorly or excreted mainly in the bile. - ... 

Misra HP, Rabideau C. 2000. Pirfenidone inhibits NADPH-dependent microsomal lipid peroxidation and scavenges hydroxyl radicals. Mol. Cell Biochem. 204 119-26... 

Minakami H, Arai H, Nakano M, Sugioka K, Suzuki S, Sotomatsu A. A new and suitable reconstructed system for NADPH-dependent microsomal lipid peroxidation. Biochem Biophys Res Commun 1988 153 973-8. 

GoasduffT. and A.I. Cederbaum (1999). NADPH-dependent microsomal electron transfer increases degradation of CYP2E1 by the proteasome complex Role of reactive oxygen species. Arch. Biochem. Biophys. 370, 258-270. 

Capdevila, J., P. Mosset, P. Yadagiri, Sun Lumin, and J.R. Falck (1988). NADPH-Dependent microsomal metabolism of 14,15-epoxyeicosatrienoic acid to diepoxides and epoxyalcohols. Arch. Biochem. Biophys. 261, 122-132. 

Nakagawa, K. et al.. Inhibition by P-carotene and astaxanthin of NADPH-dependent microsomal phospholipid peroxidation, J. Nutr. Set Vitaminol, 43, 345,1997. 

Fontecave, M., Mansuy, D., Jaouen, M. and Pezerat, H. (1987). The stimulator) effects of asbestos on NADPH-dependent lipid peroxidation in rat liver microsomes. Biochem. J. 241, 561-565. 

Superoxide generation was detected via the NADPH-dependent SOD-inhibitable epinephrine oxidation and spin trapping [15,16], Grover and Piette [17] proposed that superoxide is produced equally by both FAD and FMN of cytochrome P-450 reductase. However, from comparison of the reduction potentials of FAD (-328 mV) and FMN (190 mV) one might expect FAD to be the most efficient superoxide producer. Recently, the importance of the microsomal cytochrome h558 reductase-catalyzed superoxide production has been shown in bovine cardiac myocytes [18]. 

Values (p.mol I-1) of Flavonoids and BHT for the Inhibition of NADPH-Dependent- (I) and CCI4-Dependent (II) Microsomal Lipid Peroxidation... 

This mechanism is now considered to be of importance for the protection of LDL against oxidation stress, Chapter 25.) The antioxidant effect of ubiquinones on lipid peroxidation was first shown in 1980 [237]. In 1987 Solaini et al. [238] showed that the depletion of beef heart mitochondria from ubiquinone enhanced the iron adriamycin-initiated lipid peroxidation whereas the reincorporation of ubiquinone in mitochondria depressed lipid peroxidation. It was concluded that ubiquinone is able to protect mitochondria against the prooxidant effect of adriamycin. Inhibition of in vitro and in vivo liposomal, microsomal, and mitochondrial lipid peroxidation has also been shown in studies by Beyer [239] and Frei et al. [240]. Later on, it was suggested that ubihydroquinones inhibit lipid peroxidation only in cooperation with vitamin E [241]. However, simultaneous presence of ubihydroquinone and vitamin E apparently is not always necessary [242], although the synergistic interaction of these antioxidants may take place (see below). It has been shown that the enzymatic reduction of ubiquinones to ubihydroquinones is catalyzed by NADH-dependent plasma membrane reductase and NADPH-dependent cytosolic ubiquinone reductase [243,244]. 

The species differences in biotransformation pathways, rates of elimination, and intrinsic hepatic clearance of esfenvalerate and deltamethrin using rat and human liver microsomes were examined [33]. Esfenvalerate was eliminated primarily via NADPH-dependent oxidative metabolism in both rat and human liver microsomes. The CLint of esfenvalerate was estimated to be threefold greater in rodents than in humans on a per kg body weight basis. Deltamethrin was also eliminated primarily via NADPH-dependent oxidative metabolism in rat liver microsomes however, in human liver microsomes, deltamethrin was eliminated almost entirely via... 

Servent and colleagues [52] reported that GTN is metabolised in rat liver microsomes by an NADPH-dependent cytochrome P-450 system, yielding GDN, glyceryl mononitrate (GMN) and NO. Moreover, Schroeder and Schroer [53] showed that inhibitors of cytochrome P-450 reduce cGMP stimulation by GTN in kidney epithelial cells. 

Cytochrome P-450 systems are also present in both smooth muscle [54, 5 5] and endothelial [56] cells. In studies of hepatic [57] and aortic [58] microsomes, Bennett and colleagues showed that bioconversion of GTN to GDN was NADPH dependent and was inhibited by the cytochrome P-450 inhibitor, SKF 525A. In hepatic microsomes, moreover, conversion of GTN led to activation of sGC [59]. 

Table I). The levels of both, cytochrome P-L50 (Table i) and its NADPH (reduced nicotinamide adenine dinucleotide phosphate) requiring reducing component (Figure l)(which can be measured as NADPH dependent cytochrome c reductase) are substantial in fish liver microsomes, although lower than in mammals. NADPH cytochrome c reductase level in trout Salmo trutta lacustris) is 20 nmol cytochrome c reduced/mg microsomal protein/min the corresponding activity in male Sprague Dawley rat liver microsomes is 96 nmol cytochrome c reduced/mg microsomal protein/min (lU). 

Zhao, S.X. et al. (2007) NADPH-dependent covalent binding of [3H] paroxetine to human liver microsomes and S-9 fractions identification of an electrophilic quinone metabolite of paroxetine. Chemical Research in Toxicology, 20 (11), 1649-1657. 

The NADPH-dependent metabolism of a PBB mixture was studied in vitro with liver microsomes of rats induced with PB, PBB, or 3-MC (Dannan et al. 1978a). Of the 12 major components of the mixture, only 2,2, 4,5,5 -pentabromobiphenyl and a hexabromobiphenyl were metabolized by microsomes Ifom PB- or... 

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