Liver covalent binding

Duverger-van Bogaert M, Lambotte-Vandepaer M, Mercier M, et al. 1982a. In vitro covalent binding of acrylonitrile to rat liver proteins. Toxicol Lett 13 203-209. 

Varanasi, U. and D.J. Gmur. 1980. Metabolic activation and covalent binding of benzo[a]pyrene to deoxyribonucleic acid catalyzed by liver enzymes of marine fish. Biochem. Pharmacol. 29 753-762. 

Roy, D. and Snodgrass W.R. 1990. Covalent binding of phenytoin to protein and modulation of phenytoin metabolism by thiols in A/J mouse liver microsomes. J. Pharmacol. Exp. Ther. 252 895. 

Cribb AE, Nuss CE, Alberts DW, et al. Covalent binding of sulfamethoxazole reactive metabolites to human and rat liver subcellular fractions assessed by immunochemical detection. Chem Res Toxicol 1996 9(2) 500-507. 

Cytochrome P-450 spectra (reduced + CO) show the 2-nm shift to the blue as a result of 3-MC induction. No such shift is observed in the trout, control rat, and PB-induced rat liver microsomes. Cytochrome P-450 EtNC spectra were recorded at pH 7.4, 2 min after the samples were reduced with dithionite. The absorption peaks are at 430 and 455 nm. For pH curves the A Absorbance represents A A (430—490 nm) and A A (455— 490 nm). The number of (+) signifies only the relative activity or inhibition with respect to BP hydroxylation and covalent binding of BP to DNA ( ++-(-) signifies 2-4 times and (+-H—h) signifies 10-36 times the control rat microsomal activity (n.d.), not determined. 

It has been noted that cell cultures derived from trout (66, 67) and trout liver microsomes (U2, U7, 68) may have relatively high AHH activity (BP hydroxylase) which sometimes exceeds the activity observed in control rat liver microsomes. The metabolite pattern obtained using trout liver microsomes resembled that produced by MC treated rat liver microsomes (P-Uh8)(6 and Ahokas, Saarni, Nebert and Pelkonen, manuscript in preparation Table IV). Associated with this pattern of BP metabolites was covalent binding to DNA which was three times as high as obtained by using rat liver microsomes. Another species of fish (roach), on the other hand was found to be almost inactive in catalyzing in vitro bind-... 

The in vitro metabolism and covalent binding of benzo(a) pyrene to DNA catalysed by trout liver microsomes. 

M. Wang, R. G. Dickinson, Disposition and Covalent Binding of Diflunisal and Diflunisal Acyl Glucuronide in the Isolated Perfused Rat Liver , Drug Metab. Dispos. 1998, 26, 98 - 104. 

Hepatocellular necrosis related to covalent binding of metabolites to cell and plasma proteins and to mitochondrial membrane damage results in release of intracellular enzymes into the bloodstream, providing biomarkers of liver cell damage. Biomarkers of hepatocellular necrosis are not specific to... 

After whole-body autoradiography to study the distribution of " C-labeled chloroform in mice, most of the radioactivity was found in fat immediately after exposure, while the concentration of radioactivity in the liver increased during the postanesthetic period, most likely due to covalent binding to lipid and protein in the liver (Cohen and Hood 1969). Partition coefilcients (tissue/air) for mice and rats were 21.3 and 20.8 for blood 19.1 and 21.1 for liver 11 and 11 for kidney and 242 and 203 for fat, respectively (Corley et al. 1990). Arterial levels of chloroform in mongrel dogs reached 0.35-0.40 mg/mL by the time animals were in deep anesthesia (Chenoweth et al. 1962). Chloroform concentrations in the inhaled stream were not measured, however. After 2.5 hours of deep anesthesia, there were 392 mg/kg chloroform in brain tissue, 1,305 mg/kg in adrenals, 2,820 mg/kg in omental fat, and 290 mg/kg in the liver. 

The mechanism of benzene-induced toxicity appears to involve the concerted action of several benzene metabolites. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and opened-ring products that are transported to the bone marrow, where secondary metabolism occurs. Metabolites may induce toxicity both by covalent binding to cellular macromolecules and by inducing oxidative damage. Metabolites may also inhibit stromal cells, which are necessary to support growth of differentiating and maturing marrow cells. ... 

In male and female rats exposed to 10, 50, 250, or 12 50 ppm vinyl bromide in a lifetime inhalation study, there was a dose-related increase in angiosarcomas of the liver in both sexes. A significant increase in hepatocellular neoplasms was also seen in male rats exposed at 250ppm and in female rats exposed at 10, 50, and 250ppm. The lack of increase in hepatocellular neoplasms in rats at the 12 50 ppm level was probably due to their early mortality and termination at 72 weeks. In limited mice studies, no local tumors were produced by skin application or subcutaneous administration. Vinyl bromide is mutagenic in bacterial assays and Drosophilas It is activated via a P-450-dependent pathway to its epoxide that can covalently bind to DNA. ... 

Studies in mice have shown that selective covalent binding of VDC occurs in the proximal tubules, the liver lobules, and the mucosa of the upper respiratory tract and corresponds to sites of potential toxicity. Additional events such as depletion of glutathione appear to be necessary for VDC-induced cell death to occur. 

Typically, the extent of covalent binding of microsomal protein may be evaluated by incubating or -labeled dmg substance with liver microsomes in the presence... 

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. 

Relative importance of covalent binding and lipid peroxidation in carbon tetrachloride-induced liver toxicity role of cell calcuim, protein and phospholipid degradation development of treatments/ antidotes. 

Becker E, Messner B, Berndt J. 1987. Two mechanisms of CCK induced fatty liver lipid peroxidation or covalent binding studied in cultured rat hepatocytes. Free Rad Res Commun 3 299- 308. 

Diaz Gomez Ml, Castro JA. 1980a. Covalent binding of carbon tetrachloride metabolites to liver nuclear DNA, proteins and lipids. Toxicol AppI Pharmacol 56 199-206. 

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