Chemico-biological interactions
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Chem. Biol. Interact. · Apr 1998
Glutathione S-transferases as biomarkers of organ damage: applications of rodent and canine GST enzyme immunoassays.
The cytosolic glutathione S-transferase (GST) enzymes serve as ideal biomarkers of organ damage as they exhibit many of the required characteristics, i.e. specific localisation, high cytosolic concentration and relatively short half-life. The role of GSTs as early indicators of organ damage is applicable to both human and animal models. Because of the regio-specific localisation of the different isoforms of GST in liver and kidney, simultaneous monitoring of classes of GSTs in biological matrices permits the identification of specific areas of damage within a particular organ. ⋯ No prozone effect was observed and samples exhibited linearity of dilution in both assays. Validation has shown that using these enzyme immunoassay, Yb1 and canine alpha GST can be measured accurately and precisely in biological matrices, tissue homogenates and cell lines and that changes in GST levels can be detected. The use of these assays have important applications in both in vitro and in vivo toxicity studies, where GST's serve as sensitive marker of hepatocellular and renal cell integrity.
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Chem. Biol. Interact. · Dec 1996
Formation of reactive oxygen species and DNA strand breakage during interaction of chromium (III) and hydrogen peroxide in vitro: evidence for a chromium (III)-mediated Fenton-like reaction.
The role of reactive oxygen species in causing DNA damage through interaction of chromium (III) and hydrogen peroxide was examined using plasmid relaxation assay and EPR spectroscopy. Marked DNA strand breakage was induced by CrCl3 plus H2O2 in a phosphate buffer at pH 6-8.9; whereas, only slight DNA strand breakage was observed during similar treatment at pH less than 4. DNA breakage also increased as the reaction temperature and Cr(III)/H2O2 concentrations increased. ⋯ OH generated by Cr(III)/H2O2/DMPO; however, they were less efficient than ascorbate and no Cr(V) signals were detected. This study shows that Cr(III)/H2O2 generates oxidative damage to DNA through a Fenton-like reaction: Cr(III) + H2O2-->Cr(IV) +. OH + OH.
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Chem. Biol. Interact. · Jan 1988
Study on the mechanism of interference of 3,4,3',4'-tetrachlorobiphenyl with the plasma retinol-binding proteins in rodents.
The mechanism of plasma retinol reduction in rodents by 3,4,3',4'-tetrachlorobiphenyl (TCB) was investigated by radioimmunochemical analysis of the amounts of circulating and hepatic retinol-binding protein (RBP) and transthyretin (TTR) in exposed and control animals. Plasma RBP concentrations were markedly reduced in C57BL/Rij mice (50%) at 4 days, in DBA/2 mice (37-41%) at 4 and 8 days, and in Sprague-Dawley rats (58%) at 2 days after exposure to TCB. These reductions paralleled the time course of reduction of plasma retinol after exposure to TCB. ⋯ The dissociation constants of the RBP-TTR complex as analysed by polarization of fluorescence appeared to be significantly increased (from 0.5 x 10(-7) M-1 to 2.4 x 10(-7) M-1) in the presence of a TCB metabolite, isolated from plasma of TCB-treated rats. In addition, the estimated number of binding sites for RBP on the TTR molecule was reduced (from 2.8 to 1.7 sites) upon treatment of TTR with the TCB metabolite. These data support the hypothesis that plasma retinol reduction by TCB might result from a weakening of the RBP-TTR complex, in the presence of the TCB metabolite bound to the TTR.
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Chem. Biol. Interact. · Jul 1977
ReviewSome aspects of the mechanisms by which industrial solvents produce neurotoxic effects.
A Short Review is given of the biochemical neurotoxic mechanisms of common industrial solvents of various structures. The acute effects of organic solvents may be caused by their direct action on the nerve cell membrane and energy metabolism, whereas chronic neurotoxic effects may be explained by the formation of chemically and biologically reactive intermediates. The stability of the toxic metabolites appears to correlate with the development of neuropathy although this is structuredependent. The role of reactive intermediates is also emphasized by the potentiating effect of the induction of the cytochrome P-450 complex.