Journal of Biochemical and Molecular Toxicology 

About: Journal of Biochemical and Molecular Toxicology is an academic journal published by Wiley. The journal publishes majorly in the area(s): Medicine & Oxidative stress. It has an ISSN identifier of 1095-6670. Over the lifetime, 2359 publications have been published receiving 41683 citations. The journal is also known as: Biochemical and molecular toxicology.

Diabetes, oxidative stress, and antioxidants: a review

Abstract: Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options.

Mechanisms of cadmium‐mediated acute hepatotoxicity

Abstract: The mechanism of cadmium-mediated acute hepatotoxicity has been the subject of numerous investigations and although some uncertainties persist, sufficient evidence has emerged to provide a reasonable account of the toxic process. Acute hepatotoxicity involves two pathways, one for the initial injury produced by direct effects of cadmium and the other for the subsequent injury produced by inflammation. Primary injury appears to be caused by the binding of Cd2+ to sulfhydryl groups on critical molecules in mitochondria. Thiol group inactivation causes oxidative stress, the mitochondrial permeability transition, and mitochondrial dysfunction. Although cadmium may injure hepatocytes directly, there are compelling reasons to believe that hepatocellular injury is produced in vivo as the result of ischemia caused by damage to endothelial cells. Secondary injury from acute cadmium exposure is thought to occur from the activation of Kupffer cells and a cascade of events involving several types of liver cells and a large number of inflammatory and cytotoxic mediators. In this regard, it is clear that Kupffer cell activation and neutrophil infiltration are important events in the toxic process, and the involvement of proinflammatory cytokines and chemokines has also been implicated. The precise roles of the soluble mediators of inflammation warrant further investigation.

Human aldehyde dehydrogenases: potential pathological, pharmacological, and toxicological impact.

Abstract: Aldehyde dehydrogenases catalyze the pyridine nucleotide-dependent oxidation of aldehydes to acids. Seventeen enzymes are currently viewed as belonging to the human aldehyde dehydrogenase superfamily. Summarized herein, insofar as the information is available, are the structural composition, physical properties, tissue distribution, subcellular location, substrate specificity, and cofactor preference of each member of this superfamily. Also summarized are the chromosomal locations and organization of the genes that encode these enzymes and the biological consequences when enzyme activity is lost or substantially diminished. Broadly, aldehyde dehydrogenases can be categorized as critical for normal development and/or physiological homeostasis (1) even when the organism is in a friendly environment or (2) only when the organism finds itself in a hostile environment. The primary, if not sole, evolved raison d'etre of first category aldehyde dehydrogenases appears to be to catalyze the biotransformation of a single endobiotic for which they are relatively specific and of which the resultant metabolite is essential to the organism. Most of the human aldehyde dehydrogenases for which the relevant information is available fall into this category. Second category aldehyde dehydrogenases are relatively substrate nonspecific and their evolved raison d'etre seems to be to protect the organism from potentially harmful xenobiotics, specifically aldehydes or xenobiotics that give rise to aldehydes, by catalyzing their detoxification. Thus, the lack of a fully functional first category aldehyde dehydrogenase results in a gross pathological phenotype in the absence of any insult, whereas the lack of a functional second category aldehyde dehydrogenase is ordinarily of no consequence with respect to gross phenotype, but is of consequence in that regard when the organism is subjected to a relevant insult. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:7–23, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10057

Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster® 550 in rats: an exploratory assessment.

Abstract: Firemaster® 550 (FM 550), a fire-retardant mixture used in foam-based products, was recently identified as a common contaminant in household dust. The chemical structures of its principle components suggest they have endocrine disrupting activity, but nothing is known about their physiological effects at environmentally relevant exposure levels. The goal of this exploratory study was to evaluate accumulation, metabolism and endocrine disrupting effects of FM 550 in rats exposed to 100 or 1000 µg/day across gestation and lactation. FM 550 components accumulated in tissues of exposed dams and offspring and induced phenotypic hallmarks associated with metabolic syndrome in the offspring. Effects included increased serum thyroxine levels and reduced hepatic carboxylesterease activity in dams, and advanced female puberty, weight gain, male cardiac hypertrophy, and altered exploratory behaviors in offspring. Results of this study are the first to implicate FM 550 as an endocrine disruptor and an obesogen at environmentally relevant levels.

Response of the antioxidant defense system to tert-butyl hydroperoxide and hydrogen peroxide in a human hepatoma cell line (HepG2).

Abstract: The aim of this work was to investigate the response of the antioxidant defense system to two oxidative stressors, hydrogen peroxide and tert-butyl hydroperoxide, in HepG2 cells in culture. The parameters evaluated included enzyme activity and gene expression of superoxide dismutase, catalase, glutathione peroxidase, and activity of glutathione reductase. Besides, markers of the cell damage and oxidative stress evoked by the stressors such as cell viability, intracellular reactive oxygen species generation, malondialdehyde levels, and reduced glutathione concentration were evaluated. Both stressors, hydrogen peroxide and tert-butyl hydroperoxide, enhanced cell damage and reactive oxygen species generation at doses above 50 microM. The concentration of reduced glutathione decreased, and levels of malondialdehyde and activity of the antioxidant enzymes consistently increased only when HepG2 cells were treated with tert-butyl hydroperoxide but not when hydrogen peroxide was used. A slight increase in the gene expression of Cu/Zn superoxide dismutase and catalase with 500 microM tert-butyl hydroperoxide and of catalase with 200 microM hydrogen peroxide was observed. The response of the components of the antioxidant defense system evaluated in this study indicates that tert-butyl hydroperoxide evokes a consistent cellular stress in HepG2.