Disease relevance of bromobenzene

• The mechanisms of bromobenzene toxicity in extrahepatic tissues of mice were studied [1].
• LCA injection induced cholestasis of comparable amplitude in both control and BZ-treated rats [2].
• MEASUREMENTS AND MAIN RESULTS: After the decapitation, the specific gravities of the neocortex, caudatoputamen, hippocampus, cerebellum, and midbrain were measured using a variable-density bromobenzene-kerosene column technique as an index of brain swelling [3].
• Likewise, hyperthyroidism did not enhance the hepatotoxicity of another hepatotoxin bromobenzene [4].
• Bromobenzene alone caused a significant, dose-related hypothermia [5].

High impact information on bromobenzene

• Bromobenzene accelerates hepatocyte streaming in rats [6].
• Subliminal Fas stimulation increases the hepatotoxicity of acetaminophen and bromobenzene in mice [7].
• In mice pretreated with the Jo2 antibody before bromobenzene administration, hepatic GSH 4 hours after bromobenzene administration was 51% lower than in mice treated with bromobenzene alone, and serum ALT activity at 24 hours was 47-fold higher [7].
• In this study, the effect of GSH depletion on the Met pool and methylation capability was examined after bromobenzene (BB), a model GSH-depleting hepatotoxin, was administered to the Syrian hamster [8].
• Heme oxygenase appeared to be the HO-1 form, an assignment based on its amino acid sequence matching the sequence of 2 peptides obtained from purified HO-1 and the immunochemical properties of the cobalt-, hematin-, and bromobenzene-induced rat liver enzyme [9].

Chemical compound and disease context of bromobenzene

• In such animals, bromobenzene and allyl alcohol had only limited toxicity and diethylmaleate none in spite of comparable hepatic GSH depletion [10].
• Cellular toxicity of bromobenzene and bromobenzene metabolites to rabbit proximal tubules: the role and mechanism of 2-bromohydroquinone [11].
• To assess this hypothesis, we determined the effects of this prostaglandin on the metabolism and toxicity of bromobenzene in mice [12].
• Carbon tetrachloride and bromobenzene also failed to produce blebs at lethal concentrations [13].
• Metabolic activation and hepatotoxicity. Toxicity of bromobenzene in hepatocytes isolated from phenobarbital-and diethylmaleate-treated rats [14].

Biological context of bromobenzene

• Histochemical detection of lipid peroxidation in the liver of bromobenzene-poisoned mice [15].
• Kinetic studies using reaction calorimetry were carried out under synthetically relevant conditions to study the mechanism of the amination of bromobenzene with primary and secondary amines using Pd(2)(dba)(3)/BINAP mixtures as well as preformed (dba)Pd(BINAP), (p-tolyl)(Br)Pd(BINAP), and Pd(BINAP)(2) complexes [16].
• Pharmacokinetics of DOX after BRB pretreatment was mildly changed from control [17].
• With the fluoro-, chloro-, and bromobenzene substrates, the values for the migration and retention of deuterium during hydroxylation (NIH shift) were nearly identical when the deuterium was either at the site of hydroxylation or at an adjacent site, indicating a possible common intermediate [18].
• Metabolic activation and detoxification of bromobenzene leading to cytotoxicity [19].

Anatomical context of bromobenzene

• Cell-free synthesis of heme oxygenase was performed in a rabbit reticulocyte lysate system using polysomes isolated from livers of rats treated with either hemin, Cd2+, or bromobenzene, and it was found that translatable mRNA specific for heme oxygenase was actually increased in the liver of rats treated with any of those inducers [20].
• To identify protein targets for bromobenzene metabolites in cytosol, we incubated liver microsomes and glutathione-depleted liver cytosol from phenobarbital-treated rats with [(14)C]bromobenzene in vitro [21].
• Identification of three protein targets for reactive metabolites of bromobenzene in rat liver cytosol [21].
• Identification of seven proteins in the endoplasmic reticulum as targets for reactive metabolites of bromobenzene [22].
• The membrane potential of liver mitochondria isolated from bromobenzene treated mice was studied [23].

Associations of bromobenzene with other chemical compounds

• Liver cell regeneration after selective zonal injury induced by bromobenzene (acinar zone III damage) and allyl alcohol (acinar zone I damage) was examined in the context of the simple liver acinus [24].
• Glutathione depletion and lipid peroxidation are therefore general phenomena occurring not only in the liver but in all the tissues as a consequence of bromobenzene poisoning [1].
• Bromobenzene metabolites have been determined in incubations of hepatocytes isolated from untreated, phenobarbital-treated, and beta-naphthoflavone-treated rats [25].
• The rapid and extensive conjugation of the bromophenols by intact cells may restrict their role as precursors of 4-bromocatechol, while bromobenzene 3,4-dihydrodiol is well converted into 4-bromocatechol by hepatocytes [25].
• Trolox C, ascorbic acid or catalase significantly inhibited bromobenzene-induced enhancement of fluorescence intensity (p<0.05-0.001), as well as reduced auto-intracellular oxidation in untreated Hep G2 cells [26].

Gene context of bromobenzene

• Beta-N-acetylhexosaminidase in the urine, kidney and serum of bromobenzene-intoxicated mice [27].
• Cytochrome P-450 system dependent depression of delta-aminolevulinic acid dehydratase activity by bromobenzene in rats [28].
• Effects of vitamins E, C and catalase on bromobenzene- and hydrogen peroxide-induced intracellular oxidation and DNA single-strand breakage in Hep G2 cells [26].
• Gene induction confirmed involvement of glutathione-S-transferase isozymes and epoxide hydrolase in bromobenzene metabolism and identified many genes possibly relevant in bromobenzene toxicity [29].
• Identification of a rat liver microsomal esterase as a target protein for bromobenzene metabolites [30].

Analytical, diagnostic and therapeutic context of bromobenzene

• Animals received one intraperitoneal injection of bromobenzene and were killed in groups of five at 1, 2, 3, 4, 7, and 14 days [6].
• The Mr 30,400 form was the main component of two isoelectric focusing bands with pI = 6.23 and 5.91, and the relative amounts of these net-charge variants was severely decreased in the kidneys of bromobenzene-treated rats [31].
• Specifically, the efficiency of the energy-transducing mitochondrial membrane was measured during the phase between the occurrence of a massive loss of hepatic GSH, after 2-3 hr of bromobenzene intoxication, and the appearance of lipid peroxidation and cell death (12-15 hr after treatment) [23].
• We then applied this system to the in vivo samples and successfully observed the increase in aldehydes in the liver of mice intraperitoneally injected with bromobenzene, an experimental animal model for lipid peroxidation [32].
• Bromobenzene-induced protein degradation was suggested from two-dimensional gel electrophoresis, upregulated mRNA levels for proteasome subunits and lysosomal cathepsin L, whereas also genes were upregulated with a role in protein synthesis [29].

References