Disease relevance of Muconic aldehyde

• The results are discussed in terms of the toxicity of muconaldehyde at tissues distal from the liver, where it is believed to be formed from the metabolism of benzene [1].

High impact information on Muconic aldehyde

• Formation of muconaldehyde, an open-ring metabolite of benzene, in mouse liver microsomes: an additional pathway for toxic metabolites [2].
• Western blot analysis showed that the protein levels of c-jun increased in HL-60 cells treated with 1 microM muconaldehyde and cultured for 4-6 h and subsequently decreased gradually [3].
• Exposure of HL-60 cells to muconaldehyde resulted in an increase in c-fos and c-jun mRNA levels [3].
• The latter was highest in nuclear extracts from HL-60 cells treated with 1.0 microM muconaldehyde and cultured for 4 h [3].
• Increased gene expression in human promyeloid leukemia cells exposed to trans,trans-muconaldehyde, a hematotoxic benzene metabolite [3].

Chemical compound and disease context of Muconic aldehyde

• The toxicity of benzene, a human leukemogen and ubiquitous environmental pollutant, is mediated in part by ring-hydroxylated metabolites including hydroquinone (HQ) and ring-opened metabolites including trans,trans-muconaldehyde (muconaldehyde, MUC), and their interactions [4].

Biological context of Muconic aldehyde

• Using the 59Fe uptake method of Lee et al. it was shown that erythropoiesis in female mice was inhibited following IP administration of benzene, hydroquinone, p-benzoquinone, and muconaldehyde [5].
• The LD50 of trans,trans-muconaldehyde was 6.7 and 7.1 mg/kg body wt when calculated by two different methods [6].
• Administration of trans,trans-muconaldehyde (2 mg/kg, ip) daily for 10 and 16 days resulted in a statistically significant decrease in red blood cell count, hematocrit, hemoglobin, bone marrow cellularity, and hepatic total and free sulfhydryl content [6].
• Trans,trans-muconic acid (t,t-MA) is a biomarker of benzene exposure reflecting metabolic activation to trans,trans-muconaldehyde. t,t-MA background urinary levels are highly variable, thus limiting its use to exposure monitoring of levels over 1 ppm of benzene [7].
• The concentration at which 50% inhibition (IC50) was observed was 21 microM for acrolein, 23 microM for trans,trans-muconaldehyde, 27 microM for trans-4-hydroxynonenal and 330 microM for crotonaldehyde [8].

Anatomical context of Muconic aldehyde

• Our laboratory has shown that trans,trans-muconaldehyde (a possible metabolite of benzene) as well as acrolein and crotonaldehyde, when added to hepatic microsomes, decreased cytochrome P-450 (measured spectrophotometrically) [9].
• DNA-protein cross-link levels in bone marrow cells of mice treated with benzene or trans,trans-muconaldehyde [10].
• Pathways of trans,trans-muconaldehyde metabolism in mouse liver cytosol: reversibility of monoreductive metabolism and formation of end products [11].
• A metabolite of benzene, trans,trans-muconaldehyde (MUC) was found to be a strong inhibitor of gap junction intercellular communication (GJIC) with potency similar to that of chlordane [12].

Associations of Muconic aldehyde with other chemical compounds

• The presence of different metabolites of BZ such as hydroquinone, catechol, trans-trans muconic acid (MA, the oxidized form of trans-trans muconaldehyde, ttM), and total and conjugated phenol was evaluated in the urine of the exposed mice using HPLC [13].
• Mice liver microsomes oxidatively open the benzene ring to form trans,trans-muconaldehyde, a hematotoxic unsaturated aldehyde [14].
• The HPLC and radioactivity profiles of the muconaldehyde/deoxyguanosine reaction mixture indicated the presence of multiple adducts [14].
• The inhibition of muconaldehyde metabolism by microsomes in the presence of pyrazole indicates that there is cytosolic alcohol dehydrogenase (ADH) activity in the microsomes [15].
• A reversed-phase HPLC method is described for the separation and analysis of the thiobarbituric acid (TBA) adducts of the reactive aldehydes muconaldehyde (MUC) and malonaldehyde (MDA) [16].

Gene context of Muconic aldehyde

• Metabolism by contaminating ADH of muconaldehyde formed during microsomal incubation of benzene could be involved in the formation of CHO-M-OH and COOH-M-OH [15].
• Our laboratory recently identified trans,trans-muconaldehyde (MUC), a six-carbon diene dialdehyde, as a hematotoxic microsomal metabolite of benzene (Latriano et al., Proc Natl Acad Sci USA 83: 8356-8360, 1986) [17].
• Muconaldehyde-reacted BSA exhibits a decrease in amino groups as measured by the fluorescamine assay [18].
• Other fractions were found to contain muconaldehyde reductase activity independent of Adh1, and one enzyme was identified as the NADPH-dependent aldehyde reductase AKR1A4 [19].

Analytical, diagnostic and therapeutic context of Muconic aldehyde

• Separation of muconaldehyde, both with and without trapping with TBA, from other benzene metabolites in the incubation mixture was accomplished by HPLC [2].
• Gel filtration chromatography on Sephadex G-200 of muconaldehyde-reacted BSA shows elution of a high-molecular-weight fraction and a second fraction which elutes at the elution volume of monomeric unreacted BSA [18].

References