Disease relevance of Crotonic aldehyde

• At the 0.6 mM dose, crotonaldehyde induced neoplastic lesions of the liver in 9 of 27 rats; 2 rats had hepatocellular carcinomas, and 9 rats had neoplastic nodules [1].
• These compounds are mutagenic in Salmonella, and crotonaldehyde is tumorigenic in rats [2].
• Formation of adducts in vitro may thus result from the reaction of hemoglobin with these impurities or with acetaldehyde condensation products (aldol) or from acetaldehyde condensation/dehydration products (crotonaldehyde) [3].
• Oxidative bioactivation of crotyl alcohol to the toxic endogenous aldehyde crotonaldehyde: association of protein carbonylation with toxicity in mouse hepatocytes [4].
• Through use of an initial fixative employing a combination of crotonaldehyde and glutaraldehyde, septa were preserved in thin sections of dividing cells of strains of Pseudomonas aeruginosa, Salmonella typhimurium, Shigella sonnei, and Escherichia coli when grown at 30 C in a dilute basal medium [5].

High impact information on Crotonic aldehyde

• Highly DNA-reactive alpha,beta-unsaturated aldehydes such as acrolein and crotonaldehyde are common environmental pollutants present in cigarette smoke and automobile exhaust and are also released endogenously by lipid peroxidation [6].
• The tumorigenic activities in F344 rats of crotonaldehyde, a representative alpha, beta-unsaturated carbonyl compound, and N-nitrosopyrrolidine, which could produce crotonaldehyde upon metabolism, were compared [1].
• When treated with the carbonyl reagent 2,4-dinitrophenylhydrazine, the reactive fractions yielded derivatives, some of which were identified by mass spectrometry as hydrazones of nonenal, heptenal, pentenal, and crotonaldehyde [7].
• Pt on mesostructured CeO(2) nanoparticles embedded within ultrathin layers of highly structured SiO(2) binder shows highest activity reported with 80% selectivity for the chemoselective hydrogenation of crotonaldehyde [8].
• Among the volatile compounds identified in cigarette smoke extracts, only the alpha,beta-unsaturated aldehydes, acrolein (inhibitory concentration of 50% [IC50] = 3 micromol/L) and crotonaldehyde (IC50 = 6 micromol/L), exhibited significant inhibition of cytokine production [9].

Chemical compound and disease context of Crotonic aldehyde

• Inhibition of glutathione S-transferase activity in human melanoma cells by alpha,beta-unsaturated carbonyl derivatives. Effects of acrolein, cinnamaldehyde, citral, crotonaldehyde, curcumin, ethacrynic acid, and trans-2-hexenal [10].
• The highest toxicity was exhibited by crotonaldehyde, allyl alcohol and acrolein [11].

Biological context of Crotonic aldehyde

• Reduced glutathione inhibited protein carbonyl formation, whereas other plasma antioxidants, including ascorbate, were ineffective. alpha, beta-Unsaturated aldehydes (acrolein and crotonaldehyde) in cigarette smoke may react with protein -SH and -NH2 groups by a Michael addition reaction that results in a protein-bound aldehyde functional group [12].
• A spectrum of mutations induced by crotonaldehyde in shuttle vector plasmids propagated in human cells [13].
• These data suggest that the inhibitory effects of WSF, acrolein, and crotonaldehyde on PMNL chemotaxis are not due to their inhibition of adherence [14].
• In primary colon mucosa cells from rats and humans, hexenal and crotonaldehyde (0.4 mM, 30 min) induced DNA damage, detected by single cell microgel electrophoresis (comet assay) [15].
• Reaction of crotonaldehyde with DNA, followed by treatment with NaBH(3)CN and enzyme hydrolysis, resulted in the formation of N(2)-(3-hydroxybutyl)dG (10), identified by its UV, MS, and proton NMR [16].

Anatomical context of Crotonic aldehyde

• Several putative adducts were observed in DNAs isolated from acrolein- and crotonaldehyde-treated human fibroblasts [17].
• Detection of acrolein and crotonaldehyde DNA adducts in cultured human cells and canine peripheral blood lymphocytes by 32P-postlabeling and nucleotide chromatography [17].
• The in vitro effects of the water-soluble fraction of whole cigarette smoke (WSF) and two alpha, beta-unsaturated aldehydes of cigarette smoke (acrolein and crotonaldehyde) on polymorphonuclear leukocyte (PMNL) adherence were determined with nylon fiber columns [14].
• In Namalva cells DNA single strand breaks were induced by much lower concentrations of acrolein, crotonaldehyde and (E)-2-hexenal than in primary rat hepatocytes [18].
• Crotonaldehyde induced dose related increase in the percentage of abnormal sperm heads [19].

Associations of Crotonic aldehyde with other chemical compounds

• The repair of acetaldehyde/crotonaldehyde-induced guanine (N(2))-guanine (N(2)) interstrand cross-links (ICLs), 3-(2-deoxyribos-1-yl)-5,6,7,8-(N(2)-deoxyguanosyl)-6(R or S)-methylpyrimido[1,2-alpha]purine-10(3H)-one, was studied using a shuttle plasmid bearing a site-specific ICL [20].
• Formation of cyclic deoxyguanosine adducts in Chinese hamster ovary cells by acrolein and crotonaldehyde [2].
• Cyclic 1,N2-propanodeoxyguanosine adducts are formed in vitro in DNA treated with alpha-acetoxy-N-nitrosopyrrolidine or its metabolite, crotonaldehyde [21].
• The results showed that butadiene monoxide and crotonaldehyde formation was optimal at pH 6 [22].
• 4-Hydroxy-2-nonenal (HNE) and crotonaldehyde (CA) are alpha,beta-unsaturated aldehydes (enals) produced by lipid peroxidation [23].

Gene context of Crotonic aldehyde

• The rate of Acr adduct formation was about 5-10-fold that of Cro adducts, depending on the type of PUFAs, and the rate of formation of HNE adducts from AA was also considerably slower than that of Acr adducts [24].
• The hepatocarcinogen NPYR is metabolically activated by alpha-hydroxylation mediated by cytochrome P-450 enzymes to yield a 4-oxobutylating agent and 2-butenal (crotonaldehyde) [25].
• The apparent Km value for Thermococcus strain ES-1 ferredoxin was 10 microM (with crotonaldehyde as the substrate) [26].
• In the present study we have evaluated whether or not exposure to crotonaldehyde results in a significant increase in the frequency of abnormal sperm heads in male Swiss albino mice [19].
• Unsaturated aldehydes, 4-hydroxynonenal, crotonaldehyde and acrolein, given by the same route induced putatively preneoplastic single cells positive for GST-P [27].

Analytical, diagnostic and therapeutic context of Crotonic aldehyde

• Using a sensitive 32P-postlabeling method combined with high performance liquid chromatography, we obtained evidence that 1,N2-propanodeoxyguanosine adducts of acrolein (AdG) and crotonaldehyde (CdG) are present in the liver DNA of humans and rodents without carcinogen treatment [28].
• In order to develop an immunoassay for DNA modifications resulting from exposure to crotonaldehyde, monoclonal antibodies specific for the 8R,6R- and 8S,6S-stereoisomers of 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxy-6 - methylpyrimido[1,2-a]purine-10(3H)one were produced [29].
• Spontaneous cyclization gave the two diastereomers of the crotonaldehyde-adducted nucleoside that were readily separated by HPLC [30].
• Adult male mice were treated with 8, 16 and 32 microl/kg b.w. of crotonaldehyde as a single intraperitoneal injection [19].
• Among the three compounds, crotonaldehyde caused the highest activity induction (9.2-fold), but Western blot expression was the highest only for CmGSTU3 [31].

References