124521-13-7Relevant articles and documents
Formation of a vitamin C conjugate of acrolein and its paraoxonase-mediated conversion into 5,6,7,8-tetrahydroxy-4-oxooctanal
Kesinger, Nicholas G.,Langsdorf, Brandi L.,Yokochi, Alexandre F.,Miranda, Cristobal L.,Stevens, Jan F.
, p. 836 - 844 (2010)
Vitamin C (ascorbic acid) has been reported to participate in Michael addition reactions in vitro to form vitamin C conjugates with α,β-unsaturated aldehydes, such as acrolein. This study shows evidence for the formation and metabolism of the vitamin C conjugate of acrolein (AscACR) in cultured human monocytic THP-1 cells exposed to acrolein diacetate. By using 18O and 13C labeling in combination with liquid chromatography-tandem mass spectrometry, AscACR was shown to undergo hydrolytic conversion of the ascorbyl lactone into an intermediate carboxylic acid. Subsequent decarboxylation of the carboxylic acid yielded 5,6,7,8-tetrahydroxy- 4-oxooctanal (THO). When THP-1 cells were pretreated with ascorbic acid (1 mM, 18 h) and then exposed to acrolein diacetate, THO was detected as its pentafluorobenzyl oxime derivative in the cell lysates and medium. Treatment of THP-1 cells with both ascorbic acid and acrolein diacetate was required for THO formation. The formation of THO from AscACR was facilitated by the lactonase enzymes, human recombinant paraoxonases 1 and 2. THP-1 cells exhibited PON activity, which explains the catalytic conversion of AscACR into THO in these cells. THO was formed in addition to metabolites of the glutathione conjugate of acrolein, indicating that THO formation contributes to the elimination of acrolein in a cellular environment.
The influence of glutathione and detoxifying enzymes on DNA damage induced by 2-alkenals in primary rat hepatocytes and human lymphoblastoid cells
Eisenbrand,Schuhmacher,Golzer
, p. 40 - 46 (2007/10/03)
The reaction of 2-alkenals with GSH to form GSH conjugates by Michael addition is a major detoxification pathway. The reaction proceeds at a much higher rate under catalysis by glutathione S-transferase (GST) than the non- enzymatic reaction. Oxidation of 2-alkenals to the corresponding acids by cytosolic and microsomal fraction of rat liver also contributes to detoxification. Primary rat hepatocytes rich in GSH and proficient for GST and other metabolizing enzymes consume much more alkenal than human lymphoblastoid cells (Namalva cells), that are poor in GSH and in metabolic activities. 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. In both cell systems intracellular GSH depletion by 2-alkenals proceeds in a dose dependent manner, approaching about 20% of pretreatment level before DNA damage becomes detectable. GSH conjugates of (E)-2-hexenal and (2E, 6Z)-2,6-nonadienal induce DNA damage in Namalva cells at high concentrations (1.5 mM). In the absence of GSH these conjugates decompose slowly into aldehyde and GSH. Although the rate of decomposition is only about 10-4 times that of Michael adduct formation, such GSH conjugates could potentially function as transport molecules for 2-alkenals, if they reach tissues low in GSH and GST.
