Diethylmaleate

Diethylmaleate (DEM) is a maleic acid diethyl ester.

DEM is used in many organic syntheses as an additive and intermediate for pigments, plastics, pharmaceuticals, as well as agricultural products. DEM is also an intermediate for the production of adhesives, paints, and copolymers.

In vitro: Previous study found that the GSH depletion by DEM could inhibit the growth of transformed cells. The non-cytotoxic dose of DEM led to GSH depletion, cell cycle arrest, ROS generation, decrease in anchorage independent growth, apoptosis, gene expression changes as well as the activation of all three MAPK family members. In addition, the increased intracellular GSH levels by GSHe opposited the effect of DEM [1].

In vivo: Animal study was conducted to evaluate the effect of DEM induced oxidative stress on male fertility in mice. Results showed that the i.p. injection of DEM for two weeks led to decrease in reduced glutathione and increase in the oxidized glutathione levels in the testis. Moreover, the motility and concentration of sperm were found to be reduced significantly with a obvioius reduction in the litter size. It was also found that expression of redox sensitive transcription factor, cjun and cfos genes, gamma-glutamyl cysteine synthetase and manganese superoxide dismutase expression were affected after DEM treatment, as demonstrated by RT-PCR data. Additionally, the enzyme activity of SOD also increased by the treatment of DEM [2].

Clinical trial: Up to now, there is no clinical data reported for diethyl maleate.

References:
[1] Priya S,Nigam A,Bajpai P,Kumar S.  Diethyl maleate inhibits MCA+TPA transformed cell growth via modulation of GSH, MAPK, and cancer pathways. Chem Biol Interact.2014 Aug 5;219:37-47.
[2] Kaur P,Kalia S,Bansal MP.  Effect of diethyl maleate induced oxidative stress on male reproductive activity in mice: redox active enzymes and transcription factors expression. Mol Cell Biochem.2006 Oct;291(1-2):55-61.