title: Ethylene glycol ethers induce apoptosis and disturb glucose metabolism in the rat brain.
abstract: BACKGROUND
  Ethylene glycol ethers (EGEs) are compounds widely used in industry and household products, but their potential, adverse effect on brain is poorly understood, so far. The aim of the present study was to determine whether 4-week administration of 2-buthoxyethanol (BE), 2-phenoxyethanol (PHE), and 2-ethoxyethanol (EE) induces apoptotic process in the rat hippocampus and frontal cortex, and whether their adverse effect on the brain cells can result from disturbances in the glucose metabolism.
  
  
  METHODS
  Experiments were conducted on 40 rats, exposed to BE, PHE, EE, saline or sunflower oil for 4 weeks. Markers of apoptosis and glucose metabolism were determined in frontal cortex and hippocampus by western blot, ELISA, and fluorescent-based assays.
  
  
  RESULTS
  BE and PHE, but not EE, increased expression of the active form of caspase-3 in the examined brain regions. BE and PHE increased caspase-9 level in the cortex and PHE also in the hippocampus. BE and PHE increased the level of pro-apoptotic proteins (Bax, Bak) and/or reduced the concentration of anti-apoptotic proteins (Bcl-2, Bcl-xL); whereas, the effect of BE was observed mainly in the cortex and that of PHE in the hippocampus. It has also been found that PHE increased brain glucose level, and both BE and PHE elevated pyruvate and lactate concentration.
  
  
  CONCLUSIONS
  It can be concluded that chronic treatment with BE and PHE induced mitochondrial pathway of apoptosis, and disturbed glucose metabolism in the rat brain.
authors.affiliation: Department of Biochemical Toxicology, Medical College, Jagiellonian University, Kraków, Poland. Electronic address: bartosz.pomierny@uj.edu.pl.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pomierny
authors.affiliation: Department of Biochemical Toxicology, Medical College, Jagiellonian University, Kraków, Poland. Electronic address: weronika.krzyzanowska@uj.edu.pl.
authors.forename: Weronika
authors.initials: W
authors.lastname: Krzyżanowska
authors.affiliation: Department of Toxicology, Chair of Toxicology, Faculty of Pharmacy, Medical College, Jagiellonian University, Kraków, Poland. Electronic address: ewa.niedzielska@uj.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Niedzielska
authors.affiliation: Department of Biochemical Toxicology, Medical College, Jagiellonian University, Kraków, Poland. Electronic address: zaneta.broniowska@uj.edu.pl.
authors.forename: Żaneta
authors.initials: Ż
authors.lastname: Broniowska
authors.affiliation: Department of Biochemical Toxicology, Medical College, Jagiellonian University, Kraków, Poland; Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: boguslawa.budziszewska@uj.edu.pl.
authors.forename: Bogusława
authors.initials: B
authors.lastname: Budziszewska
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004987:Ethers / Q000633:toxicity; D005026:Ethylene Glycols / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004987:Ethers; D005026:Ethylene Glycols; C005398:phenoxyethanol; C017096:n-butoxyethanol; C021296:2-ethoxyethanol; D005947:Glucose
keywords: Apoptosis; Environmental toxins; Ethylene glycol ethers; Glucose metabolism