Methoxyacetic acid and ethoxyacetic acid inhibit mitochondrial function in vitro.
Ethylene glycol monomethyl ether (EGME) and ethylene glycol monoethyl ether (EGEE) have recently been shown to be potent reproductive toxicants in laboratory animals. The toxicity of these compounds is believed to be due to their metabolites, methoxyacetic acid (MAA) and ethoxyacetic acid (EAA). Since the primary targets of EGME and EGEE appear to be tissues with rapidly dividing cell systems and high rates of respiration and energy metabolism, the effects of these compounds and their proposed metabolites on mitochondria were investigated. At concentrations beginning at 3.85 mM, MAA and EAA inhibited state 3 respiration and the respiratory control ratio (RCR) in hepatic mitochondria with either succinate or citrate/malate as substrates. Cytochrome c oxidase activity was also inhibited by both metabolites at similar concentrations. The effects of MAA, the metabolite from the more potent compound, on testicular mitochondria were found to be comparable. Neither EGME or EGEE appeared to affect mitochondrial function at concentrations as high as 238 or 113 mM, respectively. These results support the hypothesis that the toxicity of EGME and EGEE are due to their metabolites, MAA and EAA, and that these metabolites may exert their effects, in part, on mitochondrial function.
Beattie
P J
PJ
Department of Environmental and Industrial Health, University of Michigan, Ann Arbor 48109-2029.
Brabec
M J
MJ
D000085:Acetates / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D005026:Ethylene Glycols / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D000085:Acetates; D005026:Ethylene Glycols; C034096:ethoxyacetic acid; C005219:methyl cellosolve; C013598:methoxyacetic acid; C021296:2-ethoxyethanol