Mechanism of phthalate-induced inhibition of hepatic mitochondrial β-oxidation
作者： Lloyd D. Winberg , Mostafa Z. Badr
DOI: 10.1016/0378-4274(94)03199-1
关键词: Metabolism 、 Ketogenesis 、 Biochemistry 、 Cellular respiration 、 Mitochondrial respiratory chain 、 Fatty acid metabolism 、 Respiratory chain 、 Internal medicine 、 Phthalate 、 Endocrinology 、 Biology 、 Mitochondrion
摘要: Abstract Studies show that peroxisome proliferators inhibit mitochondrial β-oxidation of fatty acids. However, mechanism(s) this inhibitory effect has not been identified. This study was undertaken to delineate such mechanism(s). Ketogenesis significantly diminished in perfused livers from rats pre-treated with diethylhexyl phthalate (DEHP) compared control rats. Monoethylhexyl (MEHP; 200 μM), a primary metabolite DEHP and known proliferator, inhibited the oxidation palmitic acid as well its acyl-CoA acylcarnitine derivatives isolated mitochondria by about 50–60%. Similar concentrations MEHP also respiration succinate malate plus glutamate. ascorbate influenced MEHP. Considering assembly respiratory chain, these data indicate phthalates metabolism result inhibiting chain at level cytochrome c reductase. may represent an early step mechanism which cause hepatic proxisome proliferation.
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