Effects of phthalic acid esters on testicular mitochondrial functions in the rat.
Although it is well established that high dose administration of di(2-ethylhexyl) phthalate (DEHP) and its monoester metabolite (MEHP) induces severe testicular atrophy in rats, the mechanisms of this testicular injury is not clear. The present experiment was undertaken to examine the effects of DEHP and MEHP on mitochondrial functions of rat testis. DEHP and di-n-octyl phthalate (DOP), a DEHP isomer which causes less severe testicular injury, did not inhibit the state 3 oxygen consumption up to 0.65 mumole/ml in vitro. On the other hand, MEHP and mono-n-octyl phthalate (MOP), a metabolite of DOP, inhibited the state 3 oxygen consumption down to a concentration of 0.065 mumole/ml. Testicular mitochondrial respiratory functions of rats administered 2 g/kg DEHP were lower than those of control or DOP-treated rats. These differences were verified by characteristics of pharmacokinetic parameters and testicular concentrations of MEHP and MOP. It may be suggested that a possible mechanism of testicular atrophy induced by DEHP may be due to direct inhibition by MEHP (and partially DEHP) of the respiratory functions of Sertoli cell mitochondria in rat testis.
Oishi
S
S
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
D000818:Animals; D004051:Diethylhexyl Phthalate / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity* / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010795:Phthalic Acids / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D007773:Lactates; D010795:Phthalic Acids; D011773:Pyruvates; C041260:mono-n-octyl phthalate; C010715:di-n-octyl phthalate; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate