Influence of dietary zinc on di(2-ethylhexyl)phthalate-induced testicular atrophy and zinc depletion in adult rats.
Groups of 48 adult male F344 rats were maintained on synthetic diets containing 20 ppm (normal), 2 ppm (low), or 200 ppm (high) zinc. After 1 week of acclimation to the various diets, groups of 12 rats from each dietary regimen were gavaged for 13 consecutive days with 0.0 (vehicle), 0.33, 1.0, or 3.0 g/kg di(2-ethylhexyl)phthalate (DEHP). These were selected as relatively nontoxic, mildly toxic, and moderately toxic doses for producing testicular injury in adult male rats. At termination on the 14th day, body weight gain was reduced by 3.0 g/kg DEHP dose in the normal and low-zinc diet groups but not in the high-zinc diet group. The low-zinc diet alone reduced body weight gain, independent of DEHP treatment. DEHP had no perceptible effects on the weights of testis, seminal vesicle, prostate, or epididymis from rats maintained on normal- or high-zinc diets, but reduced the weights of all of these organs from animals on the low-zinc diet in a dose-dependent manner. Lactate dehydrogenase activity, total and free sulfhydryl contents, and zinc concentrations in testes were also reduced, and testicular degeneration was induced by DEHP in the low-zinc diet groups. In contrast, dose-dependent liver enlargement and hypolipidemia (reduction of serum cholesterol and triglyceride concentrations) were produced by equivalent doses of DEHP in all of the three zinc groups. The selectively enhanced susceptibility of adult male F344 rats on a zinc deficient diet to the gonadotoxic effects of DEHP supports the hypothesis that testicular zinc depletion is causally related to the ensuing testicular and accessory sex organ atrophies. Other biological effects of DEHP (e.g., hypolipidemia, hepatomegaly) appear to occur independent of zinc homeostasis.
D000818:Animals; D001284:Atrophy; D001835:Body Weight / Q000187:drug effects; D004051:Diethylhexyl Phthalate; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013438:Sulfhydryl Compounds / Q000032:analysis; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D015032:Zinc / Q000172:deficiency* / Q000494:pharmacology
D013438:Sulfhydryl Compounds; D004051:Diethylhexyl Phthalate; D007770:L-Lactate Dehydrogenase; D015032:Zinc