Hepatic levels of cadmium, zinc and copper in multiparous, nulliparous and ovariectomized mice fed either a nutrient-sufficient or -deficient diet containing cadmium.
As a simulation of etiological factors known for Itai-Itai disease, female mice were subjected to the individual and combined stresses of dietary cadmium, nutrient-deficient diet, multiparity and ovariectomy. From age 68 days, female mice were maintained on either nutrient-sufficient (+) or -deficient (-), purified diets containing either 0.25 (environmental), 5, or 50 ppm Cd as CdCl(2); the nutritional composition of (-) diet simulated that of food consumed by Japanese women who contracted Itai-Itai disease. At age 70 days, half of the mice began a breeding regimen of six consecutive, 42-day rounds of pregnancy/lactation (PL mice); the remainder were maintained as virgin, non-pregnant controls (NP mice). Limited numbers of PL and NP mice were sacrificed at the end of each reproductive round. PL(+) mice taken in a given round had successively borne litters in that round and all preceding ones. PL(-) females taken at the end of round (R)-1, -2 and -3 had successively borne litters through those rounds; those taken at the end of R-5 or -6 had nonsuccessively borne litters in four of five or three of six rounds, respectively. At the end of the 252-day reproductive period, remaining females entered the 392-day, post-reproductive phase of the experiment. At age 546 days (mid-R-12), PL females having successfully borne at least three litters were ovariectomized (OV) to mimic human menopause, while NP females were either ovariectomized or sham-operated (SO). After surgery, all females were maintained to age 714 days (mid-R-16), then sacrificed. Food consumption, monitored on a weekly basis over the first nine rounds, was in general not significantly affected by dietary Cd level or nutrient deficiencies for females of the same reproductive status; consumption was increased about 2.5-fold in PL versus NP groups during the reproductive period and about 1.4-fold during the post-reproductive period. Over the reproductive period, small increases in liver concentrations of Zn and Cu were observed (ca. 3.1- and 2.5-fold, respectively) with far larger increases for Cd (ca. 22200-fold). Threshold hepatic Cd concentrations below which the concentrations of Zn and Cu were relatively constant and independent of Cd concentration were identified; they were 2.7 microg Cd/g liver for Zn and 3.3 microg Cd/g liver for Cu for females consuming (+) diet, and 4.9 microg Cd/g liver for Zn and 4.5 microg Cd/g liver for Cu for females consuming (-) diet. Regardless of Cd exposure level, round-by-round hepatic concentrations of Cd were generally 2- to 6-fold higher in PL than NP mice, while Zn or Cu levels were generally only 1.1- to 2.5-fold higher. For each reproductive round, hepatic concentrations of Cd in NP females were consistently about 10-fold greater in mice exposed to 50 than 5 ppm dietary Cd: corresponding Zn levels were essentially equivalent. For PL females. Cd levels were about 7-fold greater in 50 than 5 ppm Cd-exposed groups, however Zn concentrations were about 45% decreased. The pattern of Cd, Zn and Cu sequestration established during the reproductive period clearly differed from that of the post-reproductive period. Between R-6 and -16, hepatic concentrations of Cd, Zn and Cu appreciably decreased (14-69%) in 5 ppm Cd-exposed NPOV and PLOV females regardless of diet-type consumed. At the 50 ppm Cd level, Cd and Zn concencentrations dramatically rose with increases in Cd (37-129%) exceeding those of Zn (12-21%).
Whelton
B D
BD
Department of Chemistry and Biochemistry, Eastern Washington University, Cheney 99004-2431, USA.
Peterson
D P
DP
Moretti
E S
ES
Mauser
R W
RW
Bhattacharyya
M H
MH
D000818:Animals; D002104:Cadmium / Q000032:analysis; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D002105:Cadmium Poisoning / Q000209:etiology*; D003300:Copper / Q000032:analysis; D004032:Diet; D004435:Eating / Q000187:drug effects; D005260:Female; D007668:Kidney / Q000737:chemistry; D007774:Lactation; D008099:Liver / Q000737:chemistry*; D019216:Metals, Heavy / Q000032:analysis*; D051379:Mice; D010052:Ovariectomy; D010298:Parity; D011247:Pregnancy; D015032:Zinc / Q000032:analysis
D019216:Metals, Heavy; D002104:Cadmium; D003300:Copper; D015032:Zinc; D019256:Cadmium Chloride