Effects of parathyroid hormone on plasma zinc concentration in rat with chronic renal failure.
Although both secondary hyperparathyroidism (HPT) and hypozincemia are commonly observed in humans and animals with chronic renal failure (CRF), the relationship between secondary HPT and hypozincemia is little delineated. The present study was designed to examine whether the elevated plasma parathyroid hormones (PTH) levels do affect the disposition of extrarenal zinc and decrease plasma zinc level in CRF rats. The experiment was performed in normal and CRF rats with intact parathyroid gland and parathyroidectomized (PTX), using an acute zinc load alone or in combination with PTH infusion in five groups of rats: normal control, CRF control, CRF + PTH, CRF + PTX and CRF + PTX + PTH. Five sixths nephrectomy was used to produce CRF. All rats were infused with 0.05 mg/kg/min ZnSO4 alone or in combination with 10 microg/kg/min PTH through intravenous infusion for 90 min with serial monitoring of plasma zinc levels every 30 min. The alteration of plasma interleukin-6 (IL-6) levels and the effect of zinc levels in red blood cells (RBCs), as well as the output of bile juice zinc and urinary zinc excretion during the 90-min infusion were also examined. After 90-min infusion, liver tissue was harvested to determine its contents of zinc and metallothionein (MT). During zinc sulfate infusion, the responses of plasma zinc concentration in PTH-combined infusion groups markedly decreased as compared with those of the non-PTH-combined infusion groups, especially in the CRF rats with PTX. However, when zinc sulfate alone was infused, the response of plasma zinc concentration was found to increase in CRF rats with PTX as compared with that of the CRF control rats. PTH infusion groups significantly increased the levels of plasma IL-6 (P < 0.05), but it did not alter the levels of RBC zinc and the secretion of bile zinc during the 90-min infusion. After 90-min zinc sulfate infusion, higher liver zinc and MT contents were found in CRF control, CRF + PTH and CRF + PTX + PTH rats, but were [corrected] not found in the CRF + PTX rats. Zinc sulfate infused alone was found to increase the excretion of basal zinc in bile juice and urine, in both normal and CRF rats. The percentage of zinc load translocated out from the plasma during 90-min zinc sulfate infusion significantly rises in CRF rats and CRF rats with PTH-combined infusion as compared with normal control rats. However, in CRF rats with PTX, the percentage of zinc load translocated out from plasma during 90-min zinc sulfate infusion was similar to that in the normal control rats. Therefore, we suggested that in CRF rats, the excessive secretion of PTH may play a role in the pathogenesis of hypozincemia because PTH enhanced extrarenal zinc disposal.
Chen
Shu-Ming
SM
Department of Medical Research and Education Nephrology Laboratory, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. smchen@vghtpe.gov.tw
Kuo
Cheng-Deng
CD
Liao
Jyh-Fei
JF
Ho
Low-Tone
LT
D000818:Animals; D001646:Bile / Q000378:metabolism; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D009994:Osmolar Concentration; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D016105:Parathyroidectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013965:Thyroidectomy; D015032:Zinc / Q000097:blood* / Q000378:metabolism / Q000652:urine; D019287:Zinc Sulfate / Q000008:administration & dosage / Q000494:pharmacology
D010281:Parathyroid Hormone; D019287:Zinc Sulfate; D015032:Zinc