A comparison between 1,25-dihydroxy-22-oxavitamin D3 and 1,25-dihydroxyvitamin D3 regarding suppression of parathyroid hormone secretion and calcaemic action
| Autor: | Michinori Hirata, Fumihiko Ichikawa, Kyoko S. Katsumata, Masafumi Fukagawa, Noboru Kubodera, Koichi Endo |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Hypercalcaemia Parathyroid hormone Nephrectomy Rats Sprague-Dawley chemistry.chemical_compound Calcitriol Internal medicine medicine Vitamin D and neurology Animals Uremia Transplantation Hyperparathyroidism business.industry Body Weight Alfacalcidol medicine.disease Rats Endocrinology chemistry Parathyroid Hormone Nephrology Kidney Failure Chronic Parathyroid hormone secretion Calcium Secondary hyperparathyroidism business |
| Zdroj: | Nephrology Dialysis Transplantation. 17:41-45 |
| ISSN: | 1460-2385 0931-0509 |
| Popis: | Background. Since Slatopolsky et al. (J Clin Invest 1984; 74: 2136-2143) reported the effect of active vitamin D, 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), on secondary hyperparathyroidism (2HPT) which accompanies chronic renal failure, there have been several studies of the therapeutic effects of 1,25(OH) 2 D 3 in this disease. Although parathyroid hormone (PTH) is suppressed by treatment with 1,25(OH) 2 D 3 , long-term treatment with 1,25(OH) 2 D 3 tends to induce hypercalcaemia. Therefore, an analogue of 1,25(OH) 2 D 3 , 1,25-dihydroxy-22-oxavitamin D 3 (22-oxacalcitriol, OCT) with less calcaemic activity, was developed for the treatment of 2HPT. Methods. In order to clarify the differences between the effects of 1,25(OH) 2 D 3 and OCT on 2HPT associated with chronic renal failure, these compounds were administered by intermittent i.v. injection for 2 weeks in rats with mild to moderate uraemia. Results. 1,25(OH) 2 D 3 markedly suppressed PTH levels, but increased serum calcium (Ca). OCT also markedly suppressed PTH levels, but induced only a slight increase in serum Ca. 1,25(OH) 2 D 3 caused a dose-dependent decrease in body weight, whereas OCT had no effect on body weight in uraemic rats. Based on those doses of OCT and 1,25(OH) 2 D 3 , which resulted in a 60% suppression of PTH, and induced hypercalcaemia, we consider the relative ratios for efficacy and Ca-elevating activity between OCT and 1,25(OH) 2 D 3 to be 1: 8 and 1: 48, respectively. Conclusions. OCT suppressed PTH levels with a slight increase in serum Ca without changing the body weight in uraemic rats. This observation suggests that OCT might be a useful vitamin D analogue for 2HPT management in long-term clinical treatment. |
| Databáze: | OpenAIRE |
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