maxacalcitol and Inflammation

In general, chronotherapy is desirable for a more effective and/or safe dosage regimen. In this study, a daily rhythm of skin vitamin D receptor (VDR) and chronotherapeutic profiles of maxacalcitol, a vitamin D analogue, were evaluated using mice with skin inflammation induced by topical 12-O-tetradecanoylphorbol-13-acetate (TPA). This study showed that skin nuclear VDR expression in TPA-treated mice has a daily rhythm with the peak at the middle of active period. The effects of maxacalcitol were greater after dosing during early to middle of active period than those after dosing during early to middle of inactive period. These data suggest that chronotherapeutic profiles of maxacalcitol partly depend on the daily rhythm of skin nuclear VDR in TPA-treated mice. Because TPA-treated mice are considered as one of animal models of psoriasis, these animal data might be helpful for establishing chronotherapeutic approach of maxacalcitol in clinical practice.

Topics: Animals; Calcitriol; Chronotherapy; Circadian Rhythm; Inflammation; Male; Mice; Mice, Inbred C57BL; Psoriasis; Receptors, Calcitriol; Skin; Tetradecanoylphorbol Acetate

The anti-inflammatory effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3 [22-oxa-1 alpha,25(OH)2D3], an analogue of the active form of vitamin D3, was studied regarding carrageenin-induced inflammation in rats. In the early phase of the inflammation, the formation of granulation tissue and the weight of exudate were significantly suppressed by both oral and local administrations of 22-oxa-1 alpha,25(OH)2D3 daily for 4 d (day 0-3) after carrageenin injection, though the local injection of 22-oxa-1 alpha,25(OH)2D3 (7 and 10 micrograms/kg) into the carrageenin-air-pouch was much more effective than the oral administration of the compound (20 micrograms/kg). Similarly, oral and local administrations of 22-oxa-1 alpha,25(OH)2D3 from day 4 to 7 significantly suppressed the increase in exudate and the proliferation of granulation tissue in the late phase of carrageenin-induced inflammation in rats. The results suggest that 22-oxa-1 alpha,25(OH)2D3 has an anti-inflammatory activity on both the acute and proliferative phases of inflammation in rats.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Calcitriol; Carrageenan; Exudates and Transudates; Granulation Tissue; Inflammation; Male; Rats; Rats, Wistar