Chelation therapy in aluminum-loaded rats: influence of age

The influence of age at which aluminum (Al) exposure was initiated on the e fficacy of chelation therapy in mobilizing Al was investigated in two group s of male rats exposed to this element at two different stages of the life cycle. Young (21 days old) and old (18 months) rats were exposed to 0 and 5 0 mg Al/kg/day administered as Al nitrate in drinking water for a prelimina ry period of 14 days followed by a period of 100 days, in which A-exposed a nimals received 100 mg Al/kg/day. At the end of the period of exposure, A-l oaded rats in each age group were given one of the following treatments: s. c. deferoxamine (DFO), oral 1,2-dimethyl-3-hydroxypyrid-4-one (L1) and 1-(p -methylbenzyl)-2-ethyl-3-hydroxypyrid-4-one (MeBzEM) at doses of 0.89 mmol/ kg/day for 5 consecutive days. Another group of Al-exposed rats received a concurrent administration of s.c. DFO and oral L1 both at 0.45 mmol/kg/day. During chelation therapy urines were collected daily. Control groups inclu ded rats exposed and unexposed to Al. Oral administration of L1 was the mos t effective treatment in enhancing urinary Al excretion in both age groups of Al-loaded rats. This beneficial effect was similar for old and young ani mals. Concurrent administration of DFO and L1 had no advantages over the us e of either single agent, while MeBzEM was not effective in mobilizing Al f rom Al-exposed rats. (C) 1999 Elsevier Science Ireland Ltd. All rights rese rved.