Yokel R A
College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Fundam Appl Toxicol. 1987 Nov;9(4):795-806. doi: 10.1016/0272-0590(87)90186-2.
To assess aluminum toxicity to the neonatal and immature rabbit, rabbits received 20 sc Al lactate injections of 0 or 400 mumol Al/kg during the first month postpartum or 0, 25, 100, or 400 mumol Al/kg during the second month postpartum. Results were compared to studies in which pregnant, lactating, or adult rabbits received comparable Al injections. Aluminum injections to neonatal rabbits decreased milk consumption, but not as severely as seen in neonatal rabbits of does receiving Al during gestation or lactation. Reduction in body weight gain was greater in adult rabbits than in any group of rabbits exposed to Al at a younger age. Increased carpal joint width, suggestive of poor bone calcification, was observed in rabbits receiving 400 mumol Al injections during the second postnatal month, but not in any other Al-exposed group. Tissue Al accumulation, particularly in reticuloendothelial organs, the kidney and skeletal system, seems to be most pronounced in adult rabbits. Clearance of Al from these tissues is extremely slow. Learning and memory changes were not observed after Al treatment of neonatal and immature rabbits, compared to the biphasic effect (enhancement after low doses, attenuation after high doses) seen in gestationally exposed rabbits and the attenuation observed in adult rabbits. Taken together, these results demonstrate prolonged effects of reduced body weight, impairment of bone formation, and tissue Al accumulation following Al exposure that are not readily reversed with termination of exposure. The results show that the immature rabbit is most susceptible to Al-induced skeletal toxicity and the mature rabbit most susceptible to Al-induced behavioral toxicity.
为评估铝对新生和未成熟兔的毒性,在产后第一个月,兔接受20次皮下注射乳酸铝,剂量分别为0或400 μmol铝/千克;或在产后第二个月接受剂量为0、25、100或400 μmol铝/千克的乳酸铝皮下注射。将结果与怀孕、哺乳或成年兔接受类似铝注射的研究进行比较。给新生兔注射铝会减少其奶摄入量,但不如妊娠或哺乳期接受铝注射的母兔所生新生兔减少得那么严重。成年兔体重增加的减少幅度大于任何一组在较幼年时接触铝的兔。在出生后第二个月接受400 μmol铝注射的兔中观察到腕关节宽度增加,提示骨钙化不良,但在任何其他铝暴露组中未观察到。组织铝蓄积,特别是在网状内皮器官、肾脏和骨骼系统中,似乎在成年兔中最为明显。铝从这些组织中的清除极其缓慢。与在妊娠暴露兔中看到的双相效应(低剂量时增强,高剂量时减弱)以及在成年兔中观察到的减弱相比,对新生和未成熟兔进行铝处理后未观察到学习和记忆变化。综上所述,这些结果表明,铝暴露后体重减轻、骨形成受损和组织铝蓄积的影响持续存在,暴露终止后不易逆转。结果表明,未成熟兔对铝诱导的骨骼毒性最敏感,成熟兔对铝诱导的行为毒性最敏感。