中国药理学与毒理学杂志2023，Vol.37Issue(12)：959-965,7.DOI:10.3867/j.issn.1000-3002.2023.12.009
来曲唑对幼年动物的发育毒性及机制研究进展
Research progress in developmental toxicity and mechanism of letrozole in juvenile animals
摘要
Abstract
Letrozole,a third generation non-steroidal aromatase inhibitor,has been approved for the treatment of breast cancer in women.In recent years,it has been used in the field of growth and development in children,such as childhood dwarfism,somatic delayed pubertal growth and precocious puberty,but the long-term effects on liver and kidney function,lipid metabolism,reproductive function and bone metabolism are unclear.Studies have shown that letrozole can cause abnormal testicular morphology,changes in seminiferous tubules and interstitial tissues,reduce bone density,affect the bal-ance of bone metabolism,and cause cognitive impairment and apoptosis of nerve cells.The mecha-nism of reproductive toxicity of letrozole may be related to its influence on the development and matura-tion of testicular cells,the expression of sex hormones and gonadotropins in vivo,and the distribution and expression of estrogen receptors in testicular tissues.The mechanism of bone metabolic toxicity is related to its increase in the proliferation and differentiation of osteoclasts induced by receptor activator of NF-κB ligand,as well as the increase of apoptosis,oxidative stress and NF-κB activity of osteo-blasts.The mechanism of cognitive toxicity is related to its regulation of classical and nonclassical effects of the hippocampus,reduction of glutamate uptake by astrocytes,and reduction of L-type calcium channel blockade of caspase 3 activation.This article is to provide reference for safe and effective use of letrozole in clinical pediatrics.关键词
来曲唑/芳香化酶抑制剂/幼年动物/发育毒性Key words
letrozole/aromatase inhibitors/juvenile animal/developmental toxicity分类
医药卫生引用本文复制引用
付莉莉,魏丽萍,刘楚乔,陶巧玉,张鹏,邱云良..来曲唑对幼年动物的发育毒性及机制研究进展[J].中国药理学与毒理学杂志,2023,37(12):959-965,7.基金项目
江苏省新药一站式高效非临床评价公共服务平台建设(BM2021002) Construction of a One-Step Efficient Non-clinical Evaluation Public Service Platform for New Drugs in Jiangsu Province(BM2021002) （BM2021002）
