Research progress in developmental toxicity and mechanism of letrozole in juvenile animals
10.3867/j.issn.1000-3002.2023.12.009
- VernacularTitle:来曲唑对幼年动物的发育毒性及机制研究进展
- Author:
Lili FU
1
,
2
,
3
;
Liping WEI
;
Chuqiao LIU
;
Qiaoyu TAO
;
Peng ZHANG
;
Yunliang QIU
Author Information
1. 安徽中医药大学药学院,安徽合肥 230012
2. 益诺思生物技术南通有限公司,江苏南通 226000
3. 南通市海门长三角药物高等研究院,江苏南通 226133
- Keywords:
letrozole;
aromatase inhibitors;
juvenile animal;
developmental toxicity
- From:
Chinese Journal of Pharmacology and Toxicology
2023;37(12):959-965
- CountryChina
- Language:Chinese
-
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.
