Progress of carcinogenesis and possible mechanisms of peroxisome proliferator-activated receptor agonists
10.3867/j.issn.1000-3002.2014.03.025
- VernacularTitle:过氧化物酶体增殖物激活受体激动剂类药物的致癌性和致癌机制研究进展
- Author:
Liguo XING
;
Yingliang WU
- Publication Type:Journal Article
- Keywords:
peroxiso me proliferators activated receptors agonists;
toxic actions;
carcinogens
- From:
Chinese Journal of Pharmacology and Toxicology
2014;(3):455-461
- CountryChina
- Language:Chinese
-
Abstract:
Peroxisome proliferator-activated receptors (PPARs)are ligand-activated nuclear tran-scription factors,playing an important role in the regulation of glucose and lipids metabolism,inflamma-tion response,proliferation and differentiation.Some drugs targeted on PPARs,such as lipid-lowering and antidiabetic drugs have been developed.Some PPAR agonists were found carcinogenic in animal experi ments,including PPAR αagonist fibrates,PPARγagonist thiazolidinediones,PPARα/γdual ago-nist compounds,and PPARδagonist compounds for clinical development.PPARαagonist carcinogenicity is associated with PPAR receptor activation that regulates lipid metabolis m,and leads to lipids abnormali-ties and increase by peroxisome oxidase in reactive oxygen species (ROS),causing DNA damage. Kupffer cells can generate ROS by NAD PH oxidase that pro motes hepatocyte proliferation and inhibition of apoptosis.PPARγagonist carcinogenicity is generally caused by bladder stone.The carcinogenicity of PPAR agonists to humans has not been confirmed,but the carcinogenic potential of these drugs can-not be ignored.
