Chlorpromazine and Tiaprofenic Acid-induced p38 and Erk1/2 Expression Change in Three Phototoxicity Test Methods
10.13748/j.cnki.issn1007-7693.20233124
- VernacularTitle:氯丙嗪和噻洛芬酸在3种光毒性测试中致p38和Erk1/2表达变化研究
- Author:
Xiaoxing WU
1
;
Shuhuai CHEN
2
;
Yanjuan LIU
3
;
Jing SANG
2
Author Information
1. Center for Basic and Translational Research, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
2. Zhejiang Institute for Food and Drug Control, Hangzhou 310052, China
3. Collaboration Innovation Center of Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310032, China
- Publication Type:Journal Article
- Keywords:
phototoxicity ;p38;Erk1/2; artificial skin model
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(11):1491-1498
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To explore the intracellular expression changes of p38 and Erk1/2 under three phototoxic conditions, compare three detection methods, and further investigate their molecular mechanisms.
METHODS
The methods involved using three testing approaches to assess the phototoxicity of chlorpromazine(CPZ) and tiaprofenic acid(TA). Subsequently, whole-cell lysates from the biological samples used in the three testing methods were collected, and the changes in the expression levels of intracellular p38 and Erk1/2 were evaluated using Western blotting.
RESULTS
All three testing methods accurately identified CPZ and TA as phototoxic compounds. In the 3T3 NRU phototoxicity assay, compared to the control group, the expression of p38 significantly increased under phototoxic doses of TA and CPZ(P<0.05), a phenomenon not observed in other testing methods. In phototoxicity assays using guinea pig and artificial skin models, similar expression pattern changes were observed for p38 and Erk1/2.
CONCLUSION
p38 and Erk1/2 have obvious dose dependence and high sensitivity in the 3T3 NRU phototoxicity test, and can be considered as potential molecular markers for evaluating the phototoxicity of 3T3 NRU. However, they have not been feasible in guinea pig tests and EpiKutis artificial skin tests. Guinea pigs and EpiKutis artificial skin exhibit more similar changes in p38 and Erk1/2 expression, suggesting that the EpiKutis artificial skin model test method may be a better alternative to animal testing than the 3T3 NRU method.