Back to Search
Start Over
Curcumin protects against doxorubicin induced oxidative stress by regulating the Keap1-Nrf2-ARE and autophagy signaling pathways.
- Source :
- Psychopharmacology; May2023, Vol. 240 Issue 5, p1179-1190, 12p, 2 Color Photographs, 1 Chart, 5 Graphs
- Publication Year :
- 2023
-
Abstract
- Background: Doxorubicin (DOX)-induced neurotoxicity is widely reported in previous studies. Oxidative stress has been validated as a critical event involved in DOX-induced neurotoxicity. As a selective autophagy adaptor protein, p62 is reported to regulate Keap1-Nrf2-ARE antioxidant pathway in response to oxidative stress. Curcumin (CUR) relieves depressive-like state through the mitigation of oxidative stress and the activation of Nrf2-ARE signaling pathway. However, the exact mechanism of CUR in alleviating DOX-induced neurotoxicity is still unknown. Materials and methods: The rats were randomly divided into three groups: control group, DOX group, and DOX + CUR group. At the end of 3 weeks, the behavior tests as sucrose preference test (SPT), forced swimming test (FST), and novelty-suppressed feeding test (NSFT) were performed to assess anxiety- and depression-like behaviors. The rats were sacrificed after behavior tests, and the brain tissues were collected for biochemical analysis. Results: It was observed that the administration of CUR could effectively reverse DOX-induced depressive-like behaviors. The exposure of DOX activated autophagy and increased oxidative stress levels, and the administration of CUR could significantly inhibit DOX-induced autophagy and suppress oxidative stress. More importantly, we also found that Keap1-Nrf2-ARE signaling pathway was involved in DOX-induced neurotoxicity and oxidative stress regulated by autophagy. Conclusion: Our study demonstrated that CUR could effectively reverse DOX-induced neurotoxicity through suppressing autophagy and mitigating oxidative stress and endoplasmic reticulum (ER) stress. [ABSTRACT FROM AUTHOR]
- Subjects :
- CURCUMIN
DOXORUBICIN
OXIDATIVE stress
AUTOPHAGY
CELLULAR signal transduction
Subjects
Details
- Language :
- English
- ISSN :
- 00333158
- Volume :
- 240
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 163099320
- Full Text :
- https://doi.org/10.1007/s00213-023-06357-z