TY - JOUR
T1 - Effects of chronic tramadol exposure on the zebrafish brain
T2 - A proteomic study
AU - Zhuo, Hui Qin
AU - Huang, Lin
AU - Huang, He Qing
AU - CAI, Zongwei
N1 - Funding Information:
This work was funded by grants from the State Natural Science Fund (no. 30870515 ), and the PCSIRT Project (IRT0941), China . We thank Professor Jonathan V. Sweedler who works at the Department of Chemistry, University of Illinois, USA for comments on this manuscript. We also thank Professor John Hodgkiss of The University of Hong Kong for assistance with the English language.
PY - 2012/6/18
Y1 - 2012/6/18
N2 - Tramadol hydrochloride (TH), has become the most prescribed opioid worldwide. However, its neurotoxicity and abuse potential are not well documented. In the present study, TH administration induced abnormal behavior and body and brain mean weight loss. Two principal metabolites O- and N-desmethyltramadol were detected in the brain tissue, and N-desmethyltramadol was the main metabolite produced. A total of 30 differential protein spots were identified using semi-quantitative 2D-PAGE and proteomic analyses, and classified into 13 categories, in which subtypes of 14-3-3 proteins, creatine kinase, ATP synthase beta chain, and tubulin were identified at the separated location on the gels 3, 3, 4, and 11 times respectively. Many TH responsive proteins have functions related to oxidative stress, including 14-3-3 proteins, creatine kinase BB, ubiquitin carboxy-terminal hydrolase L-1, ATP synthase, synaptosome-associated protein, tubulin and actin. Irrespective of oxidative damage, other pathways affected include apoptosis, energy metabolism, signal disorders, and cytoskeletal structure. Ultrastructural observation of mitochondria showed a series of morphological changes in the case of TH exposure.
AB - Tramadol hydrochloride (TH), has become the most prescribed opioid worldwide. However, its neurotoxicity and abuse potential are not well documented. In the present study, TH administration induced abnormal behavior and body and brain mean weight loss. Two principal metabolites O- and N-desmethyltramadol were detected in the brain tissue, and N-desmethyltramadol was the main metabolite produced. A total of 30 differential protein spots were identified using semi-quantitative 2D-PAGE and proteomic analyses, and classified into 13 categories, in which subtypes of 14-3-3 proteins, creatine kinase, ATP synthase beta chain, and tubulin were identified at the separated location on the gels 3, 3, 4, and 11 times respectively. Many TH responsive proteins have functions related to oxidative stress, including 14-3-3 proteins, creatine kinase BB, ubiquitin carboxy-terminal hydrolase L-1, ATP synthase, synaptosome-associated protein, tubulin and actin. Irrespective of oxidative damage, other pathways affected include apoptosis, energy metabolism, signal disorders, and cytoskeletal structure. Ultrastructural observation of mitochondria showed a series of morphological changes in the case of TH exposure.
KW - Abuse potential
KW - Metabolism
KW - Oxidative stress
KW - Proteomics
KW - Tramadol hydrochloride
UR - http://www.scopus.com/inward/record.url?scp=84861664137&partnerID=8YFLogxK
U2 - 10.1016/j.jprot.2012.03.038
DO - 10.1016/j.jprot.2012.03.038
M3 - Journal article
C2 - 22507199
AN - SCOPUS:84861664137
SN - 1874-3919
VL - 75
SP - 3351
EP - 3364
JO - Journal of Proteomics
JF - Journal of Proteomics
IS - 11
ER -