Effects of CPU 86017 (chlorobenzyltetrahydroberberine chloride) and its enantiomers on thyrotoxicosis-induced overactive endothelin-1 system and oxidative stress in rat testes.
OBJECTIVE
To study the effects of CPU 86017, a berberine derivative, and its four enantiomers on thyrotoxicosis-induced oxidative stress and the excessive endothelin-1 system in rat testes.


METHODS
Adult male SD rats were given high-dose L-thyroxin (0.2 mg/kg subcutaneously) once daily for 10 days to develop thyrotoxicosis. Subsets of the rats were treated with CPU 86017 or its four enantiomers (SR, SS, RS, and RR) once daily from day 6 to day 10. The alterations of redox, nitric oxide synthase, and endothelin-1 system in testes were examined by spectrophotometry and reverse transcriptase-polymerase chain reaction assay.


RESULTS
After 10 days of high-dose L-thyroxin administration, increased mRNA expression of prepro-endothelin-1 and endothelin-converting enzyme was observed in the rat testes, accompanied by an elevated inducible nitric oxide synthase activity and oxidative stress. CPU 86017 and its enantiomer SR significantly improved these abnormalities.


CONCLUSIONS
High-dose L-thyroxin results in an overactive endothelin-1 system and oxidative stress in adult rat testis. CPU 86017 and its enantiomer SR suppressed the excessive ET-1 system by improving oxidative stress, and SR exhibited more potent efficacy than CPU 86017 and other enantiomers.
Tang
XiaoYun
X
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China.
Qi
MinYou
M
Dai
DeZai
D
Zhang
Can
C
D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019332:Endothelin-1 / Q000502:physiology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013971:Thyrotoxicosis / Q000378:metabolism*
C400084:4-chlorobenzyltetrahydroberberine; D019332:Endothelin-1; D001599:Berberine