Effects of CPU 86017 (chlorobenzyltetrahydroberberine chloride) and its enantiomers on thyrotoxicosis-induced overactive endothelin-1 system and oxidative stress in rat testes

ObjectivesTo 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.MethodsAdult 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.ResultsAfter 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.ConclusionsHigh-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.