Studies on the relationship between sinomenine distribution and its organic toxicology / 中国药理学通报

ABSTRACT

AIM　To investigate the relationship between sinomenine distribution and its organic toxicology in rats so as to give some pharmacological data for clinical application of sinomenine. METHODS　Three kinds of administration plans were designed in the experiment, ie sinomenine was ip administered at the dosage of l50 mg*kg-1 per day, repreat-dosed for 6 wk and suspended the drug for 1 wk after 6wk repeat-doses．At the end of the each administration plan，the animals were sacrificed and their blood and their main internal organs were collected for the purpose of measurement of sinomenine concentration in each sample by HPLC. Meanwhile，the histopathological and serological examinations were also done in the experiments. RESULTS　The sinomenine concentration in rats internal organs were in order of liver, heart, lung and brain either in single-dosed treated animals or in repeat-dosed treated animals for 6 wk. However，the concentration of sinomenine could not be detected by HPLC after l wk drug-suspension，the histopathological examination showed that sinomenine at the dosage of l50 mg*kg-l per day for 6wk treatment could slightly damage liver ce11s, dominant1y caused the cell edema，but no any influence on the sero1ogy of liver and kidney. Sinomenine ip could also cause a mild hyperaemia of the rats heart tissues but no any histopathological changes had been observed. In testis tissues no sinomenine had beed detected although the animals were treated by repeat treatment for 6 wk and no any histopathological changes had been found yet. However, Sinomenine could partialy inhibit the sperm vitalities and amount of the dead sperms were a1so augmented. It was similar to in vitro eperiments. These influences of sinomenine on testis could be quickly recovered by drug suspension. CONCLUSION　Sinomenine concentration were in order of liver, heart, kidney, lung and brain either in treatment by single dose or by repeat-dose administration. The histopathological changes were only abserved in liver cells of the animals which indicates that it should be in consideration of the liver functions during treatment course of the drug.