[Study on analgesic and accompanying toxic and side effects of euodiae fructus based on clinical efficacy dose].
OBJECTIVE
To observe and study the toxic and side effects of water extracts from Euodiae Fructus accompanied with its efficacy analgesic dose and its mechanism, in order to provide experimental basis for the correlation between its "efficacy-toxicity".


METHODS
Mice were randomly divided into 5 groups according to weight, namely the normal group, the voltaren group, and Euodiae Fructus water extracts high, middle and low dose groups. Mice were administered with drugs for consecutively seven days, abdominally injected with acetic acid at 90 min and treated with hot plates after the last administration to establish the pain model, in order to the toxic and side effects accompanied with the efficacy. Besides toxic symptoms in mice, activities of ALT and AST, and content of BUN and Cr in serum were detected to calculate indexes in livers and kidneys. The other part of serum was collected to detect the content and activities of PGE2, MDA, SOD, NO, NOS, GSH and GSH-PX in serum.


RESULTS
Continuous oral administration of water extracts from Euodiae Fructus of efficacy dose could significantly decrease the frequency of writhe in mice and increase the hot plate pain threshold, with good dose-efficacy relationship. During the administration, mice showed such toxic symptoms as diarrhoea, idle move, dysphoria and slow growth of weight. The activities of both ALT and AST in serum and hepatic tissues were remarkably increased and the liver size remarkably increased, without notable chance in content of BUN and CR in serum. Kidney size increased in only the high dose group. The content and activities of PGE2, SOD, GSH, GSH-PX in serum notably decreased, where the content and activities of MDA, NO, NOS in serum increased. The above-mentioned changes gradually aggravated with the rise in dose. There was significant difference compared with the model group, showing 'dose-toxicity' relationship to certain extent.


CONCLUSIONS
Continuous oral administration of certain dose of water extracts from Euodiae Fructus to mice can generate the toxic and side effects in liver accompanying with the analgesic effect, and show dose-dependence relationship to some extent. Its analgesic mechanism is related to the reduction of PGE, content in blood, while its toxic mechanism is related to oxidative injury to some extent.
Shandong Academy of China Medicine, Ji'nan 250014, China.
Wei
W
Huang
Rong
R
Sun
D000700:Analgesics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D032086:Evodia; D005260:Female; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology / Q000633:toxicity; D011458:Prostaglandins E / Q000097:blood
D000700:Analgesics; D010936:Plant Extracts; D011458:Prostaglandins E