The subacute toxicity and influence on cytochrome P450 of Sargassum & Laminaria thallus by oral administration

Abstract:

This study aimed to tackle the problems about the subacute toxicity and influence on cytochromeP450(CYP) of Chinese medicine pair(CMP) of Sargassum&Laminaria thallus.Through the test design,18 SD rats,half male and half female,were randomly divided into three groups:low dose,high dose and control.All groups were treated with crude polysaccharides(extracted from Sargassum&Laminaria thallus)or saline by gavage for 2 weeks. During the dosing period,the physiological characteristics of all group members were observed regularly.Until last administration, the animals were sacrificed by anesthesia and were autopsied with the use of HE staining. Three specific probe drugs were utilized for co-incubating in rat liver microsomes to verify the activity of cytochromeP450 in liver.As the results showed,severe chronic pulmonary inflammatories were found in high dose group[86.4 g/(kg·d)]and some adaptive changes occurred in the rat liver as well(e.g.cellular swelling&dilation of hepatic sinusoid)from HE staining. On the other hand,there were no significant changes on liver microsome CYP450 under low dose[10.8 g/(kg·d)] while the high dose one had a significant inducing effect on CYP3A4.As for clinic application, the drug-drug interactions as well as hepatic and pulmonary toxicity might occur when the Chinese medicine pair of Sargassum&Laminaria thallus was taken in high dose orally.