Toxicity Studies Of Xiaoyanlidan Capsule In Rodent Animals

Objective:To observe toxicity effects, target organs and NOAEL(no observed adverseeffect level) of Xiaoyanlidan Capsule, acute toxicity study and long term toxicitystudy were conducted. These studies would be a guidance on clinical studies.Methods:Acute toxicity study: 60 (30 males, 30 females) mice were randomized into 6groups (5 males and 5 females, 10 rats/group). Animals in each group wereadministered Xiaoyanlidan Capsule at single dose(10.0, 7.0, 4.9, 3.4, 2.4, 1.7 g/kg),and then monitored the toxicity effects for 14 days.Long term toxicity study: 120 wistar rats (60 males, 60 females) wererandomized into four groups (15 males and 15 females, 30 rats/group). Animals ineach group were daily administered Xiaoyanlidan Capsule once on dose levels of 0(olive oli), 0.25, 1.0, 2.5 g/kgbw for 90 days and monitored the changes of bodywieght, blood biochemistry, hematology, organ indexes and histopathology.Results:Acute toxicity study: The LD₅₀ of Xianyanlidan Capsule was 4.82 g/kg and 95%confidence interval was 3.99～5.88 g/kg.Long term toxicity study: All animals survived. One or two hours after drugadministration, the treated aniamls became sweating. The hair of the treated groups were getting dirty and droping, but it was not very serious. These changes showedapparent dose-dependence.Body weights demonstrated the general health condition of animals and the toxiceffects which caused by the drug in test. In present study showed that XiaoyanlidanCapsule would slow down body weight gain in rats. In administration period, bodyweights among groups were significantly different in statistics. Body weight gain ofthe treated were slower than the olive-oil. In withdrawal period, body weight gain ofthe treated (males and females) became faster, but body weights among males werestill significantly different in statistics because of the relatively slow growth rate ofthe high-dose group demonstrated in multiple comparions. In the same time, bodyweights of the female showed no difference in statistics. In a word, XiaoyanlidanCapsule would reduced body weight gain in rats, and this interfere could disappear inthe convalescent stage. The food consumptions of all groups kept on the same levelthroughout the whole study.Blood biochemistry and hematology were tested to evaluate the effects ofXiaoyanlidan Capsule on organ system's funtions. The treated groups showedchanges in parameters of WBC, NEU, MONO, EOS, PLT, PT, Na⁺, CR, ALT, TP, G,TG, CHOL, which were generally dose-related and considered to be of toxicologicalsignificance. It's thought to be of toxic effects of Xiaoyanlidan Capsule. Theincreases of WBC, NEU, MONO, EOS and PLT were usually found in infectiousdiseases, organ damages and tissue necrosis, allergic responses, intoxications andtumors. ALT is measured to see if the liver is damaged or diseased. Low levels ofALT are normally found in the blood. However, when the liver is damaged ordiseased, it releases ALT into the bloodstream, which makes ALT levels go up. Mostincreases in ALT levels are caused by liver damage. So ALT(aminotransferase) level inthe blood is an important and sensitive clue to liver damage. In present study, the ALT levels ofthe treated increased showed the liver damaged which probably caused by Xiaoyanlidan Capsule.The high levels of blood CHOL and low levels of blood TG in the treated group compared to thatof the contral demonstrated that the liver were damaged and/or the secretion of bile weredysfunction.Abnormality of organ index could be of toxicological effects of Xiaoyanlidan Capsule. Liver weights and liver indexes of the treated were significantly increased,which were thought to be of the toxicological effects of Xiaoyanlidan Capsule.There were not visible changes found in organs by autopsy. By histopathologicalexamination, changes were found in liver tissues of the treated probably caused byXianyanlidan Capsule. Fatty changes, acidophilia changes, puffing changes and punctiformnecrosis were found in liver cells.The changes mentioned above became normal after the withdrawal period. Itdemonstrated that the damage to the experiment animals could heal and no delayedtoxicity effects were found.The results mentioned above demonstrated that the toxicity target organ ofXiaoyanlidan Capsule in rats was liver. In two weeks' withdrawal period, the damagein liver could heal. The no observed adverse effect level (NOAEL) was considered tobe 0.25 g/kg BW.Conclusions:The safety of Xiaoyanlidan Capsule had been demonstrated in acute toxicitystudy and long term toxicity study. It is safe to orally administer XiaoyanlidanCapsule on the recommended dose level. This studies provides toxicity informationsof Xiaoyanlidan Capsule for clinical studies.