Toxicity Studies Of Psidium Guajava Leaf Granule In Rodent Animals

Objective:TO observe toxicity effects,target organs and NOAEL(no observed adverse effect level)of Psidium guajava L Granule,acute toxicity study and long term toxicity study were conducted o These studies would be a guidance on clinical studies.Methods:Acute toxicity study:(20 males,20 females) 40 mice were randomized into 2 groups(10 mals,10 females,20 rats a group),oral maximal tolerance dose(MTD) were determined,and the times equal to human were calculated accordingly.Then monitored the toxicity effects for 14 days.Long term toxicity study:80 SD rats(40 males,40 females)were randomized into four groups(10 males and 10 females,20 rats a group).Animals in each group were daily administered Psidium guajava L Granule once on dose levels of 62.5,25,10g/kg for 30 days and monitored the changes of body weight,blood biochemistry,hematology,organ indexes and histopathology.Results:Acute toxicity study:All animals survived,the oral maximal tolerance dose of Psidium guajava L Granule was 562.5g/kg,equal to 1125 times dosage in human.Long term toxicity study:All animals survived.One or two days after drug administration,the treated animals became sweating.The hair of the treated groups were getting dirty and dropping,but it was not very serious.These changes did not show any dose dependence.Body weights demonstrated the general health condition of animals and the toxic effects which caused by the drug in test.In administration period,body weights among groups were significantly different in statistics.In the first week,body weight among males were significantly different in statistics because of the relatively slow growth rate of the control group in multiple comparions.In the same time,body weights of the females were significantly different in statistics because of the relatively slow growth rate of low-dose group in comparions of control group.In convalescence stage,body weights among males were significantly different in statistics.In the fifith week,body weight gain of the treated were faster than the control group.In the sixth week,,body weight gain of the mid-dose group were faster than other groups.In the same time, body weights of the female showed no difference in statistics.In a word,Psidium guajava L Granule has no obviously inhibition on body weight of animals.The food consumptions of all groups kept on the same level throughout the whole study.Blood biochemistry and hematology were tested to evaluate the effects of Psidium guajava L Granule on organ system's funtions.The treated groups showed changes in parameters of WBC,LYM,Cl~-,CHOL,CK,which were generally dose-related and considered to be of toxicological significance.It s thought to be of toxic effects of Psidium guajava L Granule.the increases of WBC,LYM were usually found in infectious diseases,organ damages and tissue necrosis,allergic responses, intoxications.The high levels of blood CHOL demonstrated that the liver were damaged,but the level of blood CHOL in the treated group lower than that in the contral group during administration period.Abnormality of organ index could be of toxicological effects of Psidium guajava L Granule.There were not visible changes found in organs by autopsy.By histopathological examination,changes were found in liver tissues of the treated and the control group.Fatty changes,acidophilia changes,puffing changes and punctiform necrosis were found in liver cells.interstitial pneumonia and bronchitis were found in lung tissues of the treated and the control group.The changes mentioned above became normal after the withdrawal period.Conclusions:The safety of Psidium guajava L Granule had been demonstrated in acute toxicity study and long term toxicity study.It is safe to orally administer Psidium guajava L Granule on the recommended dose level.This studies provides toxicity informations of Psidium guajava L Granule for clinical studies.