Oral chronic toxicity study of geniposide in rats

Publication date: 1 March 2018
Source:Journal of Ethnopharmacology, Volume 213
Author(s): Jingzhuo Tian, Yan Yi, Yong Zhao, Chunying Li, Yushi Zhang, Lianmei Wang, Chen Pan, Jiayin Han, Guiqin Li, Xiaolong Li, Jing Liu, Nuo Deng, Yue Gao, Aihua Liang
Ethnopharmacological relevanceGeniposide, the major active constituent of Fructus Gardeniae (FG), has been widely used to treat various diseases in China.Aim of the studyThis chronic toxicity study was conducted to investigate the safety of geniposide.Materials and methodsGeniposide was administered to Sprague-Dawley (SD) rats of both sexes by oral gavage at dosages of 25, 50, or 100mg/kg in a volume of 10mL/kg once daily for 26 weeks. Endpoints included clinical observations, food consumption, body weights, blood biochemistry, haematology, and histomorphological observations.ResultsThe administration of geniposide did not influence animal mortality, the general conditions of the animals, body weights or food consumption. After 4 weeks of administration, significant toxicity was not observed. However, in the 13th week of the toxicity study, a few haematological parameters and some relative organ weights of male rats in the 50 and 100mg/kg geniposide groups were significantly increased. The percentage of reticulocytes (Retic %) was significantly increased in male and female rats administered 100mg/kg geniposide. In addition, two female rats in the 100mg/kg geniposide group showed slight pathological changes in hepatic and renal tissues. Furthermore, in a chronic (26 weeks) toxicity study, differences were detected in alanine aminotransferase (ALT), aspartate aminotransferase (AST), sodium (Na⁺), potassium (K⁺), white blood cell (WBC), red blood cell (RBC), and haemoglobin (HGB) levels and the relative weights of the liver and spleen in male rats administered 100mg/kg geniposide. In addition, differences were detected in Retic % and the relative weights of the liver, thymus, and kidneys in female rats administered 100mg/kg geniposide. Urinalysis results from male and female rats in the 100mg/kg geniposide group revealed noticeable changes. The histopathological structures of hepatic and renal tissues in the high-dose geniposide group exhibited serious abnormalities and pigment deposition.ConclusionGeniposide affected serum biochemistry, urinalysis, and haematological parameters as well as relative organ weights. The treatment also caused noticeable pathological abnormalities in liver and kidney tissues. Therefore, administration of a high dose of geniposide (100mg/kg) for 26 weeks could induced obvious liver and kidney damage.

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