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Effect of Geniposide on Liver Injury and Bile Acid Profile in Serum, Liver and Excrement of Rats / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 63-75, 2021.
Article in Chinese | WPRIM | ID: wpr-906424
ABSTRACT

Objective:

To investigate the hepatotoxicity of different doses of geniposide on the liver of rats and the effects on bile acid profile in serumliver tissue and feces.

Method:

The 60 Sprague Dawley rats, half male and half female, were randomly divided into 5 groups according to body weight: blank group and four different doses (50, 100, 200, 400 mg·kg<sup>-1</sup>) geniposide groups, 12 rats in each group. The rats were treated by gavage once a day for 7 consecutive days, and the serumliver and cecal contents were collected on the 8<sup>th</sup> day of treatment. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), the contents of albumin (ALB), total bilirubin (TBIL), total bile acid (TBA), creatinine (Crea) and carbamideUrea) were detected in each group. The sections of liver tissue were stained with hematoxylin-eosin(HE), and the protein expressions of cytokeratin 7(CK7) and cytokeratin 19(CK19) were detected by immunohistochemistry. The protein expressions of CK7 and CK19 in the liver tissue were detected by Western blot. And the mRNA expressions of cholesterol 7<italic>α</italic>-hydroxylase (CYP7A1), cholesterol 27<italic>α</italic>-hydroxylase ( CYP27A1) and cholesterol 12<italic>α</italic>-hydroxylaseCYP8B1) were detected by real-time PCR. The contents of 18 kinds of bile acids in serumliver and cecal contents were determined by ultra-performance liquid chromatography-mass spectrometry(UPLC-MS).

Result:

Compared with the control group, TBIL level in each dose of geniposide group was increasesd significantly (<italic>P</italic><0.01). ALT, AST activity and TBA content in 400 mg·kg<sup>-1</sup> geniposide group were increased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01). HE staining showed that, compared with control group, there was bile duct reaction in the portal area and inflammatory cells infiltrate around bile duct in 200 mg·kg<sup>-1</sup> and 400 mg·kg<sup>-1</sup> geniposide groups, especially 400 mg·kg<sup>-1</sup>. The expressions of CK7 and CK19 in liver tissue of 400 mg·kg<sup>-1</sup> geniposide group were significantly higher than those in the control group (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the control group, the contents of glycoursodeoxycholic acid (GUDCA) and glycohyodeoxycholic acid (GHDCA) in liver tissue of 400 mg·kg<sup>-1</sup> geniposide group decreased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01), the contents of sodium taurochenodeoxycholate (TCDCA), hyodeoxycholic acid (HDCA), cholic acid (CA) and chenodeoxycholic acid (CDCA) in liver tissue increased significantly (<italic>P</italic><0.01), the contents of glycocholic acid hydrate (GCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid hydrate (GDCA), glycocholic acid (GLCA), tauroursodeoxycholic acid (TUDCA), GUDCA, GHDCA, ursodeoxycholic (UDCA) and taurolithocholic acid (TLCA) decreased, the proportions of TCDCA, HDCA, CA, CDCA and deoxycholic acid (DCA) in liver tissue increased, the contents of GHDCA and lithocholic acid (LCA) in serum decreased significantly (<italic>P</italic><0.01), while sodium taurohyodeoxycholate hydrate (THDCA), taurocholic acid (TCA), GCA, TCDCA, UDCA, CA, CDCA, DCA in serum decreased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01). The contents of CA, UDCA, CA, CDCA and DCA increased significantly (<italic>P</italic><0.05), the ratio of CA/DCA increased significantly (<italic>P</italic><0.05), and the ratio of CA and CDCA increased by 19.60% and 4.63%, respectively; Compared with the control group, the contents of all bile acids in cecal contents of 400 mg·kg<sup>-1</sup> were decreased, and the contents of GCA, UDCA, HDCA, GCDCA, GDCA, TLCA, GLCA, CDCA, DCA and LCA were decreased significantly (<italic>P</italic><0.05, <italic>P</italic><0.01). In addition, real-time PCR results showed that the mRNA expressions of CYP7A1, CYP27A1 in the 400 mg·kg<sup>-1</sup> geniposide group were significantly higher than those in the control group (<italic>P</italic><0.05, <italic>P</italic><0.01).

Conclusion:

The 400 mg·kg<sup>-1 </sup>geniposide can cause obvious hepatotoxicity in rats, and the bile acid profile in liverserum and excrement changes significantly, and the changes of the each bile acid in liverserum and feces are different. However, the causal relationship between the gardenoside-induced liver injury and the changes in bile acid profile are<italic> </italic>not clear. It needs to be further studied.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article