Objective:

2

To observe effect of long-term administration of rhein on the kidney toxicity of mice

and explore its possible toxic mechanism

in order to provide some basis for rational clinical drug use and further research.

Method:

2

The 30 Kunming mice (half male and half female) were randomly divided into 3 groups: control group

low-dose rhein group and high-dose rhein group (0.175

0.35 g·kg

-1

)

with 10 mice in each group. The intragastric administration lasted for 60 days. During administration

general situations of the mice were observed and recorded. Serum urea nitrogen (BUN)

creatinine (SCr)

malondialdehyde (MDA)

superoxide dismutase (SOD)

tumor necrosis factor-

α

(TNF-

α

) and interleukin-6 (IL-6) were detected after drug withdrawal. Kidney index was calculated

and glutathione peroxidase (GSH-Px) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio were measured. The kidneys were collected and histopathologically examined

and the protein expressions of transforming growth factor beta (TGF-

β

1

) and cysteine aspartic acid specific protease-3 (Caspase-3) were detected by immunohistochemistry.

Result:

2

Compared with the control group of the same sex

BUN and SCr of the administration group increased significantly(

P

<

0.05

P

<

0.01). In the high-dose group

the activity of SOD decreased significantly(

P

<

0.05

P

<

0.01)

while the expressions of TNF-

α

and Caspase-3 increased significantly(

P

<

0.05). In the male group

the renal index was significantly decreased(

P

<

0.05

P

<

0.01)

the GSH-Px content in the male high-dose group was significantly decreased(

P

<

0.05)

whereas the expression of TGF-

β

1

was increased(

P

<

0.05). The histopathological changes of kidney were observed by hematoxylin-eosin (HE) staining. In the high-dose group

protein tubules were found in renal tubule lumen

glomerular and interstitial capillary congestion

tubule epithelial cell swelling and small focal proliferation of lymphocytes

and the pathological changes were more serious in male mice. The above performances in the low-dose group was less significant than those in the high-dose group.

Conclusion:

2

The toxicity of rhein in the kidney of mice was obvious at the dose of 0.35 g·kg

-1

·d

-1

and the toxicity in male organism is more obvious. The mechanism of its potential toxicity may cause the imbalance of glutathione antioxidant system

induce excessive oxidation

trigger inflammatory reaction

activate the expression of Caspase-3

and then induce apoptosis.