ABSTRACT
Objective: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: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-β1) and cysteine aspartic acid specific protease-3 (Caspase-3) were detected by immunohistochemistry. Result:Compared with the control group of the same sex, BUN and SCr of the administration group increased significantly(PPPPα and Caspase-3 increased significantly(PPPPβ1 was increased(PConclusion: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.
ABSTRACT
Rhei Radix et Rhizoma is a common medicine in clinic, which is widely used for a variety of diseases,such as constipation, jaundice, peptic ulcer, bacillary dysentery. In recent years, there have been many cases of clinical abuse and increasing number of adverse reactions about Rhei Radix et Rhizoma. Many reports concerned with its toxicity have drawn more and more attention at home and abroad. This review makes a brief summary on the toxicity research of Rhei Radix et Rhizoma in recent years in the aspects of hepatotoxicity, nephrotoxicity and its corresponding toxicity-controlling methods. Liver and kidney toxicity of Rhei Radix et Rhizoma was explained in various aspects, including liver and kidney biochemical indicators, apoptosis, mitochondrial function, gene and protein expression and signaling pathway. Besides, the attenuation methods of Rhei Radix et Rhizoma were summarized in aspects of processing and compatibility of traditional Chinese medicine. In conclusion, this study explains hepatotoxicity and nephrotoxicity of Rhei Radix et Rhizoma objectively, and explore relevant toxicological mechanisms, in order to provide proper reference for its further research and the safety of clinical use.