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
Objective:To study nephrotoxicity induced by long-term administration of different doses of aloe-emodin in mice, and explore its mechanism. Method:A total of 30 male and female Kunming mice were randomly divided into normal control group, and low-dose aloe-emodin group,high-dose aloe-emodin group (0.8,1.6 g·kg-1). Every dose of group was administered intragastrically for 11 weeks,twice daily. effect of serum urea nitrogen (BUN),creatinine (SCr),superoxide dismutase (SOD),malondialdehyde (MDA),Glutathione (GSH/GSSG) and Glutathione Peroxidase (GSH-Px) levels were detected by biochemical kits according to manufacturer's instruction. Enzyme-linked immune assay was used to determine serum tumor necrosis factor (TNF)-α and interleukins(IL)-6 levels. Hematoxylin eosin (HE) staining was used to detect renal pathological changes in kidney tissues, and cysteine aspartic acid specific protease(Caspase)-3 and transforming growth factor(TGF)-β1 proteins were determined by immunohistochemistry. Result:According to results,compared with normal control group,the levels of BUN and SCr in serum with high-dose aloe-emodin were increased. The renal tubules in low-dose group were mildly injured,while renal tubules and glomeruli of high-dose group were moderately damaged. Compared with normal control group,the level of SOD was significant decreased (PPPPα and IL-6 were increased,the expression of TGF-β1 protein in kidneys was increased in low-dose and high-dose groups (PConclusion:results show that 1.6 g·kg-1 aloe-emodin was administered intragastrically for 11 weeks,which had toxic effects on kidney in mice. The mechanism may be related to oxidative stress,apoptosis and TGF-β1 protein expression.
ABSTRACT
Objective:To observe the effect of long-term administration of emodin on the kidney toxicity of mice, explore its possible toxic mechanism, and provide some basis for clinical rational drug use and further research. Method:The 30 Kunming mice, half male and half female, were randomly divided into 3 groups:control group, emodin low dose group and emodin high dose groups (0.8, 1.6 g·kg-1), 10 mice in each group. Continuous intragastric administration was given for 11 weeks. During administration, the general situation of the mice was observed and recorded. After treatment, the serum urea nitrogen (BUN), creatinine (SCr), malondialdehyde (MDA), superoxide dismutase (SOD) tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were detected. Kidney index was calculated and glutathione peroxidase (GSH-Px) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio were measured. The kidneys were taken for histopathological examination and the protein expression levels of transforming growth factor-β1(TGF-β1) and cysteine aspartic acid specific protease-3 (Caspase-3) were then detected by immunohistochemistry assay. Result:As compared with control group of the same sex, the weight of mice in the administration groups was decreased significantly, renal index was decreased while BUN and SCr levels were increased significantly (PPPPα was increased significantly (PP PPConclusion:The long-term administration of emodin at a large dose would show toxicity effect on mice kidney, and the toxicity was obvious at the dose of 1.6 g·kg-1·d-1, but there was no significant difference between the sexes. The mechanism of its potential toxicity may be related to the disorder of oxidation system, the injury of oxidative stress, the triggering of inflammatory reaction, and the apoptosis of cells.