Apoptosis Mechanism of Emodin on Renal Toxicity in Mice
10.13422/j.cnki.syfjx.20182421
- VernacularTitle: 大黄素对小鼠肾脏毒性表现的凋亡机制
- Author:
Wan-yi HUANG
1
;
Yan-qiao LI
1
;
Qing JIANG
1
;
Yu LUO
1
;
Xiao-peng AI
1
;
Ping WANG
1
;
Xian-li MENG
1
Author Information
1. College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Publication Type:Research Article
- Keywords:
emodin;
long-term toxicity;
nephrotoxicity;
oxidative stress
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(11):42-47
- CountryChina
- Language:Chinese
-
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 (P<0.05,P<0.01); activity of SOD was decreased significantly (P<0.05, P<0.01); content of TNF-α was increased significantly (P<0.05, P <0.01), while the content of GSH-Px and the ratio of GSH/GSSG were decreased significantly in high emodin group(P<0.05), and the expression of Caspase-3 was increased significantly in high emodin group (P<0.05). Renal histopathology:tubule epithelial cells swelling, tubulointerstitial protein tube type, hyperemia and lymphocytic small focal hyperplasia were observed in emodin high dose group, but the performance above was not obvious in low dose group. Conclusion: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.
