Study on mechanism of bortezomib inducing peripheral neuropathy and the reversing effect of reduced glutathione.
- Author:
Hong-tao WANG
1
;
Zhuo-gang LIU
;
Wei YANG
;
Ai-jun LIAO
;
Rong ZHANG
;
Bin WU
;
Hui-han WANG
;
Kun YAO
;
Ying-chun LI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Boronic Acids; adverse effects; Bortezomib; Female; Glutathione; therapeutic use; Peripheral Nervous System Diseases; chemically induced; metabolism; prevention & control; Pyrazines; adverse effects; Rats; Rats, Wistar; Reactive Oxygen Species; metabolism
- From: Chinese Journal of Hematology 2011;32(2):107-111
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the mechanism of bortezomib inducing peripheral neuropathy and the reversing affection of reduced glutathione.
METHODSFemale Wistar rats were randomly divided into three groups. Group 1, treatment with bortezomib; Group 2, treatment with bortezomib and reduced glutathione; Group 3, saline control group. Drugs were administrated on the 1st, 4th, 7th and 11th day for the three groups. The amorphous of sciatic nerve and dorsal root ganglion (DRG) were observed by electron microscope on 14th and 42nd day. On 14th day, laser confocal microscopy was used to detect reactive oxygen species (ROS) of DRG neuron obtained from the rats by treated with DCFH-DA after primary culture.
RESULTSOn 14th day, morphology of sciatic nerve and DRG changed in both group 1 and 2. On 42nd day, the amorphous became normally in group 1. On 14th day, ROS releasing from DRG neuron was increased obviously in group 1 (P < 0.01), while decreased in both group 2 and 3, and the difference between the latter two groups had no statistical significance (P = 0.210).
CONCLUSIONReleasing ROS to injure mitochondrion and endoplasmic reticulum maybe involved in bortezomib induced peripheral neuropathy. Although reduced glutathione can inhibit ROS release, it has no obviously reversal effect for peripheral neuropathy.