1.Toxicokinetics and tissue distribution of alpha-amanitin in rats
Yumei LU ; Xuxian FU ; Fang LUO ; Enjin ZHU ; Gen XIONG ; Jinyang ZHAO ; Tinghao FU ; Shengjie NIE ; Rui WANG ; Shuhua LI
Chinese Journal of Pharmacology and Toxicology 2024;38(1):39-45
OBJECTIVE To study the toxicokinetics and tissue distribution characteristics of alpha-amanitin in rats.METHODS The tail venous blood was collected from SD rats before and 5,10,20,30 and 45 min,1,1.5,2.5,4 and 8 h after intraperitoneal injection of alpha-amanitin(1.5 mg·kg-1),and the concentration of alpha-amanitin in blood was determined by liquid chromatography-mass spectrometry(LC-MS/MS).DAS 2.0 software was used to analyze and plot the drug-time curve with toxicokinetic parame-ters.Based on the toxicokinetics results,18 SD rats were randomly divided into three groups.The rats were sacrificed,and left ventricular arterial(LVA)blood and 9 types of tissue samples involving the heart,liver,spleen,lung,kidney,whole brain,small intestine,stomach wall and testis were collected 15 min,40 min and 2.5 h after dosing,and the concentrations of alpha-amanitin were measured by LC-MS/MS to obtain the tissue distribution results of alpha-amanitin in SD rats.RESULTS Toxicokinetics studies revealed that the peak blood concentration(Cmax)was(633±121)μg·L-1,the elimination half-life(T1/2)was(0.72±0.37)h,and the peak time(Tmax)was(0.52±0.16)h.The total clearance rate(CLz)was(1.62±0.26)L·h·kg-1,the area under the curve(AUC0-t)was(946±183)μg·h·L-1,and the mean reten-tion time(MRT0-t)was(1.18±0.17)h.The apparent volume of distribution(Vz)was(1.65±0.86)L·kg-1.The results of tissue distribution study showed that alpha-amanitin was widely distributed in SD rats with the highest concentration in the kidney,followed by the lung,small intestines,stomach wall,LVA blood and liver,but was low in the heart,spleen,testicles and other tissues,and very low in the brain.Alpha-amanitin was absorbed and eliminated quickly,peaked at 40 min in each tissue,and the concen-tration was minimized after 2.5 h.CONCLUSION The absorption and elimination of alpha-amanitin by intraperitoneal injection are rapid in SD rats,and the blood concentration reaches the peak about 31 min after administration,but can not be detected 4 h later.Alpha-amanitin is mainly distributed in the kidney,followed by the tissues and metabolic organs with rich blood flow,such as the lung,small intestines,stomach wall,LVA blood and liver.The content of alpha-amanitin is low in the heart,spleen,testicles and other tissues,and very low in the brain.It is speculated that it may have toxic targeting effect on the kidney and low blood-brain barrier permeability.
2.Design and experiment of a multi-modal electroencephalogram-near infrared spectroscopy helmet for simultaneously acquiring at the same brain area.
Xin XIONG ; Yunfa FU ; Xiabing ZHANG ; Song LI ; Baolei XU ; Xuxian YIN
Journal of Biomedical Engineering 2018;35(2):290-296
Multi-modal brain-computer interface and multi-modal brain function imaging are developing trends for the present and future. Aiming at multi-modal brain-computer interface based on electroencephalogram-near infrared spectroscopy (EEG-NIRS) and in order to simultaneously acquire the brain activity of motor area, an acquisition helmet by NIRS combined with EEG was designed and verified by the experiment. According to the 10-20 system or 10-20 extended system, the diameter and spacing of NIRS probe and EEG electrode, NIRS probes were aligned with C3 and C4 as the reference electrodes, and NIRS probes were placed in the middle position between EEG electrodes to simultaneously measure variations of NIRS and the corresponding variation of EEG in the same functional brain area. The clamp holder and near infrared probe were coupled by tightening a screw. To verify the feasibility and effectiveness of the multi-modal EEG-NIRS helmet, NIRS and EEG signals were collected from six healthy subjects during six mental tasks involving the right hand clenching force and speed motor imagery. These signals may reflect brain activity related to hand clenching force and speed motor imagery in a certain extent. The experiment showed that the EEG-NIRS helmet designed in the paper was feasible and effective. It not only could provide support for the multi-modal motor imagery brain-computer interface based on EEG-NIRS, but also was expected to provide support for multi-modal brain functional imaging based on EEG-NIRS.