1.Catalytic metalloporphyrin protects against MPTP-induced Parkinson's disease in mice
Ping CHEN ; Bin HE ; Zi-Sheng AI ; Xiao-Chu LOU ; Ang LI ; Zhen CHEN ; Xiao-Kang WU ; Li-Ping LIANG
Academic Journal of Second Military Medical University 2008;29(1):36-41
Objective: To observe the effects of manganese( Ⅲ ) meso-tetrakis (N, N'-diethylimidazolium-2-yl) porphyrin (MnTDM) in treatment of early Parkinson's disease(PD) mouse model induced by subcutaneous injection of 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine(MPTP) and to discuss its possible mechanism. Methods:Forty male C57BL/6 mice were evenly randomized into 4 groups: MPTP model group(subcutaneous injection of 25 mg/kg MPTP for 3 days), MnTDM+ MPTP group (15 mg/kg MnTDM was subcutaneously injected 1 h before MPTP injection), MnTDM control group, and normal saline group. Performance of animals in the pole and swimming test was observed 3 days after the last injection. Levels of dopamine (DA) and its metabolites(3,4-dihydroxyphenylacetic acid [DOPAC] and homovanillic acid [HVA]) in the striatum of animals were measured by high-performance liquid chromatography with an electrochemical detector(HPLC-ECD). Thiobarbituric acid (TBA) method was used to examine the levels of malondialdehyde(MDA). Results: Acute injection of MPTP could be used for establishment of PD model. The striatal levels of DA, DOPAC and HVA in MPTP group were significantly lower(P<0.01)and the striatal level of MDA was significantly higher(P<0.05) than those of the control group. MPTP had no obvious effect on the behavioral performance of the animals in a short term. MnTDM could partly inhibit the above effects of MPTP. Compared with MPTP group, MnTDM+ MPTP group had significantly higher DA, DOPAC, and HVA levels and significantly lower MDA level(all P<0.05). There was no significant difference in the behavioral indices of animals between the 4 groups. Conclusion:MnTDM can inhibit lipid peroxidation and promote DA production; it has preventive and therapeutic effects on MPTP induced PD.
2.Catalytic metalloporphyrin protects against paraquat neurotoxicity in vivo.
Ping CHEN ; Zhen CHEN ; Ang LI ; Xiao-Chu LOU ; Xiao-Kang WU ; Chun-Jun ZHAO ; Shi-Long WANG ; Li-Ping LIANG
Biomedical and Environmental Sciences 2008;21(3):233-238
OBJECTIVETo examine the neuroprotective effects of a novel manganese porphyrin, manganese (III) meso-tetrakis (N,N'-diethylimidazolium-2-yl) porphyrin (MnTDM), in the mouse model of Parkinson's disease (PD) induced by paraquat (PQ).
METHODSMale C57BL/6 mice were subcutaneously injected with either saline or PQ at 2-day intervals for a total of 10 doses, MnTDM was subcutaneously injected with the PQ 2 h before treatment. Performance on the pole and swim test were measured 7 days after the last injection and animals were sacrificed one day later. Levels of dopamine (DA) and its metabolites in the striatum were measured by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD). Thiobarbituric acid (TBA) method was used to assay the lipid peroxidation product, malondialdehyde (MDA), and the number of tyrosine hydroxylase (TH) positive neurons was estimated using immunohistochemistry.
RESULTSPretreatment with MnTDM significantly attenuated PQ-impaired behavioral performance, depleted dopamine content in striata, increased MDA, and dopaminergic neuron loss in the substantia nigra.
CONCLUSIONSOxidative stress plays an important role in PQ-induced neurotoxicity which can be potentially prevented by manganese porphyrin. These findings also propose a possible therapeutical strategy for neurodegenerative disorders associated with oxidative stress such as PD.
Animals ; Antioxidants ; therapeutic use ; Antiparkinson Agents ; therapeutic use ; Behavior, Animal ; drug effects ; Catalysis ; Corpus Striatum ; drug effects ; metabolism ; Dopamine ; metabolism ; Male ; Malondialdehyde ; metabolism ; Metalloporphyrins ; therapeutic use ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents ; therapeutic use ; Paraquat ; Parkinson Disease ; drug therapy ; metabolism ; physiopathology ; Substantia Nigra ; drug effects ; enzymology ; Tyrosine 3-Monooxygenase ; metabolism
3.Cyto-genotoxicity induced by cigarette smoke condensates in human peripheral blood lymphocytes in vitro.
Jian-lin LOU ; Guo-jun ZHOU ; Guo-hai CHU ; Fang-fang HUANG ; Jian JIANG ; Shu ZHENG ; Ye-zhen LU ; Xiao-xue LI ; Zhi-jian CHEN ; Ji-liang HE
Chinese Journal of Industrial Hygiene and Occupational Diseases 2009;27(3):140-144
OBJECTIVETo investigate the cyto-genotoxicity of cigarette smoke condensates (CSCs) in human peripheral blood lymphocytes with different assays in vitro.
METHODSHuman lymphocytes were exposed to particle matter of cigarette smoke combined with or without S9 mixtures at doses of 25, 50, 75, 100 and 125 microg/ml for 3 h. The cytotoxicity induced by CSCs was detected by CCK-8 assay. The DNA damage, DNA repair (repair time: 30, 60, 90, 120 and 240 min, respectively) and the somatic cell mutations induced by 75 microg/ml CSCs were measured by comet assay, hprt gene and TCR gene mutation tests, respectively.
RESULTSCCK-8 assay indicated that the cell viability decreased with CSCs doses. At the doses of 100, 125 microg/ml, the cell viability of CSCs +S9 group was significantly higher than that of CSCs -S9 group (P < 0.05, P < 0.01). In comet assay, DNA damage significantly increased in a dose-dependent manner, as compared with controls (P < 0.01). Moreover, there was significant difference between -S9 group and +S9 group (P < 0.05, P < 0.01). The Mf-TCR at each dose group was significantly higher than that of controls (P < 0.05, P < 0.01). The Mf-hprt at high-dose groups were significantly higher than that of controls (P < 0.01), and significant difference of Mf-TCR and Mf-hprt at high doses of CSCs between -S9 group and +S9 group (P < 0.05, P < 0.01). The DNA damage induced by CSCs +S9 or CSCs -S9 could be repaired, but DNA repair speed was different between -S9 group and +S9 group (P < 0.05, P < 0.01).
CONCLUSIONCSCs may induce cyto-genotoxicity in human peripheral blood lymphocytes in vitro, but S9 mix could reduce the toxicity of CSCs and impact DNA repair speed.
Cells, Cultured ; Comet Assay ; DNA Damage ; drug effects ; DNA Repair ; drug effects ; Humans ; Lymphocytes ; drug effects ; Male ; Mutation ; Tobacco Smoke Pollution ; adverse effects ; Young Adult
4.Effect and influence factors of cardiopulmonary resuscitation in children with congenital heart disease in pediatric intensive care unit.
Gang LIU ; Jian Ping CHU ; Jian Li CHEN ; Su Yun QIAN ; Dan Qun JIN ; Xiu Lan LU ; Mei Xian XU ; Yi Bing CHENG ; Zheng Yun SUN ; Hong Jun MIAO ; Jun LI ; Sheng Ying DONG ; Xin DING ; Ying WANG ; Qing CHEN ; Yuan Yuan DUAN ; Jiao Tian HUANG ; Yan Mei GUO ; Xiao Na SHI ; Jun SU ; Yi YIN ; Xiao Wei XIN ; Shao Dong ZHAO ; Zi Xuan LOU ; Jing Hui JIANG ; Jian Sheng ZENG
Chinese Journal of Pediatrics 2022;60(3):197-202
Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ2=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ2=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation
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Child
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Child, Preschool
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Female
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Heart Arrest/therapy*
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Heart Defects, Congenital/therapy*
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Humans
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Intensive Care Units, Pediatric
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Male
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Retrospective Studies