1.Experimental study on the toxicokinetics and gastrointestinal damage in rats poisoned with acute diquat poisoning at different exposure doses.
Jianshuang ZHANG ; Yiqing SUN ; Hengbo GAO ; Lin YUAN ; Dongqi YAO ; Liang LIU ; Baopu LYU ; Yingping TIAN
Chinese Critical Care Medicine 2023;35(6):651-657
OBJECTIVE:
To observe the toxicokinetic parameters, absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat (DQ).
METHODS:
Ninety-six healthy male Wistar rats were randomly divided into a control group (six rats) and low (115.5 mg/kg), medium (231.0 mg/kg) and high (346.5 mg/kg) dose DQ poisoning groups (thirty rats in each dose group), and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure (15 minutes and 1, 3, 12, 36 hours; six rats in each subgroup). All rats in the exposure groups were given a single dose of DQ by gavage. Rats in the control group was given the same amount of saline by gavage. The general condition of the rats was recorded. Blood was collected from the inner canthus of the eye at 3 time points in each subgroup, and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens. DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry (UPHLC-MS), and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters; the morphological structure of the intestine was observed under light microscopy, and the villi height and crypt depth were determined and the ratio (V/C) was calculated.
RESULTS:
DQ was detected in the plasma of the rats in the low, medium and high dose groups 5 minutes after exposure. The time to maximum plasma concentration (Tmax) was (0.85±0.22), (0.75±0.25) and (0.25±0.00) hours, respectively. The trend of plasma DQ concentration over time was similar in the three dose groups, but the plasma DQ concentration increased again at 36 hours in the high dose group. In terms of DQ concentration in gastrointestinal tissues, the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours. By 36 hours after poisoning, the concentrations of DQ in all parts of the stomach and intestine in the low and medium dose groups had decreased to lower levels. Gastrointestinal tissue (except jejunum) DQ concentrations in the high dose group tended to increase from 12 hours. Higher doses of DQ were still detectable [gastric, duodenal, ileal and colonic DQ concentrations of 6 400.0 (1 232.5), 4 889.0 (6 070.5), 10 300.0 (3 565.0) and 1 835.0 (202.5) mg/kg respectively]. Light microscopic observation of morphological and histopathological changes in the intestine shows that acute damage to the stomach, duodenum and jejunum of rats was observed 15 minutes after each dose of DQ, pathological lesions were observed in the ileum and colon 1 hour after exposure, the most severe gastrointestinal injury occurred at 12 hours, significant reduction in villi height, significant increase in crypt depth and lowest V/C ratio in all segments of the small intestine, damage begins to diminish by 36-hour post-intoxication. At the same time, morphological and histopathological damage to the intestine of rats at all time points increased significantly with increasing doses of the toxin.
CONCLUSIONS
The absorption of DQ in the digestive tract is rapid, and all segments of the gastrointestinal tract may absorb DQ. The toxicokinetics of DQ-tainted rats at different times and doses have different characteristics. In terms of timing, gastrointestinal damage was seen at 15 minutes after DQ, and began to diminish at 36 hours. In terms of dose, Tmax was advanced with the increase of dose and the peak time was shorter. The damage to the digestive system of DQ is closely related to the dose and retention time of the poison exposure.
Animals
;
Male
;
Rats
;
Diquat/toxicity*
;
Gastrointestinal Diseases
;
Intestines
;
Poisons
;
Rats, Wistar
;
Toxicokinetics
2.Effects of arsenic and its main metabolites on A549 cell apoptosis and the expression of pro-apoptotic genes Bad and Bik.
Qian ZHOU ; Jin Yao YIN ; Jing Wen TAN ; Shu Ting LI ; Cheng Lan JIANG ; Yue Feng HE
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(9):661-667
Objective: To investigate the effect of arsenic and its main metabolites on the apoptosis of human lung adenocarcinoma cell line A549 and the expression of pro-apoptotic genes Bad and Bik. Methods: In October 2020, A549 cells were recovered and cultured, and the cell viability was detected by the cell counting reagent CCK-8 to determine the concentration and time of sodium arsenite exposure to A549. The study was divided into NaAsO(2) exposure groups and metobol: le expoure groups: the metabolite comparison groups were subdivided into the control group, the monomethylarsinic acid exposure group (60 μmol/L) , and the dimethylarsinic acid exposure group (60 μmol/L) ; sodium arsenite dose groups were subdivided into 4 groups: control group (0) , 20, 40, 60 μmol/L sodium arsenite NaAsO(2). Hoechst 33342/propidium iodide double staining (Ho/PI) was used to observe cell apoptosis and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of Bad and Bik mRNA in cells after exposure. Western blotting was used to detect the protein expressions of Bad, P-Bad-S112, Bik, cleaved Bik and downstream proteins poly ADP-ribose polymerase PARP1 and cytochrome C (Cyt-C) , using spectrophotometry to detect the activity changes of caspase 3, 6, 8, 9. Results: Compared with the control group, the proportion of apoptotic cells in the 20, 40, and 60 μmol/L NaAsO(2) dose groups increased significantly (P<0.01) , and the expression levels of Bad, Bik mRNA, the protein expression levels of Bad, P-Bad-S112, Bik, cleaved Bik, PARP1, Cyt-C were increased (all P<0.05) , and the activities of Caspase 3, 6, 8, and 9 were significantly increased with significantly differences (P<0.05) . Compared with the control group, the expression level of Bad mRNA in the DMA exposure group (1.439±0.173) was increased with a significant difference (P=0.024) , but there was no significant difference in the expression level of Bik mRNA (P=0.788) . There was no significant differences in the expression levels of Bad and Bik mRNA in the poison groups (P=0.085, 0.063) . Compared with the control group, the gray values of proteins Bad, Bik, PARP1 and Cyt-C exposed to MMA were 0.696±0.023, 0.707±0.014, 0.907±0.031, 1.032±0.016, and there was no significant difference between the two groups (P=0.469, 0.669, 0.859, 0.771) ; the gray values of proteins Bad, Bik, PARP1 and Cyt-C exposed to DMA were 0.698±0.030, 0.705±0.022, 0.908±0.015, 1.029±0.010, and there was no difference between the two groups (P=0.479, 0.636, 0.803, 0.984) . Conclusion: Sodium arsenite induces the overexpression of Bad and Bik proteins, initiates the negative feedback regulation of phosphorylated Bad and the degradation of Bik, activates the downstream proteins PARP1, Cyt-C and Caspase pathways, and mediates the apoptosis of A549 cells.
A549 Cells
;
Adenosine Diphosphate Ribose/pharmacology*
;
Apoptosis
;
Apoptosis Regulatory Proteins
;
Arsenic
;
Arsenites
;
Cacodylic Acid/pharmacology*
;
Caspase 3
;
Caspases/pharmacology*
;
Cytochromes c/pharmacology*
;
Humans
;
Mitochondrial Proteins/pharmacology*
;
Poisons
;
Propidium/pharmacology*
;
RNA, Messenger
;
Sincalide/pharmacology*
;
Sodium Compounds
;
bcl-Associated Death Protein/metabolism*
3.Forensic Examination of Six Homicide Injection Cases.
Yu-Lei YANG ; Dong-Chuan ZHANG ; Kai-Jun MA
Journal of Forensic Medicine 2022;38(3):324-327
OBJECTIVES:
To retrospectively analyze homicide cases of death after injection and provide reference for forensic identification.
METHODS:
Six homicide cases of death after injection which were investigated by the Criminal Investigation Team of Shanghai Public Security Bureau were collected and analyzed, including case situation, scene investigation, autopsy and other materials.
RESULTS:
The 6 cases were premeditated crimes, 5 cases took place in private spaces, and 5 cases involved the victims approached by suspects' decoy. There were no obvious abnormalities at the scene of the 6 cases. In 6 cases, the victim's body surface injury was mild or no, lividity color was abnormal, and the needlestick injury showed different manifestations from conventional medical measures.
CONCLUSIONS
Death after injection is a highly concealed crime and easy to be ignored. For the suspected injection injury found in autopsy, it is necessary to carefully examine, identify and analyze, be alert to the situation of injecting poison (drug) and do a good job in evidence fixation and material extraction.
Autopsy
;
China/epidemiology*
;
Homicide
;
Poisons
;
Retrospective Studies
4.The effect of diallyl sulfide on the lung tissue of rats poisoned by paraquat.
Y F CAO ; C JI ; J GUAN ; Y M YU ; W SONG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(6):438-441
Allyl Compounds
;
Animals
;
Lung
;
Male
;
Paraquat/pharmacology*
;
Poisons
;
Rats
;
Rats, Sprague-Dawley
;
Rats, Wistar
;
Sulfides
5.Protective Effect of Procyanidin B2 on Acute Liver Injury Induced by Aflatoxin B in Rats.
Zhi Jie DENG ; Jing Fang ZHAO ; Feng HUANG ; Gui Li SUN ; Wei GAO ; Li LU ; De Qiang XIAO
Biomedical and Environmental Sciences 2020;33(4):238-247
Objective:
This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B (AFB ) in rats.
Methods:
Forty Sprague Dawley rats were randomly divided into control, AFB , AFB + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB and AFB + PCB2 groups were intraperitoneally injected with AFB (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured.
Results:
AFB significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB .
Conclusion
Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB .
Aflatoxin B1
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toxicity
;
Animals
;
Biflavonoids
;
administration & dosage
;
pharmacology
;
Catechin
;
administration & dosage
;
pharmacology
;
Chemical and Drug Induced Liver Injury
;
drug therapy
;
etiology
;
Male
;
Poisons
;
toxicity
;
Proanthocyanidins
;
administration & dosage
;
pharmacology
;
Protective Agents
;
administration & dosage
;
pharmacology
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
6.Ion Abundance Ratios of Qualitative Analysis by GC-MS of 4 Common Drugs (Poisons.
Shao Dan LIU ; Tao MIN ; Guo Bin XIN ; Da Ming ZHANG
Journal of Forensic Medicine 2019;35(6):687-694
Objective To investigate the maximum allowable deviation of ion abundance ratios of characteristic fragment ions in common drugs (poisons) in blood by gas chromatography-mass spectrometry (GC-MS) method. Methods Four common drugs (poisons) (dichlorvos, phorate, diazepam and estazolam) were detected by GC-MS full scan mode after liquid-liquid extraction in two laboratories and under three chromatographic conditions. The deviations of ion abundance ratios of the four common drugs (poisons) in marked blood samples with concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 μg/mL were analyzed. At the same time, the false negative rates of ion abundance ratios were analyzed when the mass concentration was limit of detection (LOD), 2LOD, limit of quantitation (LOQ) and 2LOQ, and the false positive rates of ion abundance ratios were analyzed with blank blood samples. Results Under the two laboratories, four common drugs (poisons) and three kinds of chromatography conditions, the differences in deviations of the ion abundance ratios of marked blood samples were not statistically significant (P>0.05). More than 95% of the absolute deviations of the ion abundance ratios of the marked blood samples were within the range of ±10%, and more than 95% of the relative deviations were within the range of ±25%. In cases of low concentration (concentration less than 2LOQ) or low signal to noise ratio (3-15), the false negative rate was less than 5% and the false positive rate was 0% when the relative deviation was greater than 50%. Conclusion The absolute deviations of ion abundance ratios of four common drugs (poisons) in marked blood samples are advised to have a determination range within ±10%, and the determination range of relative deviations within ±25%.
Gas Chromatography-Mass Spectrometry
;
Humans
;
Ions/chemistry*
;
Limit of Detection
;
Liquid-Liquid Extraction
;
Poisons/blood*
7.Self-poisoning as a Target Group for Prevention of Suicide.
Moon Hwan KWAK ; Hyun Young KANG ; Si Jin LEE ; Kap Su HAN ; Su Jin KIM ; Eu Jung LEE ; Sung Woo LEE
Journal of The Korean Society of Clinical Toxicology 2018;16(2):93-101
PURPOSE: The Korean government has tried to decrease the suicide death rate over the last decade. Suicide attempts, particularly non-fatal attempts, are the most powerful known risk factor for a completed suicide. An analysis of suicide attempt methods will help establish the effective preventive action of suicide. Fit prevention according to the method of suicide attempt may decrease the incidence of suicide death. Self-poisoning is suggested as a major method of both suicide attempts and suicide death. The aim of this study was to determine if a self-poisoning patient is a suitable target for the prevention of the suicide. METHODS: This was retrospective analysis of a prospective cohort, which included patients who presented to the emergency department (ED) after a self-harm or suicide attempt from Jan 2013 to Dec 2017. The proportion of methods in suicide attempts, psychological consultation, and fatality according to the suicide attempt method were analyzed. The types of poison were also analyzed. RESULTS: Poisoning was the most common method of suicide attempts (52.1%). The rate of psychological consultations were 18.8% for all patients and 29.1% for poison patients (p < 0.001). The rate of mortality in poisoning was 0.6%. Psychological consultation was performed more frequently in admission cases than discharged cases. The most common materials of poisons was psychological medicines and sedatives that had been prescribed at clinics or hospital. CONCLUSION: Self-poisoning is a major method of suicide attempt with a high rate of psychiatric consultation, low mortality rate, versus others methods. The prevention of suicide death for suicide attempts may focus on self-poisoning, which is the major method of suicide attempts. A suitable aftercare program for self-poisoning may be an effective method for preventing suicide if an early diagnosis and management of psychiatric disorders through psychiatric consultation can be made, and early connection to social prevention program for non-fatal patients are possible.
Aftercare
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Cohort Studies
;
Early Diagnosis
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Emergency Service, Hospital
;
Humans
;
Hypnotics and Sedatives
;
Incidence
;
Methods
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Mortality
;
Poisoning
;
Poisons
;
Prospective Studies
;
Referral and Consultation
;
Retrospective Studies
;
Risk Factors
;
Suicide*
8.Analysis of Death Due to Poisoning in the National Capital Region (2014–2016).
Meejung PARK ; Jongsin PARK ; Sangki LEE ; Sangwhan IN
Journal of The Korean Society of Clinical Toxicology 2017;15(2):101-106
PURPOSE: This study examined the patterns of drugs, poisons, and chemicals detected in autopsy samples performed in the Seoul Institute and other regional forensic offices of the National Forensic Service (NFS) between 2014 and 2016. METHODS: The investigation carried out using the laboratory information management system. Forensic toxicological identification and quantitation were performed in autopsy samples, including heart blood, peripheral blood, liver, kidney, vitreous humor and etc. Gas chromatography/mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to analyze the drugs and poisons. RESULTS: Forensic autopsies were performed on 9,674 cases in this period. Based on the autopsy reports, 699 cases (7.2%) were considered as unnatural deaths caused by fatal intoxication. The number of male deaths was higher than that of female deaths, with the age of 50-59 being the most common age group. CONCLUSION: Drugs comprised the largest number of deaths due to poison, followed by alcohol, agrochemicals, drug with alcohol, carbon monoxide, and cyanide, in that order. Zolpidem was the most frequently used drug in all drug-related intoxication cases.
Agrochemicals
;
Autopsy
;
Carbon Monoxide
;
Female
;
Heart
;
Humans
;
Information Management
;
Kidney
;
Liver
;
Male
;
Mass Spectrometry
;
Poisoning*
;
Poisons
;
Seoul
;
Spectrum Analysis
;
Vitreous Body
9.Poisoning-induced Out-of-Hospital Cardiac Arrest and Outcomes according to Poison Agent.
Minjee KIM ; Sang Do SHIN ; Seungmin JEONG ; Young Ho KWAK ; Gil Joon SUH
Journal of Korean Medical Science 2017;32(12):2042-2050
It is unclear whether specific agent groups are associated with outcomes in cases of poisoning-induced out-of-hospital cardiac arrest (P-OHCA). The study population comprised cases of confirmed P-OHCA drawn from the national out-of-hospital cardiac arrest (OHCA) registry (2008–2013). Exposures were categorized into five groups according to the International Classification of Disease, 10th version: group 1, prescribed drugs; group 2, vapors and gases; group 3, pesticides; group 4, alcohol and organic solvents; and group 5, other poisons. The outcome was survival to discharge and good neurological recovery. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated to test the association between specific groups and outcomes. A total of 2,083 patients were analyzed; group 1 (10.3%), group 2 (23.6%), group 3 (52.9%), group 4 (1.4%), and group 5 (13.2%). The survival to discharge and good neurological recovery rates were 3.3%/1.3% for all patients, 10.3%/5.6% (group 1), 6.9%/3.4% (group 2), 2.4%/0.4% (group 3), 2.2%/1.0% (group 4), and 3.3%/2.4% (group 5) (all P < 0.001). The aORs (95% CIs) of groups 2–5 compared with group 1 for survival to discharge were 0.47 (0.09–2.51), 0.34 (0.17–0.68), 0.33 (0.14–0.77), and 0.31 (0.13–0.77), respectively. The odds ratios (95% CIs) for good neurological recovery were significant only in group 1, the pesticides group (0.07 [0.02–0.26]) and were not significant in the other groups. P-OHCA outcomes differed significantly among the poisoning agent groups. The pesticides group showed the worst outcomes, followed by the group of vapors or gases.
Classification
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Gases
;
Heart Arrest
;
Humans
;
Odds Ratio
;
Out-of-Hospital Cardiac Arrest*
;
Pesticides
;
Poisoning
;
Poisons
;
Solvents

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