Experimental Podophyllotoxin (Bajiaolian) Poisoning:——Ⅰ. Effects on the Nervous System

Bajiaolian, one of the species in the Mayapple family ( Podophyllum pelatum ), has been widely used as a traditional Chinese herbal medicine for the remedies of snake bites, general weakness, poisons, condyloma accuminata, lymphadenopathy, and certain tumors in China. In Western medicine, Podophyllum was first used medically as a laxative in the early 19th century. Since 1940, the resin of podophyllum has also been used topically for various skin lesions, such as warts and condyloma. Human poisonings have been reported.An animal model was established to investigate the neurotoxic effects of Bajiaolian. Podophyllotoxin, the major active ingredient in Podophyllum, was injected (ip) to young adult male rats at doses of 0, 5, 10, or 15 mg-kg-1 b.w.. The animals were sacrificed 72 h after injection.Neuronal changes were readily observable in animals treated with 10 or 15 mg-kg-1 of the toxin. Edematous changes of the anterior horn motoneurons were observed in the spinal cord. No neuronal necrosis was found. The type of neuronal swelling is believed to be only a transient change and would probably subside with time if no further assaults occur. More serious and perhaps longer term of changes were found in the dorsal ganglion neurons and the nerve fibers (axons) in the central and peripheral nervous system. Severe depletion of the Nissl substance (RNA/polyribosomes) was observed in the dorsal root ganglion neurons. Alterations in these sensory neurons would give rise to and correlate with the sensory disturbances experienced by the patients. Bodian staining also revealed a dose-related increase in the coarseness (thickness) of the nerve fibers (axons) in the cerebellum, cerebral cortex, brainstem, and spinal cord.This is the first scientific study showing the neurotoxicity of Bajiaolian, a commonly used Chinese herbal medicine. Toxicities on other organ systems by this drug certainly exist. Caution should be exercised in the dispensing and usage of this medicine.

Effection of Lead Poisoning and Newcastle Disease Vaccine on Development of Egg Yellow Feather Quail

[ Objective] To investigate the effects of Newcastle disease vaccination and lead exposure on growth and development of egg yellow feather quail. [ Method] Ninety 14-day-old quails were assigned randomly to 10 groups （ n = 9）, and they fed and drunk at liberty. A 2 ×5 factorial design was used. The quail immunized with ND vaccine and those non-immunized were exposed to lead at a dosage of 0, 50,500, 1 000 and 2 000 mg/L, respectively. [Result] The ND immunization reduced body weight significantly （ P 〈 0.01 ） and increased liver index and serum levels of hy- aluronic acid in quail within 1 -2 weeks post inoculation. The quail exposed to 2 000 mg/L lead acetate had significantly lower body weight than the control （ P 〈 0.01 ）. From 7 weeks old, the same inhibitory effect was observed in the quail＇exposed to lead at different dosages （ P 〈 0.01 ）. In addition, the lead poisoning could cause decreased feed intake, depilation, gonadal dysgenesis, and increased serum levels of hyaluronic acid. [ Conduslon] The inhibitory effect of ND vaccination on growth of quail occurs within 1 -2 weeks post inoculation; thus, the effects of immune stress should not be worried in quail production. The lead poisoning has significant effects on body weight and feed intake of quail, and lead dosage and duration affect the inhibitory effects of lead. Gonadal dysgenesis is an important indicator of lead poisoning in. quail. The serum levels of hyaluronic acid can be used to determine whether the quail have been immunized with ND vaccine or have contacted lead pollutants.

Association between the HOTAIR Polymorphism and Susceptibility to Lead Poisoning in a Chinese Population

This study explored the association between the lncRNA HOTAIR polymorphism and susceptibility to lead poisoning in a Chinese population. We speculated that lead poisoning caused elevated levels of oxidative stress, which, in turn, activate the HOTAIR gene to cause apoptosis. Three lncRNA HOTAIR tagSNPs（rs7958904, rs4759314, and rs874945） were genotyped by TaqM an genotyping technology in 113 lead-sensitive and 113 lead-resistant Chinese workers exposed to lead. Rs7958904 was significantly associated with susceptibility to lead poisoning（P = 0.047）. The rs7958904 G allele had a protective effect compared with the C allele and reduced the risk of lead poisoning（P = 0.016）. Rs7958904 may act as a potential biomarker for predicting the risk of lead poisoning and distinguishing lead-sensitive individuals from lead-resistant individuals.

Extreme gastric dilation caused by chronic lead poisoning: A case report

Lead is a toxic metal that affects many organ systems and functions in humans. In the majority of adults, chronic lead poisoning comes from exposures to work places and can occur in numerous work settings, such as manufacturing, lead smelting and refinement, or due to use of batteries, pigments, solder, ammunitions, paint, car radiators, cable and wires, certain cosmetics. In some countries, lead is added to petrol. We present a rare case of gastric dilation caused by long-term petrol ingestion. A 16-year-old young man was admitted to our hospital due to a 6-mo history of exhaustion, dizziness, nausea, abdominal cramps and constipation. X-ray examination revealed dilated stomach descending into the pelvis and small bowel distension. After a long clinical observation, we found that the reason for the chronic lead poisoning of the patient was due to a 3-year history of petrol ingestion. The patient spontaneously recovered and stomach returned to its normal position and size. Lead poisoning should be taken into consideration in all unexplained cases of gastric dilation.

Lead poisoning due to appendiceal foreign body

Lead poisoning caused by a foreign body is rare. Foreign bodies that are ingested typically pass without consequence or awareness by the patient [1]. There are few documented cases of lead poisoning from an ingested foreign body lodged in the appendix. Screening for lead poisoning is mandated by New York State at annual well person exams for children ages 6 months to 6 years [2]. We present a case of a 2-year-old male who was found to have elevated lead levels during a routine well-child visit. An abdominal X-ray was obtained as part of routine follow up for elevated lead levels and a foreign body was found in the right lower quadrant. After unsuccessful attempt to flush the foreign body out with golytely, a CT abdomen/ pelvis was obtained. The foreign body was localized in the appendix. The patient was subsequently taken to surgery for an appendectomy to remove the foreign body. This case is a demonstration of the positive effects of the lead screening guidelines of New York.

Food contamination as a pathway for lead exposure in children during the 2010–2013 lead poisoning epidemic in Zamfara,Nigeria

In 2010, an estimated 400 to 500 children died of acute lead poisoning associated with artisanal gold mining in Zamfara, Nigeria. Processing of gold ores containing up to 10% lead within residential compounds put residents, especially children, at the highest risk. Principal routes of exposure were incidental ingestion and inhalation of contaminated soil and dusts. Several Nigerian and international health organizations collaborated to reduce lead exposures through environmental remediation and medical treatment. The contribution of contaminated food to total lead exposure was assessed during the environmental health response. Objectives of this investigation were to assess the influence of cultural/dietary habits on lead exposure pathways and estimate the contribution of contaminated food to children＇s blood lead levels（BLLs）. A survey of village dietary practices and staple food lead content was conducted to determine dietary composition, caloric intakes, and lead intake. Potential blood lead increments were estimated using bio-kinetic modeling techniques. Most dietary lead exposure was associated with contamination of staple cereal grains and legumes during post-harvest processing and preparation in contaminated homes. Average post-harvest and processed cereal grain lead levels were 0.32 mg/kg and 0.85 mg/kg dry weight, respectively. Age-specific food lead intake ranged from 7 to 78 μg/day. Lead ingestion and absorption were likely aggravated by the dusty environment, fasting between meals, and nutritional deficiencies. Contamination of staple cereal grains by highly bioavailable pulverized ores could account for as much as 11%–34% of children＇s BLLs during the epidemic, and were a continuing source after residential soil remediation until stored grain inventories were exhausted.

Lead poisoning in new immigrant children from the mainland of China

Objective To define the prevalence, severity and risk factors for lead poisoning in new immigrant children from the mainland of China to Hong Kong, China.Methods New immigrant children from the mainland of China under 18 years of age were invited to join the study. Their growth parameters and venous blood lead levels (BLL) were measured within 7 days of arrival. Those with elevated BLL i.e. 】10?μg/dl (0.48?μmol/L) were assessed for signs, symptoms and risk factors of lead poisoning. Education on the prevention of lead poisoning and follow up BLL measurements were offered until their BLL normalized.Results Four hundred and fifty-seven children were recruited. Among them, 18.1% and 2.6% had BLL 】0.48 and 0.71?μmol/L, respectively. None had BLL 】0.96?μmol/L. Possible risk factors included contaminated drinking water (19%), herb ingestion (17.5%), pica, playing in dumping grounds, residing near paint factories or highways, habitual inhalation of car exhaust and cooking with petroleum. Symptoms and signs included abdominal pain, headache, short stature, and learning difficulties but did not correlate with BLL. None required treatment except for counseling on the avoidance of risk factors. About 94.7% showed a reduction in BLL 2-3 months after arrival and before counseling. All had normalized BLL by 9 months except 1 who had an X-ray feature of lead line.Conclusions Lead poisoning is common in new immigrant children from the mainland of China. Environmental factors were most important while behavioral factors like regular herb ingestion might have contributed to the persistence of high BLL in the minority.

香菇糖蛋白对大鼠铅中毒的改善作用

目的:通过优化提取工艺获得具有促排铅功能的香菇糖蛋白,探讨其对醋酸铅诱导铅中毒大鼠的防治效果。方法:利用热水浸提去除蛋白以及层析技术获得香菇糖蛋白纯品,利用红外光谱分析、单糖组成、N端氨基酸及内部氨基酸序列分析技术鉴定了香菇糖蛋白的分子特性。将63只雄性SD大鼠随机分为9组,即空白对照组、模型组、阳性对照组、香菇糖蛋白处理组(4、8、160 mg/kg)和香菇子实体处理组(4、12、36 g/kg),通过腹腔注射醋酸铅制备大鼠铅中毒模型,连续给药30 d,观察大鼠的外观表现,检测体重变化、血液和脏器中的铅含量以及生化指标。结果:提纯的香菇糖蛋白(LEPP)经过单糖组成分析发现其是由葡萄糖、甘露糖、半乳糖、葡萄糖醛酸、木糖、岩藻糖、核糖、半乳糖醛酸、阿拉伯糖、鼠李糖组成,氨基酸序列分析发现其N端序列为MPEQVVVADA,说明香菇糖蛋白具有多糖和蛋白的成分。动物实验表明,香菇糖蛋白能够促进铅中毒大鼠的体重增长,显著降低血液和肝脏中铅的含量(P<0.05),具有排除铅在肝脏中的沉积作用,显著提高血清中超氧化物歧化酶(Superoxide Dismutase,SOD)和过氧化氢酶(Catalase,CAT)的活性(P<0.05),降低丙二醛(Malondialdehyde,MDA)的含量(P<0.05),提高机体的抗氧化能力,同时香菇糖蛋白还可以降低血液中谷草转氨酶(Glutamic Oxaloacetic Transaminase,AST)和谷丙转氨酶(Glutamic-Pyruvic Transaminase,ALT)的水平,具有保护肝脏的作用。结论:香菇糖蛋白可以排除体内的重金属铅,有效地改善大鼠的铅中毒症状。

基于Keap1/Nrf2/ARE信号通路探讨高良姜总黄酮对铅诱导HK-2细胞损伤的保护作用

目的 探讨高良姜总黄酮对铅(Pb)诱导人肾皮质近曲小管上皮细胞(HK-2)细胞损伤的保护作用。方法 体外培养HK-2细胞,MTT法检测不同质量浓度高良姜总黄酮和Pb对HK-2细胞活力的影响。设置对照组、高良姜总黄酮对照组、模型组和高良姜总黄酮组,除对照组和高良姜总黄酮对照组外各组均给予200μmol/L Pb诱导细胞损伤,同时高良姜总黄酮对照组和高良姜总黄酮组给予100μg/mL高良姜总黄酮干预24 h。通过Hoechst 33258荧光染色法联合annexin V-FITC/PI双标记流式细胞术检测细胞凋亡情况,荧光显微镜法观察Pb诱导及高良姜总黄酮干预对细胞内ROS水平的影响,试剂盒法检测细胞内氧化应激指标ROS、MDA、GSH水平和GSH-Px、CAT、SOD活性,ELISA法检测细胞培养上清液IL-1β、IL-6、TNF-α水平,Western bolt法检测细胞Keap1/Nrf2/HO-1信号通路相关蛋白及caspase-3蛋白表达。结果 与对照组比较,高良姜总黄酮(12.5~200μg/mL)对HK-2细胞活力没有显著影响。与模型组比较,高良姜总黄酮可减少Pb诱导HK-2细胞的凋亡(P<0.05),减轻细胞皱缩等细胞凋亡形态学变化,上调细胞内SOD、CAT、GSH-Px活性及GSH水平(P<0.05),降低细胞内MDA、ROS水平(P<0.05),上调Keap1/Nrf2/HO-1信号通路相关蛋白及caspase-3蛋白表达(P<0.05)。结论 高良姜总黄酮可能通过调控Keap1/Nrf2/ARE信号通路相关蛋白表达,对Pb诱导HK-2细胞损伤起保护作用。

Neurotoxicity and Biomarkers of Lead Exposure: a Review

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes,public health decision making,and primary prevention synthesis.Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies.Biomarkers are generally classified into three groups:biomarkers of exposure,effect,and susceptibility.The main body compartments that store lead are the blood,soft tissues,and bone;the half-life of lead in these tissues is measured in weeks for blood,months for soft tissues,and years for bone.Within the brain,lead-induced damage in the prefrontal cerebral cortex,hippocampus,and cerebellum can lead to a variety of neurological disorders,such as brain damage,mental retardation,behavioral problems,nerve damage,and possibly Alzheimer’s disease,Parkinson’s disease,and schizophrenia.This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

Chrysophanol attenuates lead exposure-induced injury to hippocampal neurons in neonatal mice

Previous studies have shown that chrysophanol protects against learning and memory impairments in lead-exposed adult mice. In the present study, we investigated whether chrysophanol can alleviate learning and memory dysfunction and hippocampal neuronal injury in lead-exposed neonatal mice. At the end of lactation, chrysophanol（0.1, 1.0, 10.0 mg/kg） was administered to the neonatal mice by intraperitoneal injection for 15 days. Chrysophanol significantly alleviated injury to hippocampal neurons and improved learning and memory abilities in the lead-poisoned neonatal mice. Chrysophanol also significantly decreased lead content in blood, brain, heart, spleen, liver and kidney in the lead-exposed neonatal mice. The levels of malondialdehyde in the brain, liver and kidney were significantly reduced, and superoxide dismutase and glutathione peroxidase activities were significantly increased after chrysophanol treatment. Collectively, these findings indicate that chrysophanol can significantly reduce damage to hippocampal neurons in lead-exposed neonatal mice.

Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate

After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise （15-22 m/min, 25-64 minutes） and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus （P = 0.04） and plasma level of total antioxidant capacity of rats exposed to lead acetate （P 〈 0.001）, and significantly decreased plasma level of malondialdehyde （P 〈 0.001）. Acute exercise only decreased the hippocampal malondialdehyde level （P = 0.09） and increased brain-derived neurotrophic factor level in the hippocampus （P = 0.66）. Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly （P = 0.99）, These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects.

Lead Can Inhibit NMDA-,K^+-,QA/KA-Induced Increases in Intracellular Free Ca^(2+) in Cultured Rat Hippocampal Neurons

Objective To examine the effects of Pb2+ on N-methyl-D-aspartate (NMDA)-, K+- and quisqualate(QA)/kainite(KA)-induced increases in intracellular free calcium concentration ([Ca2+],) in cultured fetal rat hippocampal neurons in order to explain the cognitive and learning deficits produced by this heavy metal. Methods Laser scanning confocal microscopy was used. Results The results clearly demonstrated that adding Pb2+ before or after NMDA/glycine stimulation selectively inhibited the stimulated increases in [Ca2+], in a concentration-dependent manner. In contrast, Pb2+ treatment did not markedly affect increases in [Ca2+], induced by an admixture of QA and KA. The minimal inhibitory effect of Pb2+ occurred at 1 μmol/L, and more than seventy percent abolition of the NMDA-stimulated increase in [Ca2+]; was observed at 100 Jμmoll/L Pb2+. Evaluation of Pb2+-induced increase in [Ca2+], response to elevating extracellular concentrations of NMDA, glycine or calcium revealed that Pb2+ was a noncompetitive antagonist of both NMDA and glycine, and a competitive antagonist of Ca2+ at NMDA receptor channels. In addition. Pb2+ inhibited depolarization-evoked increases in [Ca2+], mediated by K+ stimulation(30μmol/L). indicating that Pb2+ also depressed the voltage-dependent calcium channels. Also, the results showed that Pb2+ appeared to be able to elevate the resting levels of [Ca2+|, in cultured neurons, implying a reason for Pb2+-enhanced spontaneous release of several neurotransmitters reported in several previous studies. Conclusion Lead can inhibit NMDA-. K+-, QA/KA-jnduced increases in intracellular [Ca2+], in cultured hippocampal neurons.

Effect of Functional Compound Recipe Liquid of Eliminating Lead on Eliminating Lead and Calcium in Rats

The experiment was conducted to approve the efficacy of functional compound recipe liquid of eliminating lead and calcium to eliminate lead in rats.Total 120 rats were divided into six groups according to weight: blank group (CK),negative group (ND),positive group (PD) and high group (HD,6.67 Mg·kg -1·BW·d -1 ),middle group (MD,3.33 Mg·kg -1·BW·d -1 ) and low group (LD,1.67 Mg·kg -1·BW·d -1 three groups).Except CK,other groups were drunk 0.24% Pb(AC) 2 ,in which rats were filled with functional compound rec...

13例服用中药偏方致铅中毒患者诊疗分析

目的分析中药偏方致铅中毒的诊疗过程,提高对偏方致铅中毒的认识并降低误诊率。方法分析2022年5月至2023年9月泰安市公共卫生医疗中心收治的13例偏方致铅中毒患者的临床资料及诊治心得。结果13例患者均以腹绞痛、腹胀为主要就诊症状,血铅水平均高于正常值,部分患者出现蛋白尿、肝功异常、贫血等症状。经驱铅治疗后患者各项指标恢复正常。结论对有使用偏方史且出现腹绞痛、不完全肠梗阻、肝功异常、贫血等症状者,应高度怀疑偏方致铅中毒,需采取积极驱铅治疗。

Risk Assessment of Heavy Metals in Food Crops at Abandoned Lead-Zinc Mining Site at Tse-Faga, Logo, Lga, Benue State, Nigeria

Hundreds of children died in 2010 due to suspected lead poisoning from mining sources in Zamfara State among epidemiological concerns. Evaluating ecological and human health risks of heavy metals levels in sampled food crops harvested near two abandoned Lead-Zinc mining sites at Logo Benue State is crucial. Abelmoschus esculentus, Carica papaya, Manihot esculenta, and Zea mays were sampled, prepared, and analyzed for four heavy metals using the Atomic Absorption Spectrophotometric method. The mean data from the analysis of variance was subjected to ecological and health risk models. Pb means value ranged from Carica papaya Peel 0.46 ± 0.011 mg/kg to 1.30 ± 0.01 mg/kg in Zea mays seed. Zn was highest in Carica papaya flesh 0.50 ± 0.01 mg/kg, and lowest in Manihot esculenta peels and its flesh 0.12 ± 0.000 mg/kg. Hg and Cd were below detectable levels. Zea mays seeds (1.001) had the highest Pd bioaccumulation factor. BAF of zinc and ecological indices were <1. Daily Intake of Metals were all <1, however, Hazard Quotient (HQ) of Pb was ≥1 in Manihot esculenta flesh 1.143 and Zea mays at 1714. Cancer Risks were within permissible range (10-4 - 10-6). Health Risk result indicates communities around the mining area may be at risk of lead poisoning therefore due to high contamination of samples, routine checks on heavy metals especially lead is recommended to prevent excessive bioaccumulation in the body.

李凤珍主任医师从壮医毒虚论治痛风经验

“毒虚致病”是壮医学核心理论之一。李凤珍主任医师认为,“毒、虚”是痛风发病的关键因素,“湿、热、瘀”是其发病的关键环节,亦为病久之变。湿热瘀毒可阻滞龙路、火路,导致天地人三气不同步。她基于壮医“毒虚”理论论治痛风,认为痛风与脾肾两脏关系密切,应分期论治,急性发作期以“清热毒、除湿毒、消肿痛”为主,慢性缓解期以“健脾益肾、利湿化瘀”为主;根据痛风患者脾虚、肾虚及湿毒、瘀毒的主次,权衡用药,或以健脾益肾为主,或以利湿化瘀为主,多获良效。现整理成文,以期为痛风的防治提供诊疗思路及干预措施。

STUDY OF BEHAVIORAL TOXICOLOGY IN LEAD EXPOSED RATS

The study treated 72 s,rague-Dawley rats that were divided into 4 groups, one controlgroup and low, middle and higa dose groups, through drinking lead acetate solutions for threemonths. On the basis of founding subclinical lead poisoning model, behavioral toxicological testwhich consisted of neurobehavioral functions, neuroelectrophysiology and neurobiochemistry wascarried out. The results indicabo that low lvel lead exposure could result in the obvious changes orneurobehavioral function, neuroelectrophyslology and ueurobiochemistry, and the changes of neurobeltavioral runctiou had close correlatiom with P6B, Zap, NCV and DA, and they also had promlnant dose-response relatiouskips. The results suggested that the indexes of neurobehavioral functionmight be cousldered as early, semitive indexes for subolinical'lead poisoning. The combination ofneurobehavioral function with neuroectrophysiology could be used to evaluate the early neurotic toxicity of lead. The results also suggested that the change of dopamine metabolism of the central nervous system (CNS) might be one of the biological foundation of lead neurotic toxicity which changedthe neurobehavioral function of laboratory rats.

D-serine reduces memory impairment and neuronal damage induced by chronic lead exposure

Although exogenous D-serine has been applied as a neural regulatory intervention in many studies,the role played by D-serine in hippocampal injuries caused by lead exposure remains poorly understood.Rat models of chronic lead exposure were established through the administration of 0.05%lead acetate for 8 weeks.Simultaneously,rats were administered 30 or 60 mg/kg D-serine,intraperitoneally,twice a day.Our results showed that D-serine treatment shortened the escape latency from the Morris water maze,increased the number of times that mice crossed the original platform location,and alleviated the pathological damage experienced by hippocampal neurons in response to lead exposure.Although D-serine administration did not increase the expression levels of the N-methyl-D-aspartate receptor subtype 2B(NR2B)in the hippocampi of lead-exposed rats,60 mg/kg D-serine treatment restored the expression levels of NR2A,which are reduced by lead exposure.These findings suggested that D-serine can alleviate learning and memory impairments induced by lead exposure and that the underlying mechanism is associated with the increased expression of NR2A in the hippocampus.This study was approved by the Animal Ethics Committee of North China University of Science and Technology,China(approval No.LX2018155)on December 21,2018.

PREPARATION AND PROPERTIES OF CRYSTAL GLASSES WITHOUT LEAD CONTENT

BaO is the most common consideration in the preparation of newcrystal glass for getting rid of lead content in the glass andceramic wares to protect hu- man health and environment. But forkeeping the glass products' properties to meet the requirements ofthe tradi- tional crystal glass, B_2O_3, Al_2O_3, TiO_2, SrO and ZnOetc (at a special ratio) had been researched with BaO to con- stitutea mixture to replace the lead content in the glass compositions.