OBJECTIVES: To determine the neuroprotective effects of berberine hydrochloride (BBR) against lead-induced injuries on the hippocampus of rats. METHODS: Wistar rats were exposed orally to doses of 100 and 500 ppm lead acetate for 1 and 2 months to develop subchronic and chronic lead poisening models, respectively. For treatment, BBR (50 mg/kg daily) was injected intraperitoneally to rats poisoned with lead. At the end of the experiment, the spatial learning and memory of rats were assessed using the Morris water maze test. Hippocampal tissue changes were examined by hematoxylin and eosin staining. The activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels as parameters of oxidative stress and antioxidant status of the hippocampus were evaluated. RESULTS: BBR reduced cognitive impairment in rats exposed to lead (P<0.05 or P<0.01). The resulting biochemical changes included a decrease in the activity of antioxidants and an increase in lipid peroxidation of the hippocampus of lead-exposed rats (P<0.05 or P<0.01), which were significantly modified by BBR (P<0.05). BBR also increased the density of healthy cells in the hippocampus of leadexposed rats (P<0.05). Significant changes in tissue morphology and biochemical factors of the hippocampus were observed in rats that received lead for 2 months (P<0.05). Most of these changes were insignificant in rats that received lead for 1 month. CONCLUSION BBR can improve oxidative tissue changes and hippocampal dysfunction in lead-exposed rats, which may be due to the strong antioxidant potential of BBR.
Animals ; Hippocampus/pathology* ; Rats, Wistar ; Antioxidants/pharmacology* ; Berberine/therapeutic use* ; Cognition/drug effects* ; Male ; Lead Poisoning/metabolism* ; Chronic Disease ; Oxidative Stress/drug effects* ; Maze Learning/drug effects* ; Rats ; Lipid Peroxidation/drug effects* ; Malondialdehyde/metabolism*

A 61-year-old male patient was admitted because of unexplained abdominal pain and anemia. His past medical history was unremarkable except for having taken herbal medicine to treat facial palsy two months ago. The result of health examination performed about a month ago showed increased serum aspartate and alanine aminotransferase level, and he was diagnosed with toxic hepatitis by herbal medicine. When the patient presented to the outpatient department three weeks ago, follow-up liver function test results showed improvement but he complained of abdominal pain. Despite extensive blood chemistry tests and computed tomography, the cause of pain could not be found. After much deliberation, serum lead level and herbal medicines analysis was performed based on the fact that he took herbal medicine two months ago, and he could finally be diagnosed with lead poisoning. Since the serum lead level was high enough to be indicated for lead chelating therapy, conservative management was given. When a patient with toxic hepatitis due to herbal medication presents with abdominal pain, the possibility of lead poisoning should always be taken into consideration.
Acute Disease ; Alanine Transaminase/analysis ; Aspartate Aminotransferases/analysis ; Chemical and Drug Induced Liver Injury/*diagnosis ; Hemoglobins/analysis ; Humans ; Lead/analysis ; *Lead Poisoning ; Liver/enzymology/metabolism ; Liver Function Tests ; Male ; Middle Aged ; Plants, Medicinal/chemistry

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, Parkinsons 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.
Alzheimer Disease ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Animals ; Behavior ; drug effects ; Biomarkers ; metabolism ; Brain ; metabolism ; pathology ; physiopathology ; Brain Diseases ; chemically induced ; pathology ; physiopathology ; Environmental Exposure ; adverse effects ; Humans ; Lead ; pharmacokinetics ; toxicity ; Lead Poisoning ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Neurotoxicity Syndromes ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Schizophrenia ; chemically induced ; metabolism ; pathology ; physiopathology

A study of amoxicillin pharmacokinetics was conducted in healthy goats and goats with chronic lead intoxication. The intoxicated goats had increased serum concentrations of liver enzymes (alanine aminotransferase and gamma-glutamyl transferase), blood urea nitrogen, and reactivated delta-aminolevulinic acid dehydratase compared to the controls. Following intravenous amoxicillin (10 mg/kg bw) in control and lead-intoxicated goats, elimination half-lives were 4.14 and 1.26 h, respectively. The volumes of distribution based on the terminal phase were 1.19 and 0.38 L/kg, respectively, and those at steady-state were 0.54 and 0.18 L/kg, respectively. After intramuscular (IM) amoxicillin (10 mg/kg bw) in lead-intoxicated goats and control animals, the absorption, distribution, and elimination of the drug were more rapid in lead-intoxicated goats than the controls. Peak serum concentrations of 21.89 and 12.19 microg/mL were achieved at 1 h and 2 h, respectively, in lead-intoxicated and control goats. Amoxicillin bioavailability in the lead-intoxicated goats decreased 20% compared to the controls. After amoxicillin, more of the drug was excreted in the urine from lead-intoxicated goats than the controls. Our results suggested that lead intoxication in goats increases the rate of amoxicillin absorption after IM administration and distribution and elimination. Thus, lead intoxication may impair the therapeutic effectiveness of amoxicillin.
Amoxicillin/blood/*pharmacokinetics/urine ; Animals ; Anti-Bacterial Agents/blood/*pharmacokinetics/urine ; Area Under Curve ; Chromatography, High Pressure Liquid/veterinary ; Goat Diseases/*chemically induced/metabolism ; Goats ; Half-Life ; Injections, Intramuscular/veterinary ; Injections, Intravenous/veterinary ; Lead Poisoning/etiology/metabolism/*veterinary ; Male

OBJECTIVEIn order to study the feature of T cell TCR-CD3 complex-mediated gene in lead poisoning patients.

METHODSReal-time PCR with SYBR Green I technique was used for determination of the expression levels of CD3 genes in peripheral blood mononuclear cells of 46 cases lead poisoning patients (11 cases in observation group and 35 cases in mild lead poisoning group) and 31 cases in control group.

RESULTSThe median expression levels of CD3γ gene in observation group and mild lead poisoning group (6.89%, 5.87 %) were higher than the control group (P < 0.05). The median expression levels of CD3δ gene in observation group and mild lead poisoning group (0.54%, 0.70%) were lower than the control group (P < 0.05). The median expression levels of CD3ε gene in observation group and mild lead poisoning group (10.22%, 6.08%) were higher than the control group (P < 0.05). A significant Positive correlation was found between CD3γ, CD3ε and seniority in lead poisoning patients. A significant negative correlation was found between CD3ε and blood ZPP, urea δ-ALA (r = -0.358, P < 0.05; r = -0.385, P < 0.05), but there was no significant correlation between them after controlling for blood lead, urea lead. The expression levels of CD3 genes prove to be a descending order of CD3γ, CD3ε, CD3δ in control group, while it was changed for CD3ε, CD3γ, CD3δ in the observation group as well as in mild lead poisoning group.

CONCLUSIONExpression of T cell TCR-CD3 complex-mediated gene was changed in lead poisoning patients, it might be related to the body immunodeficiency. The expression level of CD3ε gene can be used as sensitive immune function screening indicator in Lead poisoning patients.

Adolescent ; Adult ; Aged ; Female ; Humans ; Lead Poisoning ; immunology ; Male ; Occupational Diseases ; immunology ; Receptor-CD3 Complex, Antigen, T-Cell ; metabolism ; Young Adult

Animals ; Brain ; drug effects ; Female ; Lead Poisoning ; Lipid Peroxidation ; Male ; Mice ; Mice, Inbred ICR ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the effects of chronic lead exposure on expression of autophagy-associated proteins in rat hippocampus.

METHODSSD rats were randomly divided into three groups: control group was given distilled water, lead-exposed groups were given 0.5 g/L (low-dose) or 2.0 g/L(high-dose) lead acetate solution in drinking water. The rat pups started to drink the lead content water until 60 d maturity. The lead contents in blood and brain samples were analyzed by graphite furnace atomic absorption spectrophotometry. The expressions of Beclin 1, LC3, LAMP2 and cathepsin B proteins were detected by Western blot and immunohistochemistry.

RESULTSCompared with control group, the contents of lead were significantly higher in blood and hippocampus samples in chronic lead-exposed rats (P<0.01). Western blot showed that the expression of Beclin 1 and LC3-II/LC3-I increased significantly in high dose lead-exposed group compared with control group (P<0.05 or P<0.001). The confocal laser immunostaining results demonstrated that increased immunofluorescence staining of cathepsin B in hippocampal neurons compared with control animals.

CONCLUSIONThe disturbance of autophagy-lysosome signaling molecules might be partially contribute to neurotoxicity of chronic lead exposure.

Animals ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; drug effects ; physiology ; Beclin-1 ; Cathepsin B ; metabolism ; Chronic Disease ; Disease Models, Animal ; Female ; Hippocampus ; drug effects ; metabolism ; pathology ; Lead Poisoning ; metabolism ; pathology ; Lysosomal-Associated Membrane Protein 2 ; metabolism ; Male ; Microtubule-Associated Proteins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects

OBJECTIVETo investigate the effect of potassium iodide on the expression of nuclear factor-kappaB and fibronectin.

METHODSThe experiment was performed with 72 SD rats weighing about 180-220 g. The animals were randomly assigned into nine groups. Group A, B, C (n=8) served as control and were fed with distilled water for 1 month, 2 month, 3 month respectively. Group D, E, F (n=8) served as lead exposed and were fed with water with 0.5% lead acetate for 1 month, 2 month, 3 month respectively. Group G, H, I (n=8) served as potassium iodide and lead exposed and were treated with 0.5% lead acetate simultaneously taking potassium iodide 3 mg/100 g weight by intragastric administration for 1 month, 2 month, 3 month respectively. Animals of different groups were sacrificed at the end of the treatment. Ultrastructure of kidney was observed by electron microscopy; Expression of NF-kappaB and FN protein and mRNA in kidney were measured respectively by immunohistochemistry and RT-PCR.

RESULTSElectron microscopic examination revealed potassium iodide could restrain the denaturalization in epithelial cells and mitochondrial cristae. The expressions of NF-kappaB protein (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839) and mRNA (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538) in all the lead exposed groups continuously increased compared with correspondent control groups; Group I was decreased obviously compared with group F. The expressions of FN protein (0.4243 +/- 0.0595, 0.4917 +/- 0.0891) and mRNA (0.8650 +/- 0.0880, 0.8714 +/- 0.0980) in group E and F increased compared with group B and C, but the expressions of FN protein in group I significantly decreased compared with group F; The expressions of FN mRNA in Group H and I significantly decreased compared with group E and F.

CONCLUSIONThe potassium iodide can ameliorate renal ultrastructure and degrade expression of nuclear factor-kappaB and fibronectin induced by lead.

Animals ; Disease Models, Animal ; Fibronectins ; genetics ; metabolism ; Kidney ; drug effects ; metabolism ; ultrastructure ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Lead Poisoning ; complications ; metabolism ; pathology ; Male ; NF-kappa B ; genetics ; metabolism ; Potassium Iodide ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo understand the effects of moderate lead poisoning on the hippocampus tissue of rabbits in juvenile stage.

METHODSSixteen 45-day-old male New Zealand rabbits were randomly divided into blank group and lead-exposed group,8 for each group. Rabbits in the lead-exposed group were treated with 5 mg x kg(-1) x d(-1) lead acetate in their forage for 6 weeks to establish a moderate lead poisoning animal model. The blood lead levels and the lead contents in the hippocampus were determined by atomic absorption spectrometer and inductively coupled plasma-mass spectrometry respectively. Histopathology and ultra-microstructure in the hippocampus tissue were observed by light microscope and electron microscope. The NR1, NR2A and NR2B protein expressions in the CA1 hippocampal region were analyzed through immunohistochemical method.

RESULTSCompared with those of blank group, the blood lead levels of lead-exposed group were significant increased, (428.63 +/- 9.46) vs (66.38+/-3.93) microg/L (t = 100.08, P<0.01); and lead contents of hippocampus was significantly increased, (44.57+/-2.03) vs (21.20+/-1.53) ng/g, (t = 26.05, P<0.01); the hippocampus wet weight were significant decreased, (0.735 +/-0.012) vs (0.808+/-0.010), (t =12.97, P<0.01); the coefficient of hippocampus wet weight, was (0.458 +/-0.004) vs (0.476+/-0.005), (t =7.87, P<0.01). The significant declines in both the positive rate of NR1 and NR2A in the CA1 hippocampal region for NR1: (37.44 +/- 2.05)% vs (41.81+/-2.50)% (t = 3.82, P<0.01) and for NR2A: 21.97+/-1.08 vs 25.48+/-1.30 (t =5.89, P<0.01) were also observed. With light microscope and electron microscope, the histopathology and ultra-microstructure of neuron and glial cell in the hippocampus tissue were changed.

CONCLUSIONThe impairment of hippocampus of rabbits in juvenile stage with chronic moderate lead poisoning were observed, and the histopathology and N-methyl-D-aspartate receptor protein expressions in the hippocampus tissue were changed.

Animals ; Chronic Disease ; Disease Models, Animal ; Hippocampus ; drug effects ; metabolism ; pathology ; Lead Poisoning ; metabolism ; Male ; Rabbits ; Receptors, N-Methyl-D-Aspartate ; metabolism

OBJECTIVETo explore the effects of S-adenosyl-L-methionine (SAM) on blood lead concentration and oxidative stress of tissue in prenatal and postnatal lead-exposed rats, and evaluate the potential reparation exerted by SAM on paired-pulse facilitation (PPF) and long-term potentiation (LTP) in lead-exposed rat.

METHODSPregnant Wistar rats were randomly divided into three groups: control, lead-exposed and lead-exposed with SAM treatment groups. Lead-exposed rats drank 1.5 g/L lead acetate solution through pregnancy until weaning and then the pups received 20 mg/kg SAM or saline daily intraperitoneally depending on their group. Control group rats drank tap water throughout the experiment. At the postnatal 44-60 days, all the pup rats were given an extracellular recording measured in dentate gyrus (DG) area of hippocampus. The blood lead concentration and oxidative stress in liver, brain and hippocampus were also detected.

RESULTSThe blood lead concentration in lead-exposed group was higher (159. 3 +/- 10. 9 microg/L) in comparing with those of control group (27.5 +/-3.8 microg/L) and lead +SAM group (33.1 +/-9.5 microg/L) (F=213.5, P<0.01). A significant recovery of liver, brain glutathione (GSH) and malondialdehyde (MDA) level was clearly produced in lead-exposed rats after SAM treatment (P <0.05). Chronic lead exposure during development impaired LTP measured on field excitatory postsynaptic potential (EPSP) [(112 +/-2.1)%] compared with control rats [(131+/-4.5)%] and the impaired LTP could be significantly increased by SAM treatment [(120 +/- 2.6)%] (F = 26. 1, P <0. 05).

CONCLUSIONSAM might be beneficial for treatment of lead intoxication, especially in the rescue of learning and memory impairment induced by lead and should deserve more detailed research.

Animals ; Brain ; metabolism ; Female ; Glutathione ; biosynthesis ; Lead ; blood ; Lead Poisoning ; prevention & control ; Long-Term Potentiation ; drug effects ; Male ; Maternal Exposure ; prevention & control ; Pregnancy ; Rats ; Rats, Wistar ; S-Adenosylmethionine ; pharmacology