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

OBJECTIVETo observe the effects of prenatal exposure to lead on nephroblastoma over-expressed gene (NOV) protein and mRNA expression in hippocampus of rats' offspring, and to explore the molecular mechanism of lead on learning and memory.

METHODSThe pregnant rats were divided into 1 control group and 3 lead expose groups randomly: low( 125 mg/L), middle (250 mg/L) and high (500 mg/L). 8 rats in each group. From pregnancy ld until birth, the rats were given double evaporated water or lead acetate water of different doses according to their groups. The samples of descendants were taken on embryo 18 th day, postnatal 1st day, 21st day, 60th day. The contents of lead in blood and hippocampus were determined by hydride generation atomic absorption spectrometry method. The expression of NOV protein and mRNA in hippocampus were observed by immunohistochemistry and in situ hybridization.

RESULTSThe lead contents of blood [(312.46 +/- 43.55), (419.35 +/- 62.25), (541.45 +/- 47.90) microg/L] and hippocampus[(2.10 +/- 0.18), (2.58 +/- 0.12), (3.41 +/- 0.23) microg/L] were significantly higher in lead exposed groups than that of control [(214.31 +/- 40.77), (0.76 +/- 0.13) microg/L] (P < 0.05) on the embryo 18th, 1st and 21 st day, while there was no significantly difference among them on 60 th day. The expression of NOV protein in all lead exposed groups were significantly decreased compared with control group (P < 0.05) on 1st and 21 st day, while there was no significantly difference among them on 60th day. The expression of NOV mRNA of all the lead exposed groups were significantly decreased compared with control group (P < 0.05) on the embryo 18th, 1st and 21st day, while there was significantly difference only in the high dose group (0.0355 +/- 0.0100) compared with control (0.0900 +/- 0.0200) (P < 0.01) on 60th day.

CONCLUSIONPregnancy low level lead exposure could decrease the NOV protein and mRNA expression in hippocampus of offspring, which might be one of the molecular mechanisms of effect of lead on learning and memory.

Animals ; Female ; Gene Expression ; Hippocampus ; metabolism ; Lead ; adverse effects ; blood ; Nephroblastoma Overexpressed Protein ; genetics ; metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

Diseases of the peripheral nervous system are the most prevalent in patients with end-stage renal disease (ESRD). Although increased blood levels of lead in ESRD have been reported, the role of lead remains to be elucidated. The purpose of this study was to determine the connection of blood lead concentration with peripheral nerve conduction velocity. One hundred ninety-eight healthy subjects (control group) and 68 patients with ESRD undergoing hemodialysis (ESRD group) were enrolled. Nerve conduction was measured within two hours after hemodialysis. Orthodromic sensory nerve action potentials and compound muscle action potentials were recorded on the median, ulnar, and radial nerves. Hemoglobin-corrected blood lead was significantly higher in ESRD patients than in controls (9.1+/-2.8 microgram/dL vs. 5.9+/-2.3 microgram/dL, p<0.001). 32.4% of 68 ESRD patients with diabetes mellitus were significantly related to poorer motor and sensory nerve conduction velocity (p<0.001). However, blood lead was not a significant predictor of the nerve conduction velocity (p>0.05). Our result suggested that even though the blood lead levels were high in ESRD, they were not associated with the decline of peripheral nerve function. Diabetes mellitus is a primary independent risk of neuropathy in ESRD patients.
Peripheral Nervous System Diseases/blood/etiology/physiopathology ; Peripheral Nerves/physiopathology ; Neural Conduction/*physiology ; Middle Aged ; Male ; Lead/*blood/metabolism ; Kidney Failure, Chronic/*blood/complications/*physiopathology ; Humans ; Female ; Diabetic Neuropathies/blood/physiopathology ; Case-Control Studies ; Bone and Bones/metabolism ; Body Burden ; Adult

OBJECTIVETo observe the effect of vitamin C and E on blood lead (Pb) levels and SOD, GSH-Px, NOS activity and NO, MDA content in hippocampus of rats with lead poisoning.

METHODSRat lead poisoning model was established by oral administration of 0.615 mmol/L lead acetate in drinking water for 4 weeks; and animals were fed with vitamin C 100 mg/kg. bw and/or vitamin E 100 mg/kg. bw for 1 week. Then blood Pb levels and SOD, GSH-Px, NOS activity and MDA, NO contents in hippocampus of rats were determined by corresponding kits.

RESULTCompared with control group, blood Pb level was decreased significantly (P<0.05) after given vitamin C, vitamin E or combination of vitamin C and E. The concentrations of SOD, GSH-Px, NO and NOS were significantly higher in vitamin C and/or E groups than those in control group (P<0.05). The concentration of MDA in vitamin treatment groups was significantly lower than that in lead control group (P<0.05); furthermore concentration of MDA in combination of vitamin C and E group was significantly higher than that in vitamin C alone group (P<0.05).

CONCLUSIONAdministration of vitamin C and E can decrease blood lead level, alleviate damage of lipid peroxidation in hippocampus by lead toxicity and reverse NO, NOS levels in rats with lead poisoning.

Animals ; Antioxidants ; pharmacology ; therapeutic use ; Ascorbic Acid ; pharmacology ; therapeutic use ; Glutathione Peroxidase ; metabolism ; Hippocampus ; metabolism ; Lead ; blood ; Lead Poisoning ; drug therapy ; metabolism ; Lipid Peroxidation ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Vitamin E ; pharmacology ; therapeutic use

Adult ; Aged ; Aged, 80 and over ; Environmental Pollutants ; Female ; Genotype ; Humans ; Lead ; blood ; Male ; Middle Aged ; Occupational Exposure ; Polymorphism, Genetic ; RNA, Long Noncoding ; genetics ; metabolism ; Risk Factors ; Young Adult

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

OBJECTIVETo study the effects of low pre-pregnant lead exposure level on the mobilization of lead and calcium in maternal skeleton during gestation and lactation in mice.

METHODSSeventy Kunming female mice were randomly divided into the lead exposure or control groups, 36 mice were exposed to lead by drinking water (50 mg/L) and 36 mice were exposed to deionized water for 4 weeks. The levels of calcium and lead in blood and femurs were measured on the 1st, 7th and 14th days during gestation and on the 1st,10th and 21st days during lactation with atomic absorption spectrophotometry using a heated graphite atomizer or flame atomic absorption spectrophotometry.

RESULTSAs compared with the pre-pregnant, at the end of lactation in exposure group the levels of calcium in blood and bones significantly decreased 18.5% and 17.75%, respectively, the levels of lead in blood significantly increased 65.22% and the levels of lead in bones significantly decreased 28.45% (P < 0.05). There was a significant negative correlation between the blood lead level and the bone lead level during gestation and lactation in exposure group (r = -0.904, P < 0.01). There were significant differences of lead and calcium levels during the gestation and lactation between exposure group and control group (P < 0.05).

CONCLUSIONThe lead mobilization in maternal bone occurred during gestation and lactation in mice, which could be accelerated by the low pre-pregnant lead exposure.

Animals ; Bone Remodeling ; drug effects ; Bone and Bones ; drug effects ; metabolism ; Calcium ; blood ; metabolism ; Calcium, Dietary ; Female ; Lactation ; Lead ; blood ; toxicity ; Mice ; Mice, Inbred Strains ; Pregnancy ; Prenatal Exposure Delayed Effects

OBJECTIVETo observe the effect of long-term external use of Goupi Gao on renal function and lead accumulation in rats.

METHODRats were externally administered with Goupi Gao at different doses (7, 3.5 and 1.75 g x kg(-1)) for 90 d. At 45 days and 90 days after administration, the renal indicator, levels of blood urea nitrogen (BU) and creatinine (Cr) in serum, beta2-microglobulin (beta2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) in urine were determined. Lead content in kidneys was detected by atomic absorption spectrometry.

RESULTA 90-day administration with Goupi Gao significantly enhanced the renal indicator, levels of NAG in urine and lead content in renal, when compared with the normal rats. However, the levels of BUN and beta2-MG as well as renal pathology in Goupi Gao treated rats were not obviously changed.

CONCLUSIONConsecutive administration of Goupi Gao for 90 days can increase the renal indicator and levels of NAG in urine, enhance the accumulation of lead in renal, but with no effect on excretory function of kidneys and organic changes.

Acetylglucosaminidase ; urine ; Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Female ; Kidney ; drug effects ; metabolism ; pathology ; Lead ; analysis ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrophotometry, Atomic ; beta 2-Microglobulin ; urine

OBJECTIVETo investigate the effects of occupational lead exposure on the bone mineral density and the bone metabolism in exposed workers.

METHODSTwo hundred and ninety-eight lead-exposed workers in a storage battery plant in Shanghai were selected as the exposed subjects while eighty-one healthy officers in the plant who were not occupationally exposed to lead were treated as the control. The blood lead (BPb) and the urinary lead (UPb) were used as the exposure biomarkers while the Z score, the urinary hydroxyproline (HYP) the serum alkaline phosphatase (ALP) the serum alkaline phosphatase bone isoenzyme BALP and the serum osteocalcin BGP were used as the effect biomarkers for the bone effect caused by the lead. Bone mineral density (BMD) was measured by the single-photon absorptiometry (SPA-4).

RESULTSThe BPb, UPb, HYP, ALP, BALP in the occupational lead exposure group were higher than those in the control group with significantly statistical difference in male (P < 0.01). The levels of BGP in the exposure group was higher than that in the control group without significantly statistical difference (P > 0.05). The BMD in the exposure group was lower than that in the control group without significantly statistical difference (P > 0.05). The BMD was significantly decreased in the groups of the UPb 10 approximately microg/g Cr level compared with the 0 approximately microg/g Cr group with the significant difference (P < 0.01). In males, the BMD was significantly decreased in the group of the BPb 300 approximately microg/L level compared with the 0 approximately microg/L group with the significant difference (P < 0.01). The levels of HYP, ALP, BALP, BGP in the UPb 20 approximately microg/g Cr group were significantly higher than those in the UPb 0 approximately microg/g Cr group (P < 0.05). The levels of HYP, ALP, BALP, BGP in the BPb 300 approximately microg/L group were significantly higher than those in the BPb 0 approximately microg/L group (P < 0.05). The prevalence of both osteoporosis and the abnormal bone metabolisms indexes would increase significantly with the increase of the lead exposure (P < 0.01) with the linear correlation (P < 0.01). But the prevalence of higher BGP had no significant correlation with UPb (P > 0.05). BMDs were calculated using BMDS Version 1.3.2 software and BMDLs were also determined. The BMDLs of BPb and UPb for lead-induced osteoporosis were higher than those representing the change of bone metabolism induced by lead.

CONCLUSIONSThe occupational exposure to lead could cause the decrease of the bone mineral density, lead to the osteoporosis, and may affect the bone metabolism.

Adult ; Aged ; Biomarkers ; blood ; urine ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; metabolism ; Case-Control Studies ; Female ; Humans ; Lead ; adverse effects ; blood ; urine ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Osteoporosis ; chemically induced ; Young Adult

OBJECTIVETo investigate antagonism effects of total flavonoids from Chrysanthemum morifolium. (TFCM) against lead induced oxidative injury.

METHODNinety male mice were randomly divided into 9 groups. Mice except normal control group inject lead acetate every other day for 20 days. In the next 10 d, drugs were orally administrated to mice once a day. After the last aministration, mice were sacrificed and immediately subjected to necropsy. The concentration of lead, zinc and copper in blood, brain, liver and kidney were determined. The body weight, relative organ weight, antioxidant enzyme levels (GSH, GSH-Px, SOD and CAT) and lipid peroxidation products (MDA) were performed.

RESULTTFCM might antagonize the decrease of body weight and the increase of organ weight/body weight ratio. The combined treatment with TFCM and DMSA can significantly lower the lead levels in blood, brain, liver and kidney. In contrast, lead concentration in mice treated with TFCM alone did not show significant change in these organs. The other trace elements such as zinc and copper had no significant decrease after TFCM or DMSA treatment. Middle and high-dose TFCM was more effective than DMSA in increasing the activity of GSH, GSH-Px, SOD, CAT and decreasing the concentration of MDA in mice brain. In addition, high-dose TFCM was more effective than DMSA in increasing the activity of GSH-Px, CAT and decreasing the concentration of MDA in mice liver and kidney. The combined treatment with TFCM and DMSA also can reverse lipid peroxidation and increase antioxidant enzyme levels in lead poisoning mice dose-dependently, and it had more beneficial effects than treatment with DMSA alone.

CONCLUSIONTFCM might improve antioxidant defense system, reverse lipid peroxidation and protect brain, liver and kidney against lead induced oxidative damage in mice significantly.

Administration, Oral ; Animals ; Brain ; drug effects ; metabolism ; Chrysanthemum ; chemistry ; Copper ; blood ; metabolism ; Drug Antagonism ; Flavonoids ; administration & dosage ; chemistry ; Kidney ; drug effects ; metabolism ; Lead ; blood ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Oxidative Stress ; drug effects ; Random Allocation ; Succimer ; administration & dosage ; Zinc ; blood ; metabolism