Humans ; Organometallic Compounds ; chemistry ; metabolism ; toxicity

Animals ; Humans ; Occupational Exposure ; Organometallic Compounds ; poisoning ; toxicity ; Rats ; Toxicity Tests

Animals ; Comet Assay ; DNA Damage ; drug effects ; Lymphocytes ; drug effects ; Male ; Organometallic Compounds ; toxicity ; Rats

The use of exogenous carbon monoxide releasing molecules (CORMs) provides promise for clinical application; however, the hazard potential of CORMs in vivo remains poorly understood. The developmental toxicity of CORM-3 was investigated by exposure to concentrations ranging from 6.25 to 400 μmol/L during 4-144 h post fertilization. Toxicity endpoints of mortality, spontaneous movement, heart rate, hatching rate, malformation, body length, and larval behavior were measured. CORM-3 disrupted the progression of zebrafish larval development at concentrations exceeding 50 μmol/L, resulting in embryonic developmental toxicity.
Animals ; Carbon Monoxide ; pharmacology ; Cardiotonic Agents ; toxicity ; Dose-Response Relationship, Drug ; Embryo, Nonmammalian ; drug effects ; Embryonic Development ; drug effects ; Organometallic Compounds ; toxicity ; Zebrafish ; embryology ; metabolism

OBJECTIVESTo study the effect of lead acetate on the expression of nerve growth factor (NGF) protein in rat brain and the regulation of thyroid hormone.

METHODSLead acetate was given to SD rats intraperitoneally ip. at the dosage of 25, 50 and 100 mg/kg respectively. 6-n-propyl-2-thiouracil (PTU) was used to make a hypothyroid model and then lead acetate was given at the dosage of 50 mg/kg body weight through i.p. The NGF protein expression in rat brain was observed by immunohistochemistry Triiodothyronine (T3), thyroxin (T4), TSH in serum and T3, T4 in brain tissue were determined by radio immunoassays (RIAs).

RESULTSThe average gray value of NGF protein in cerebral cortex of 50 mg, 100 mg treated groups (180.49 +/- 10.33, 169.72 +/- 19.75, respectively) were lower than the control (200.75 +/- 3.27, P<0.01). The area density of NGF protein in hippocampus of three treated groups (0.08 +/- 0.14, 0.12 +/- 0.02, 0.13 +/- 0.04, respectively) were significantly different from the control (0.025 +/- 0.015, P<0.05). The area density and the average gray value of NGF protein in lead acetate treated hypothyroid rat brain were of no significant changes. The levels of serum T3 in three treated groups [(0.68 +/- 0.02), (0.57 +/- 0.04), (0.54 +/- 0.02) microg/L respectively] and T4 [(28.30 +/- 1.83), (27.35 +/- 2.55), (24.00 +/- 3.01) microg/L] in serum were significantly lower while TSH [(6.34 +/- 1.13), (7.74 +/- 0.79), (9.16 +/- 0.77) IU] higher than those in the control [T3 (0.97 +/- 0.14) microg/L, T4 (54.50 +/- 3.70) microg/L and TSH (4.62 +/- 2.16) IU], and there was a good dose-response relationship. The levels of T3 in cerebral cortex of three treated groups [(13.26 +/- 0.81), (11.49 +/- 0.10), (10.42 +/- 1.19) pg/mg pro respectively] and T4 [(0.50 +/- 0.03), (0.49 +/- 0.13), (0.42 +/- 0.01) ng/mg pro] were significantly lower than those in control [(20.85 +/- 11.01) pg/mg pro, (0.76 +/- 0.14) ng/mg pro, P<0.05, P<0.01].

CONCLUSIONLead could increase the NGF protein expression in rat brain, which may be regulated by thyroid hormone.

Animals ; Brain Chemistry ; drug effects ; Immunohistochemistry ; Male ; Nerve Growth Factor ; analysis ; Organometallic Compounds ; toxicity ; Rats ; Rats, Sprague-Dawley ; Thyroid Hormones ; analysis ; blood ; physiology

OBJECTIVETo investigate the effect of lead exposure on copper and copper metalloenzyme and the intervention effect of quercetin.

METHODSTwenty-four specific pathogen-free male Sprague-Dawley rats of good health were randomly divided into control group (n = 8), lead acetate group (n = 8), and lead acetate + quercetin group (n = 8). The rats in lead acetate group were poisoned by drinking water with 1 g/L lead acetate for 8 weeks, while the rats in control group were fed by drinking water with sodium acetate of the same volume for 8 weeks; the rats in lead acetate+quercetin group were intraperitoneally injected with quercetin (30 mg × kg-1 × d-1) for 8 weeks while drinking water with lead acetate. The Morris water maze was used to test the learning and memory abilities of rats. The lead and copper levels in the serum, hippocampus, cortex, and bone were measured by graphite furnace atomic absorption spectrometry. The level of advanced glycation end products, activity of Cu/Zn superoxide dismutase (SOD), and content and activity of ceruloplasmin (CP) in the hippocampus and serum were measured using a test kit. HE staining was performed to observe the pathological changes in the hippocampus.

RESULTSThe Morris water maze test showed that the latency in lead acetate group (52.50±12.04 s) was significantly longer than that in control group (28.08±7.31 s) (P<0.05), and the number of platform crossings was significantly lower in the lead acetate group than in the control group. Compared with those in the control group, the lead levels in the cortex and hippocampus in lead acetate group increased 2.72-fold and 3.79-fold, and the copper in the cortex and hippocampus, and serum free copper levels in lead acetate group increased 1.15-fold, 1.48-fold, and 6.44-fold. Compared with the control group, the lead acetate group had a lower content of CP in the hippocampus (1.23±0.40 U/mg provs0.78±0.08 U/mg pro) and 31.81%and 19.49%decreases in CP content and Cu/Zn SOD activity. Free copper level in serum was positively correlated with the latency and lead levels in the serum, cortex, and hippocampus. The escape latency of rats in lead acetate + quercetin group was decreased by 42.15% (P<0.05). The lead levels in the cortex and hippocampus in lead acetate + quercetin group (0.246 ± 0.58 µg/g and 0.202±0.049 µg/g) were significantly lower than those in lead acetate group (0.391±0.49 µg/g and 0.546±0.120 µg/g), but the free copper and copper levels in the hippocampus and cortex were not significantly reduced. The lead acetate + quercetin group had higher Cu/Zn SOD activity and CP content in the hippocampus than the lead acetate group (P < 0.05). The light microscope observation showed that the number of cells in the hippocampus was reduced with disordered arrangement in the lead acetate group; with quercetin intervention, the hippocampus damage was reduced.

CONCLUSIONLead exposure results in disorder of copper homeostasis, while quercetin may alleviate the damage induced by lead to some extent.

Animals ; Cerebral Cortex ; chemistry ; Copper ; blood ; Hippocampus ; chemistry ; Homeostasis ; Learning ; drug effects ; Male ; Memory ; drug effects ; Organometallic Compounds ; toxicity ; Quercetin ; pharmacology ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVEChronic lead (Pb) exposure during development is known to produce learning deficits. Nitric oxide participates in the synaptic mechanisms involved in certain forms of learning and memory. This study was designed to clarify whether Pb-induced impairment in learning and memory was associated with the changes of nitric oxide levels in mice brains.

METHODSSixty Balb/c mice aged 10 days were chosen. A model of lead exposure was established by drinking 0.025%, 0.05%, 0.075% lead acetate, respectively for 8 weeks. The controls were orally given distilled water. The ability to learn and memorize was examined by open field test, T-water maze test. In parallel with the behavioral data, NO level of hippocampus tissue was detected by biochemical assay.

RESULTSCompared with control groups, (1) the weight of 0.075% group was significantly reduced (P<0.05); (2) The number of times in mice attaining the required standards in T-water maze test was lower in 0.075% group (P<0.01). No significant difference was found between experimental and control groups in open field test (P>0.05); (3) NO level of mouse hippocampus tissue was decreased in 0.075% group (P<0.01).

CONCLUSIONSThe findings suggest that decreased hippocampus NO level may contribute to the Pb-induced deficits in learning and memory processes.

Animals ; Dose-Response Relationship, Drug ; Hippocampus ; drug effects ; metabolism ; Memory ; drug effects ; physiology ; Mice ; Mice, Inbred BALB C ; Nitric Oxide ; metabolism ; Organometallic Compounds ; toxicity ; Weight Loss

OBJECTIVETo explore the toxic effects of lead acetate on the apoptosis and ultrastructure of human renal tubular epithelial cells (HK-2).

METHODSAfter HK-2 cells were exposed to 5, 10 and 20 µmol/L lead acetate for 24 h, the morphological changes of HK-2 cells were observed by Hochest 33342-PI staining, and the ultrastructure changes of HK-2 cells were examined under a electron microscope, LDH activity and MDA content in supernatant of HK-2 cellular culture were detected by spectrophotometer, DNA damage of HK-2 was determined by DNA ladder and the apoptotic rates of HK-2 cells were measured by flow cytometry.

RESULTSThe morphological changes of apoptotic HK-2 cells in exposure group were observed by Hochest 33342-PI staining. The cytoplasm vacuoles, karyopycnosis, nuclear membrane vague and apoptotic bodies in HK-2 cells of exposure group were found under electron microscopy. LDH activity and MDA contents in exposure group increased significantly, as compared to control group (P < 0.01). The results of DNA Ladder showed that DNA damage of HK-2 cells in exposure group appeared. The apoptotic rates of HK-2 cells exposed to 5, 10, 20 µmol/L lead acetate were 14.16% ± 2.94%, 19.45% ± 2.73%, 25.01% ± 3.97%, respectively, which were significantly higher than that (5.81% ± 2.18%) in control group (P < 0.05).

CONCLUSIONLead acetate could remarkably induce the apoptosis of HK-2 cells and affect the kidney.

Apoptosis ; drug effects ; Cell Line ; Epithelial Cells ; cytology ; drug effects ; ultrastructure ; Humans ; Kidney Tubules, Proximal ; cytology ; drug effects ; ultrastructure ; Organometallic Compounds ; toxicity

OBJECTIVETo evaluate the effect of different doses of lead acetate (1/20, 1/40 and 1/60 of LD50) on body weight gain, blood picture, plasma protein profile and the function of liver, kidney and thyroid gland.

METHODSMale albino rats were divided into four groups, the first group represented the health control animals, while the second, third and fourth groups were ingested orally with sub lethal doses of lead acetate (1/20, 1/40 and 1/60) of the oral LD50, respectively. One dose was ingested every two days during the experimental period (14 weeks) including the adaptation time. Blood was collected and used for all analysis.

RESULTSThe results showed that, the ingestion of Pb(2+) induced significant stimulation in glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminease (AST) activity. Also, total soluble protein and albumin contents of plasma were significantly decreased, while the content of globulin was changed by the Pb(2+) treatments. The cholinesterase activity was inhibited, but the activities of alkaline and acid phosphates and lactate dehydrogenase were stimulated, while plasma glucose level was elevated as a result of lead acetate intoxication. In case of blood picture, Pb(2+) ingestion reduced the contents of hemoglobin and RBCs count of intoxicated rat's blood and the plasma levels of T3, T4 and blood WBCs count were decreased.

CONCLUSIONSIt can be concluded that lead acetate has harmful effect on experimental male albino rats. Therefore, the present work advises people to prevent exposure to the lead compound to avoid injurious hazard risk.

Animals ; Blood Cells ; Blood Chemical Analysis ; Kidney Function Tests ; Lead Poisoning ; pathology ; physiopathology ; Liver Function Tests ; Male ; Organometallic Compounds ; toxicity ; Rats, Sprague-Dawley ; Thyroid Function Tests

OBJECTIVETo investigate the effects of lead exposure on the copper concentration in the brain and serum and the expression of copper transporters in the choroid plexus among rats.

METHODSSixty specific pathogen-free Sprague-Dawley rats were randomly divided into a control group and three lead-exposed groups, with 8 mice in each group. The lead-exposed groups were orally administrated with 500 (low-dose group)), 1 000 (middle-dose group), and 2 000 mg/L (high-dose group) lead acetate in drinking water for eight weeks. And the rats in control group were given 2 000 mg/L sodium acetate in drinking water. The content of lead and copper in the serum, hippocampus, cortex, choroid plexus, bones, and cerebrospinal fluid (CSF) was determined by inductively coupled plasma-mass spectrometry (ICP-MS). Confocal and real-time PCR methods were applied to measure the expression of copper transporters including copper transporter 1 (Ctr1), antioxidant protein 1 (ATX1), and Cu ATPase (ATP7A).

RESULTSCompared with the control group, the lead-exposed groups showed significantly higher lead concentrations in the serum, cortex, hippocampus, choroid plexus, CSF, and bones (P < 0.05) and significantly higher copper concentrations in the CSF, choroid plexus, serum, and hippocampus (P < 0.05). Confocal images showed that Ctr1 protein was expressed in the cytoplasm and cell membrane of choroid plexus in control group. However, Ctr1 migrated to CSF surface microvilli after lead exposure. Ctr1 fluorescence intensity gradually increased with increasing dose of lead, except that the middle-dose group had a higher Ctr1 fluorescence intensity than the high-dose group. In addition, the middle- and high-dose groups showed a lower ATX1 fluorescence intensity compared with the control group. Real-time PCR data indicated that the three lead-exposed groups showed significantly higher mRNA levels of Ctr1 and ATP7A compared with the control group (P < 0.05).

CONCLUSIONCopper homeostasis in the choroid plexus is affected by lead exposure to induce copper homeostasis disorders in brain tissue, which may be one of the mechanisms of lead neurotoxicity.

Adenosine Triphosphatases ; Animals ; Brain ; Cation Transport Proteins ; drug effects ; Choroid Plexus ; drug effects ; metabolism ; Copper ; metabolism ; Homeostasis ; Organometallic Compounds ; toxicity ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley