Humans ; Organometallic Compounds ; chemistry ; metabolism ; toxicity

Animals ; Manganese ; chemistry ; Molecular Structure ; Organometallic Compounds ; chemical synthesis ; chemistry ; Superoxide Dismutase ; chemistry ; metabolism

Our work focuses on the quality control and structural identification of Photocyanine as a cancer therapeutic photosensitizer. Photocyanine is a mixture which contains four ZnPcS2P2 type substituted Phthalocyanine isomers. In order to obtain the single component from Photocyanine, the mixture of four isomers possessing the similar structures and chemical property had been isolated and purified. An HPLC method with a mixture of methanol-acetonitrile-ion-pair buffer as the mobile phase was applied to isolate the four isomers by means of a semi-preparative C18 column. To remove the salts which were mixed in the preparative product, a SPE C18 column was used to separate the salts by elution with water and then the marker component was eluted by methanol. Subsequently, a column of Sephadex LH-20 gel was applied to elute the crudes with methanol to desalination. The purity of the isolated compound was measured by TLC and four different isomers of phthalocyanine were obtained. The chemical structures of them were elucidated by 1H NMR spectra, gCOSY and NOE1D. An HPLC-DAD method was developed for simultaneously determination of four major isomers in Photocyanine with a C18 column (Grace Smart, 150 mm x 4.6 mm ID, 5 microm). The separation was carried out with a gradient program at a flow rate of 1.0 mL x min(-1). The mobile phase was a mixture of acetonitrile and ion-pair buffer (0.01 mol x L(-1) hexadecyl trimethyl ammonium bromide and 0.01 mol x L(-1) potassium dihydrogen phosphate, adjusted the pH value to 6.8 with potassium hydroxide solution). The resolution values of four isomers were 2.5, 1.20, 1.33, and 1.8. Linear regression analysis for four compounds was performed by the external standard method. Four constituents were linear in the concentration range of 0.005 to 10 microg. The values of relative standard deviation (RSD) of intra-day were 0.12%, 0.66%, 0.99%, and 1.21%, respectively. The limits of detection for four compounds were 15 ng, 20 ng, 12 ng, and 25 ng, respectively. This method was simple, accurate and reproducible. The developed method can be successfully applied to analyze isomers in Photocyanine.
Antineoplastic Agents ; analysis ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Indoles ; analysis ; chemistry ; Isomerism ; Molecular Structure ; Organometallic Compounds ; analysis ; chemistry ; Photochemotherapy ; Photosensitizing Agents ; analysis ; chemistry ; Quality Control

The role of imaging is crucial for the surveillance, diagnosis, staging and treatment monitoring of hepatocellular carcinoma (HCC). Over the past few years, considerable technical advances were made in imaging of HCCs. New imaging technology, however, has introduced new challenges in our clinical practice. In this article, the current status of clinical imaging techniques for HCC is addressed. The diagnostic performance of imaging techniques in the context of recent clinical guidelines is also presented.
Carcinoma, Hepatocellular/*diagnosis/radiography/ultrasonography ; Contrast Media/chemistry ; Ferric Compounds/chemistry ; Humans ; Iron/chemistry ; Liver Neoplasms/*diagnosis/radiography/ultrasonography ; Magnetic Resonance Imaging ; Meglumine/analogs & derivatives/chemistry ; Organometallic Compounds/chemistry ; Oxides/chemistry ; Tomography, X-Ray Computed

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

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

AIMUnderstanding the modes and activities of metal bacterial chlorophylls as PHD sensitizers with DNA.

METHODSThe modes and activities of the interaction of DNA and metal complexes of bacterial chlorophyll, which have been prepared by extraction and synthesis reaction, have been discussed according to the ultraviolet-visual spectrum and nucleic acid electrophoresis.

RESULTSIt indicates that the system of DNA and metal complexes have enchanced the interaction by the ultraviolet-visual spectrum. At the same time, it also indicates that metal complexes of bacterial chlorophyll and DNA have different combining way and have strong cutting effect in illumination by the nucleic acid electrophoresis.

CONCLUSIONThis paper proved that metal bacterial chlorophylls as PHD sensitizers have great advantage.

Bacteriochlorophylls ; chemical synthesis ; chemistry ; pharmacology ; Copper ; chemistry ; DNA ; metabolism ; Electrophoresis ; HL-60 Cells ; Humans ; K562 Cells ; Nickel ; chemistry ; Organometallic Compounds ; chemical synthesis ; chemistry ; pharmacology ; Protein Binding ; Spectrophotometry, Ultraviolet ; Zinc ; chemistry

The coordination chemistry theory of traditional Chinese medicine (TCM) plays a very important role on the research of traditional Chinese medicine. The significances of this theory applied in toxicology, pharmacology and the improvement, separation, preparation and analysis of active components in traditional Chinese medicine were summarized in this paper. The conclusions were drawn that the research on thermodynamics and dynamics of TCM coordination chemistry, the relation between existing status of microelements in TCM and toxicity or activity of TCM and the exploitation on adsorbents or chromatographic columns of high performance and high sensitivity analysis methods using the coordination effect may be the key steps in the course of modernization of TCM.
Animals ; Chemistry Techniques, Analytical ; methods ; Chromatography ; methods ; Crystallography, X-Ray ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; toxicity ; Electrochemistry ; methods ; Medicine, Chinese Traditional ; Organometallic Compounds ; chemistry ; Plants, Medicinal ; chemistry ; Trace Elements ; chemistry

OBJECTIVE: To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. MATERIALS AND METHODS: This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (K(trans)) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. RESULTS: P792 group showed a more prominent decrease in K(trans) and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.
Animals ; Antineoplastic Agents/therapeutic use ; Benzophenones/therapeutic use ; Disease Models, Animal ; Heterocyclic Compounds/administration & dosage/*chemistry ; Liver Neoplasms/drug therapy/pathology/*radiography ; *Magnetic Resonance Imaging ; Male ; Organometallic Compounds/administration & dosage/*chemistry ; Rabbits ; Reproducibility of Results ; Valine/analogs & derivatives/therapeutic use

Carbon monoxide has been proved to be an important signal molecule in body. Transition metal carbonyl compounds are solidified form of carbon monoxide. Numerous studies have shown that Ruthenium carbonyl carbon monoxide releasing molecules have a strong pharmacological activity. In this paper, five Ruthenium (II) carbonyl CORMs 1-5 were synthesized and their toxicology, tissue distribution and interaction with blood endogenous substances were investigated. The results showed CORMs' IC50 to fibroblasts are ranged from 212.9 to 2089.2 micromol x L(-1). Their oral LD50 to mouse is between 800 to 1600 mg x kg(-1). After repeated administration, CORMs 1 and CORMs 5 haven't shown an obvious influence to rats' liver and kidney function, but caused the injury to liver and kidney cells. The in vivo distribution result revealed the majority of CORMs were distributed in blood, liver and kidney, only a small part of CORMs distributed in lung, heart and spleen. They could scarcely cross the blood-brain barrier and distribute to brain. The non-CO ligands in structure have an obvious relevance to their in vivo absorption and distribution. Interestingly, CORMs could enhance the fluorescence of bovine serum albumin, and this enhancement was in direct proportion with the concentration of CORMs. Under different conditions, interaction of CORMs with glutathione got different type of products, one is Ruthenium (II) tricarbonyl complexes, and Ruthenium (II) dicarbonyl complexes.
Animals ; Carbon Monoxide ; chemistry ; pharmacokinetics ; toxicity ; Fibroblasts ; drug effects ; Kidney ; drug effects ; Liver ; drug effects ; Mice ; Molecular Structure ; Organometallic Compounds ; chemical synthesis ; chemistry ; pharmacokinetics ; toxicity ; Rats ; Rats, Wistar ; Ruthenium ; chemistry ; pharmacokinetics ; toxicity ; Tissue Distribution