共查询到20条相似文献,搜索用时 15 毫秒
1.
J E Paulsen K L Reichelt 《Virchows Archiv. B, Cell pathology including molecular pathology》1992,62(3):173-177
A test system for growth regulators based on the time course of liver regeneration in male NMRI mice injected intraperitoneally (ip) with 50 nmol CCl4 at 12 is described. Regenerative DNA synthesis (labelling index) peaked at 36 h after CCl4 injury, and the Colcemid-assessed mitotic rate (MR) at 42 h, i.e., 6 h later. This response pattern was used to assess the effects of factors in liver extracts that regulate or modulate hepatocyte proliferation. The effect of one, two, four or eight ip injections of an aqueous mouse liver extract on MR was tested at 48 h. A 30-70% inhibition was seen only after single injections at 12 h, 29 h or 44 h after CCl4 treatment. A 30-80% stimulation was observed after a single injection of the liver extract at 0, 5 or 24 h, and after two or four injections. The assay system could thus detect the presence of growth modulators in the extract. The experiments also showed that the timing was crucial. We recently isolated and characterized a growth inhibitory pentapeptide from mouse liver extracts. Using a synthetic pentapeptide with the same structure we reassessed the timing for growth inhibition seen with the liver extract. The following test system for growth inhibitors seemed most expedient: inhibitor administration at 29 h to affect G1-S transition, measured as reduced DNA synthesis at 36 h, or inhibitor administration at 44 h to affect G2-M transition, measured as reduced MR at 48 h. 相似文献
2.
Jan-Ying Yeh Bor-Rung Ou Yu-Chuan Liang Joel Burchfiel Judy A. Butler Neil E. Forsberg Philip D. Whanger 《Biometals》2006,19(6):611-621
The objective of this study was to investigate the differential effects of various selenium (Se) compounds and Se-enriched broccoli extracts on cell proliferation and the possible mechanism responsible for the Se-induced growth inhibition. C6 rat glial cells were incubated with graded concentrations up to 1000 nM of selenite, selenate, selenomethionine (SeM), Se-methyl-selenocysteine (SeMCys), high-Se broccoli (H-SeB) extract or low-Se broccoli (L-SeB) extract for 24 and 48 h. MTT results indicated that all Se sources and levels examined inhibited C6 cell proliferation at 48 h. The results from cell cycle progression and apoptosis analysis indicated that SeM, SeMCys, H-SeB or L-SeB treatments at the concentration of 1000 nM reduced the cell population in G0/G1 phase, but induced G2/M phase arrest and increased apoptosis and secondary necrosis in C6 cells at 24 h. The populations of apoptotic cells and secondary necrotic cells were increased by all Se sources examined. The COMET assay indicated that there was no significant DNA single-strand break found for all Se treatments in C6 cells for 48 h. In addition, the Se-induced proliferation inhibition may involve a hydrogen peroxide (H2O2)-dependent mechanism with elevated cellular glutathione peroxidase (cGPX) activity. Both H-SeB and L-SeB inhibited C6 cell proliferation but H-SeB was less inhibitory than L-SeB. The proliferation inhibition by H-SeB in C6 cells is apparently related to the increased H2O2 with the elevated cGPX activity, but the inhibition by L-SeB was H2O2-independent without change in cGPX activity. 相似文献
3.
Kjell Elgjo Karl L. Reichelt 《Virchows Archiv. B, Cell pathology including molecular pathology》1990,59(1):89-93
Earlier work has shown that epidermal cells contain a peptide, pyroGlu-Glu-Asp-Ser-GlyOH, that induces a moderate but long-lasting
inhibition of epidermal cell proliferation when given at low (picomol) doses ip in vivo and in vitro. In the present study,
the epidermal pentapeptide was applied topically to the back skin of hairless mice at different concentrations and in a water-miscible
cream. A single topical application of either high (0.25% wt/wt) or low (0.004% or 0.02% wt/ wt) doses of the pentapeptide
was followed by oscillations in epidermal DNA synthesis and G2-M cell flux (mitotic rate). In general, epidermal cell proliferation was inhibited during the first 10-day period after treatment
with the two lower doses, while the highest concentration of pentapeptide (0.25%) stimulated epidermal cell proliferation.
In spite of the effects on epidermal cell proliferation the size of the epidermal cell population in the treated area (number
of nucleated cells and epidermal thickness) showed no corresponding alterations. The results could imply that the epidermal
pentapeptide modifies epidermal cell proliferation and terminal differentiation in such a way that the two are balance with
each other. 相似文献
4.
O. H. Iversen O. P. F. Clausen K. Elgjo Ulla M. Iversen R. Rohrbach 《Cell proliferation》1977,10(1):71-79
Hairless male mice were given 2 mg Bleomycin i.p. on two successive days. At different time intervals from 1 to 10 days after the last Bleomycin injection, groups of animals were killed and water extracts of homogenized skin were made. These extracts, supposed to contain the epidermal G1 and G2 chalones, were injected into female hairless mice, and their growth inhibitory potency determined by two methods. 5 mg of lyophilized crude skin extract were injected i.p. together with Colcemid, and the animals killed 4 hr later. The number of Colcemid-arrested mitoses was determined, and was considered to be a measure of the G2 inhibitor present in the skin extracts. 10 mg of the same extracts were injected i.p., and these animals also got 3H-TdR i.p. 12 hr later, and were killed after a subsequent 30 min. The epidermal LI was determined, and was considered to be a measure of the epidermal G1 factor in the skin extracts. The results obtained were compared to the effect of Bleomycin alone and to the effects of skin extracts from non-Bleomycin-treated animals. The results show that Bleomycin provoked slight alterations in the growth-inhibitory potency of the G1 chalone, whereas significant effects were seen in the G2 chalone. There was an increased amount of growth-inhibiting factors on days 2 and 3, and on days 8–10. The results are discussed and it is concluded that the most probable hypothesis is that Bleomycin, in addition to its known inhibitory effect on epidermal cell proliferation, exerts growth inhibition by accumulation of cells with high growth inhibitory potency. An initial, additional direct effect of Bleomycin on the chalone system cannot be excluded. 相似文献
5.
Nan-Chieh Huang Ru-Lai Huang Xiao-Fan Huang Kai-Fu Chang Chien-Ju Lee Chih-Yen Hsiao Shan-Chih Lee Nu-Man Tsai 《Bioscience reports》2021,41(7)
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for the fourth leading cause of all cancer deaths. Scientific evidence has found that plant extracts seem to be a reliable choice due to their multitarget effects against HCC. Juniperus communis has been used for centuries in traditional medicine and its anticancer properties have been reported. As a result, the purpose of the study was to investigate the anticancer effect and mechanism of J. communis extract (JCo extract) on HCC in vitro and in vivo. In the present study, we found that JCo extract inhibited the growth of human HCC cells by inducing cell cycle arrest at the G0/G1 phase, extensive apoptosis and suppressing metastatic protein expressions in HCC cells. Moreover, the combinational treatment of JCo and VP-16 was found to enhance the anticancer effect, revealing that JCo extract might have the potential to be utilized as an adjuvant to promote HCC treatment. Furthermore, in vivo study, JCo extract significantly suppressed HCC tumor growth and extended the lifespan with no or low systemic and pathological toxicity. JCo extract significantly up-regulated the expression of pro-apoptotic proteins and tumor suppressor p53, suppressed VEGF/VEGFR autocrine signaling, down-regulated cell cycle regulatory proteins and MMP2/MMP9 proteins. Overall, our results provide a basis for exploiting JCo extract as a potential anticancer agent against HCC. 相似文献
6.
Y. van der Meer H. L. Roepers-Gajadien J. A. G. Davids R. Huiskamp A. L. Bootsma D. G. de Rooij 《Virchows Archiv. B, Cell pathology including molecular pathology》1992,61(1):323-329
The sensitivity of resting and proliferating cells of the seminal vesicle to X-irradiation and adriamycin has been investigated.
Stimulation with testosterone propionate (250 μg/day) was started 11 days after castration in BALB/c mice. X-rays (2.5–7.5
Gy total body irradiation) and intraperitoneal injections of adriamycin (4–16 mg/kg body weight) were administered at various
times before or after induction of proliferation by testosterone injection. The DNA contents and the weights of the seminal
vesicles were determined at 4 days after the start of stimulation. A D0 for X-rays of about 10 Gy was found for the seminal vesicle epithelium. For both X-irradiation and adriamycin no significant
differences in sensitivity were observed between quiescent (G0) and proliferating (G1; S) seminal vesicle cells. 相似文献
7.
SPERMATOGONIAL CHALONE(S): EFFECT ON THE PHASES OF THE CELL CYCLE OF TYPE A SPERMATOGONIA IN THE RAT
Adult rats with X-irradiated testes were used to analyze the effect of the spermatogonial chalone(s) on the phases of the cell cycle of type A spermatogonia. Twelve days after irradiation, the animals were used in two experiments designed to test the existence of hypothetical G2 and S phase chalones. For the G2 assay, rats injected twice with testicular extract (Group I), liver extract (Group II) or physiological saline (Group III) were killed 10 hr after the initial injection. Mitoses of type A, Intermediate and type B spermatogonia were counted in whole mounts of dissected seminiferous tubules. To test for an S phase inhibitor, two groups of rats were given multiple injections of either testicular extract (Group IV) or saline solution (Group V). Twenty-two hr after the first injection they were injected with [3H]thymidine and killed 2 hr later. Silver grains over labelled type A nuclei were counted in radioautographed sections of testes from these animals. The average grain counts were identical in Groups IV and V, indicating that the testicular extract did not affect type A spermatogonia during the S phase. Counts of type A mitoses in Groups I, II and III revealed that in the animals injected with the testicular extract (Group I) the number of divisions was 50% lower than in the control groups (Groups II and III). In contrast, mitotic activity of differentiating spermatogonia (In + B) was similar in all three groups of animals. This result is attributed to a testicular chalone which specifically inhibits type A spermatogonia during the G2 phase of the cell cycle. Indirect evidence for a G1 spermatogonial chalone is also presented, as a result of an analysis of published data (Clermont & Mauger, 1974). 相似文献
8.
The incorporation of [35S]-SO4 into glycosaminoglycans of liverin vivo and in in liver slices and into the glycosaminoglycans associated with the hepatic plasma membrane of rats at different periods
after a heavy dose of CC14 have been studied. The incorporation of [35S]-SO4 into total glycosaminoglycans decreased to as low as 40% of the control
at 24 h after the administration of CC14 and later on increased reaching a maximum on the 4th day. The amount of [35S]-SO4
incorporation into heparan sulphate was also reduced to about 40% of control at 12–24 h after the onset of injury and increased
thereafter reaching a maximum on the 4th day. There was only a partial reduction in the synthesis of chondroitin sulphate
in the early stage of injury and then it steadily increased reaching about 3 times the control level on 4–6 days. The [35S]-SO4-incorporation into dermatan sulphate, after a slight initial decrease remained at the control levels. On the 8th day
after the CCl4-induced liver injury, the rate of [35S]-SO4-incorporation was almost equal to that in normal controls. The incorporation of [35S]-SO4 into hepatic plasma membrane glycosaminoglycans showed a similar change decreasing to about 35% of control at 24h followed
by an increase, reaching normal levels on the 4th day after the administration of CC14. About 90% of the plasma membrane glycosaminoglycans was found to be heparan sulphate. The yield of plasma membrane from
normal and CCl4-induced regenerating liver was found to be similar and therefore the results obtained were not due to difference in the yield
of the membrane preparation. The data also indicate that there was no difference in the degree of sulphation. The significance
of these changes in the metabolism of sulphated glycosaminoglycans particularly plasma membrane heparan sulphate in tissue
regeneration has been discussed. 相似文献
9.
M.M. Jonah E.A. Cerny Y.E. Rahman 《Biochimica et Biophysica Acta (BBA)/General Subjects》1978,541(3):321-333
Multilamellar liposomes were prepared with various asialoglycolipids, gangliosides, sialic acid, or brain phospholipids in the liposome membrane and with ethylenediaminetetraacetic acid (EDTA) encapsulated in the aqueous compartments. The liposomes containing glycolipids or sialic acid were prepared from a mixture of phosphatidylcholine, cholesterol, and one of the following test substances: galactocerebroside, glucocerebroside, galactocerebroside sulfate, mixed gangliosides, monosialoganglioside GM1, monosialoganglioside GM2, monosialoganglioside GM3, disialoganglioside GD1a, or sialic acid. The liposomes containing brain phospholipids were mixtures of either sphingomyelin and cholesterol or a brain total phospholipid extract and cholesterol. Distribution of 14C-labeled EDTA were determined in mouse tissues from 15 min to 6 h or 12 h after a single injection of liposome prepartion. Liver uptake of encapsulated EDTA was lowest from all liposome preparations containing sialic acid or sialogangliosides regardless of the amount of sialic acid moiety present or the identity of the particular ganglioside; highest uptake of encapsulated EDTA by liver was from the liposomes containing galactocerebroside or brain phospholipids. Lungs and brain took up the largest amounts of EDTA from liposomes containing sphingomyelin and lesser amounts from liposomes containing GD1a. Use of mouse brain phospholipid extract to prepare liposomes did not increase uptake of encapsulated EDTA by the brain. EDTA in liposomes containing monosialogangliosides, brain phospholipids, galactocerebroside, or sialic acid was taken up well by spleen and marrow. Highest thymus uptake of encapsulated EDTA was from liposomes containing GD1a. These results demonstrate that inclusion of sialogangliosides in liposome membranes decreases uptake of liposomes by liver, thus making direction of encapsulated drugs to other organs more feasible. Liposomes containing glycolipids also have potential uses as probes of cell surface receptors. 相似文献
10.
《Free radical research》2013,47(1-5):299-308
With cultured hepatocytes it was studied whether CCl4-induced inhibition of secretion of VLDL and HDL from liver cells is a consequence of covalent binding of CC14 metabolites (i.e. CO,; CC1,00) to cell constituents or of membrane damage by lipid peroxidation. Comparing the kinetics of inhibition of lipoprotein secretion with that of CCl4-bioactivation it was found, that covalent binding of (HC)-CC14 occurred at early time points (5 min) after CC14 administration and inhibited the lipoprotein secretion. At 100μM CC14 it was depressed by 53% within 60min. Incubations of CC14-treated cells with increasing concentrations of vitamin E blocked lipid peroxidation, but lipoprotein secretion was still inhibited. Piperonyl butoxid, a radical scavenger, protected against CCl4-induced inhibition of lipoprotein section, lipid peroxidation and covalent binding.These results show that during the early phases of CC14 poisoning fat accumulation is the consequence of covalent binding of CC14 metabolities to cell structures. 相似文献
11.
Isabelle Rauly-Lestienne Fabrice LestienneMarie-Christine Ailhaud Johan BinesseAdrian Newman-Tancredi Didier Cussac 《Cellular signalling》2011,23(1):58-64
Following agonist action, G-protein-coupled receptors may exhibit differential coupling to G-proteins or second messenger pathways, supporting the notion of agonist-directed trafficking. To explore these mechanisms, we have designed and transfected synthetic siRNA duplexes to knockdown different Gα subunits in Chinese hamster ovary (CHO) cells expressing human (h)5-hydroxytryptamine 1A receptors (CHO-h5-HT1A). siRNAs against Gαi2 and Gαi3 transfected alone or in combination caused a large decrease in the corresponding mRNA level (64-80%) and also at the protein level for Gαi3 (60-70%), whereas a non-specific siRNA showed no effect. In membranes of CHO-h5-HT1A, 5-HT stimulated guanosine-5′-O-(3-[35S]thio)-triphosphate ([35S]GTPγS) binding was differentially affected by transfection of siRNAs against Gαi protein, siRNAs against Gαi2 inducing a more important decrease in the efficacy of 5-HT than transfection of siRNAs against Gαi3. The high potency component was abolished after transfection of siRNAs against Gαi3 and the lower potency component was suppressed after transfection of siRNAs against Gαi2. To directly investigate Gαi3 activation we used an antibody-capture/scintillation proximity assay. (+)8-OH-DPAT yielded bell-shaped curves for Gαi3 activation, a response that was abolished after transfection of siRNAs against Gαi3 protein. Interestingly, (+)8-OH-DPAT yielded a sigmoidal response when only Gαi3 protein was expressed. These data suggest that when efficacious agonists attain a high level of occupation of h5-HT1A receptors, a change occurs that induces coupling to Gαi2 protein and suppresses signalling through Gαi3 subunits. 相似文献
12.
Yuh-Fung Chen Jai-Sing Yang Wen-Shin Chang Shih-Chang Tsai Shu-Fen Peng Yuan-Ru Zhou 《Journal of biomedical science》2013,20(1):18
Background
Houttuynia cordata Thunb (HCT) is commonly used in Taiwan and other Asian countries as an anti-inflammatory, antibacterial and antiviral herbal medicine. In this study, we investigated the anti-human lung cancer activity and growth inhibition mechanisms of HCT in human lung cancer A549 cells.Results
In order to investigate effects of HCT on A549 cells, MTT assay was used to evaluate cell viability. Flow cytometry was employed for cell cycle analysis, DAPI staining, and the Comet assay was used for DNA fragmentation and DNA condensation. Western blot analysis was used to analyze cell cycle and apoptotic related protein levels. HCT induced morphological changes including cell shrinkage and rounding. HCT increased the G0/G1 and Sub-G1 cell (apoptosis) populations and HCT increased DNA fragmentation and DNA condensation as revealed by DAPI staining and the Comet assay. HCT induced activation of caspase-8 and caspase-3. Fas/CD95 protein levels were increased in HCT-treated A549 cells. The G0/G1 phase and apoptotic related protein levels of cyclin D1, cyclin A, CDK 4 and CDK 2 were decreased, and p27, caspase-8 and caspase-3 were increased in A549 cells after HCT treatment.Conclusions
The results demonstrated that HCT-induced G0/G1 phase arrest and Fas/CD95-dependent apoptotic cell death in A549 cells 相似文献13.
Brian J. Day Gary P. Carlson Dennis B. Denicola 《Journal of biochemical and molecular toxicology》1993,8(1):11-18
Induction of P450HE1 by pyridine was compared with that by ethanol, and the resulting potentiation of the pneumotoxicity and hepato-toxicity following carbon tetrachloride inhalation by pyridine was examined. Rats were treated with ethanol as either a 10% solution in the drinking water or as a daily bolus (3 ml/kg, ip) dose for 7 days or one bolus dose of pyridine (200 mg/kg, ip) and compared for P450IIE1 apoprotein content by immunoblot analysis. Ethanol in the drinking water and pyridine elevated both hepatic and pulmonary P450IIE1 apoprotein content, but bolus dose ethanol did not. The induction was greatest in the pyridine group. In the interaction study, rats were treated with pyridine (200 mg/kg, ip) and 12 hours later were exposed to CC14 (8000 ppm for 3 hours). Pulmonary injury and hepatic damage were assessed 24 hours later by bronchoalveolar lavage fluid (BALF) analysis [γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), and total protein] and serum sorbitol dehydrogenase (SDH) activity, respectively. Pyridine alone had no effect on BALF or SDH but enhanced GGT and LDH release into the BALF and SDH release into the serum when compared with CC14 exposure alone. Evaluation of the liver at the light microscopic level revealed characteristic CCl4-induced centrilobular necrosis which was potentiated by pyridine. No changes were observed in the lung by light microscopic evaluation. Pyridine induced pulmonary and hepatic microsomal apoprotein levels of cytochrome P450IIE1 two- and 2- to sixfold, respectively. Exposure to CC14 decreased hepatic but not pulmonary P450IIE1 levels. Induction of cytochrome P450IIE1 by pyridine increases the bioactivation of CC14 in both the liver and lung, leading to enhanced toxicity. 相似文献
14.
J. E. Keys J. P. Van Zyl H. M. Farrell Jr. 《In vitro cellular & developmental biology. Animal》1994,30(1):50-55
Summary Mammary and adipose explants from eight mid-lactation Holstein cows were co-cultured for 24 h in the presence or absence of
liver explants, 1 μg/ml pituitary bovine somatotrophin, or 100 ng/ml insulinlike growth factor-I. Liver explants in the media
significantly depressed DNA and protein synthesis by mammary tissue as measured by [14C]-thymidine and amino acid incorporation. As measured by flow cytometry, the concentration of DNA in the G0G1 and G2M cells and the percentage of cells in the G0G1 population of mammary tissue was also significantly depressed by liver tissue. Changes in the percentage of cells in the
S and G2M phases were not significant. Insulinlike growth factor-I in the presence of liver explants depressed protein synthesis,
thymidine incorporation, and the concentration of DNA in the G0G1 and G2M cells compared to control but did not affect the percentage of cells in the G0G1, S, or G2M phases. Previously it was assumed that changes in [14C]thymidine incorporation indicated that changes in cell division were occurring. Flow cytometry revealed that changes in
DNA content of mammary cells as a result of liver or hormonal stimulation were not due to changes in cell division. Indications
are that differences in cellular DNA content result from changes in the rate of amplification of individual genes responsible
for milk protein synthesis. 相似文献
15.
Mark J. Vocci John W. Combs Elizabeth A. Hillman James H. Resau Benjamin F. Trump 《In vitro cellular & developmental biology. Plant》1983,19(12):881-891
Summary The adaptation of normal human esophageal explants to organ culture for the first 33 d of in vitro growth was evaluated using
histomorphology and [3H]TdR autoradiography combined with mitotic blockade. On the 3rd d in culture, extensive desquamation of superficial cells
reduced the epithelium to about four cell layers. Thereafter, the epithelium remained atrophic, with a relative increase in
basal and suprabasal cells. The percentage of cells synthesizing DNA was greatest from Day 4 through 8, just after desquamation,
and reached a maximum on Day 4 (24 h [3H]TdR labeling index of 62%). The labeling index (LI) fluctuated, thereafter, but remained high (26% on Day 33). During the
last 6 h of each [3H]TdR labeling interval, mitosis was blocked by colcemid. The 6 h mitotic rate (MR) was a reasonably constant fraction of
the LI (maximum at 4 d: MR=1.44%), but was much lower than predicted by [3H]TdR labeling indicating the loss of large numbers of cells after DNA synthesis but before or during mitosis. Unlabeled mitotic
figures appeared between Days 1 to 3 and 6 to 33, suggesting that the epithelium initially contained a considerable population
of cells arrested or delayed in G2 and continued to generate cells that remained in premitosis longer than 24 h.
These results indicate that the atrophy observed in vitro is characterized by a relative increase in the basal and suprabasal
cell category, a high replication rate, initial recruitment of cells arrested in premitosis, and rapid cell turnover with
significant loss of cells at the premitotic or mitotic step, or both. Thus it seems that human esophageal epithelium grown
in organ culture is a satisfactory substrate for experimentation (for example, in vitro carcinogenesis) that requires cell
replication. However, there are major differences between the kinetics of esophageal epithelium in vivo and in vitro.
Supported in part by Contract NOI-CP-75909 and NOI-CP-25604-59 from the National Cancer Institute, Bethesda, MD. 相似文献
16.
A. Asadi Sardari A.A. Hojat Jalali D. Safaee 《Archives Of Phytopathology And Plant Protection》2013,46(4):365-375
Root-knot nematode, Meloidogyne javanica, is a major problem confronting greenhouse’s productions, field crops, vegetables, grapevines and almond rootstocks in Kermanshah province, Iran. Nematicides are not affordable to control this nematode. In the search for alternatives to chemicals control of nematodes, this research has dealt with nematicidal effects of crude herbal extracts on the root-knot nematodes. This study aimed to evaluate the effect of 21 endemic and exotic herbal extracts belong to 12 families of flowering plants in comparison with chicken manure and chemical nematicide (Temik) to control root-knot nematodes in in vitro conditions. The nematodes were pured and mass multiplied on tomato in the soil at greenhouse conditions. In order to study the effect of herbal extracts on mortality of second-stage juveniles (J2), a 6?mL of each extract was poured in sterilised Petri dish and 54?±?4 juveniles were added. Distilled water was used as control and treatments replicated four times and incubated at ambient temperature. The LC50 value of each extract was determined by assessing the mortality of juveniles (in the range of 5–95%) after 24, 48 and 72 h. Comparison between LC50 value of the extracts indicated that Cinnamomum zeylanicum and Eugenia caryophillata are the most effective crude extracts on the mortality of juveniles and they were 15.4 and 17.9?mg?mL?1, respectively. Meanwhile, the extract of tobacco, ferulago, garlic, eucalyptus, persan lilac, rattle, oliveria, licorice, russian knapweed, turnsole, sicilian sumac and chicken manure did not have any antinematode activity against fresh second-stage juveniles of the root-knot nematode. 相似文献
17.
Kyu-Bong Kim Myeon Woo Chung So Young Um Ji Seon Oh Seon Hwa Kim Mi Ae Na Hye Young Oh Wan-Seob Cho Ki Hwan Choi 《Metabolomics : Official journal of the Metabolomic Society》2008,4(4):377-392
The primary objective of this study was to discover biomarkers which are correlated with hepatotoxicity induced by chemicals
using 1H NMR spectral data of urine. A procedure of nuclear magnetic resonance (NMR) urinalysis using pattern recognition was proposed
for early screening of the hepatotoxicity of CCl4, acetaminophen (AAP), and d-galactosamine (GalN) in rats. The hepatotoxic compounds were expected to induce necrosis in hepatocytes. This was confirmed
through blood biochemistry and histopathology. CCl4 (1 ml/kg, po) or GalN (0.8 g/kg, ip) was single administered to Sprague–Dawley (S–D) rats and urine was collected every 24 h.
Animals were sacrificed 24 h or 48 h post-dosing. AAP (2 g/kg, po) was administered for 2 days and then the animals were sacrificed
24 h after the last treatment. NMR spectroscopy revealed evidently different clustering between control groups and hepatotoxicant
treatment groups in global metabolic profilings as indicated by partial least square (PLS)-discrimination analysis (DA). In
targeted profilings, endogenous metabolites of allantoin, citrate, taurine, 2-oxoglutarate, acetate, lactate, phenylacetyl
glycine, succinate, phenylacetate, 1-methylnicotinamide, hippurate, and benzoate were selected as putative biomarkers for
hepatoxicity by CCl4, AAP, and GalN. Comparison of our rat 1H NMR PLS-DA data with histopathological changes suggests that 1H NMR urinalysis can be used to predict hepatotoxicity induced by CCl4, AAP, and GalN. 相似文献
18.
Asha Tukappa NK Ramesh L Londonkar Hanumantappa B Nayaka Sanjeev Kumar CB 《Biological research》2015,48(1)
Background
To evaluate the hepatoprotective potential and invitro cytotoxicity studies of whole plant methanol extract of Rumex vesicarius L. Methanol extract at a dose of 100 mg/kg bw and 200 mg/kg bw were assessed for its hepatoprotective potential against CCl4-induced hepatotoxicity by monitoring activity levels of SGOT (Serum glutamic oxaloacetic transaminase), SGPT (Serum glutamic pyruvic transaminase), ALP (Alkaline phosphatase), TP (Total protein), TB (Total bilirubin) and SOD (Superoxide dismutase), CAT (Catalase), MDA (Malondialdehyde). The cytotoxicity of the same extract on HepG2 cell lines were also assessed using MTT assay method at the concentration of 62.5, 125, 250, 500 μg/ml.Results
Pretreatment of animals with whole plant methanol extracts of Rumex vesicarius L. significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver. The biochemical parameters in serum also improved in treated groups compared to the control and standard (silymarin) groups. Histopathological investigation further corroborated these biochemical observations. The cytotoxicity results indicated that the plant extract which were inhibitory to the proliferation of HepG2 cell line with IC50 value of 563.33 ± 0.8 μg/ml were not cytotoxic and appears to be safe.Conclusions
Rumex vesicarius L. whole plant methanol extract exhibit hepatoprotective activity. However the cytotoxicity in HepG2 is inexplicable and warrants further study. 相似文献19.
Quantitative estimates of gibberellin A9 in Norway spruce extracts obtained by gas chromatography-mass spectrometry, radioimmunoassay (RIA_ and bioassay were compared after successive purifications of the extracts. The extracts were assayed in several dilutions with and without the addition of standard gibberellin A9, thus showing the effect of extract components on the response of the assays. Radioimmunoassay produced estimates comparable to gas chromatography-mass spectrometry after one purification step by high-performance liquid chromatography. Extracts purified by polyvinylpyrrolidone-column chromatography and solvent partitioning but not high-performance liquid chromatography resulted in inaccurate RIA estimates. The performance of the RIA could be monitored by logit-log transformations of the standard curve and extract dilution curve and by calculating the slope of the standard addition curve. It was, however, not possible to correct for the interference caused by extract components by the standard addition procedure. Quantifications by Tan-ginbozu dwarf-rice bioassay were accurate, but a large and unpredictable variation makes it unsuitable for quantitative determinations.Abbreviations FW
fresh weight
- GA9
gibberellin A9
- GA9–Me
methylated GA9
- GC-MS
gas chromatography-mass spectrometry
- HPLC
high performance liquid chromatography
- MID
multiple-ion detection
- RIA
radioimmunoassay 相似文献
20.
《Archives of biochemistry and biophysics》1985,238(1):43-48
The O-dealkylation of pentoxyresorufin (7-pentoxyphenoxazone) by rat liver microsomes was examined. The reaction appeared highly specific for certain phenobarbital inducible forms of cytochrome P-450 and was increased 95- to 140-fold by animal pretreatment with phenobarbital (75 mg/kg/day, four ip injections) and ~50-fold by Aroclor 1254 (500 mg/kg, one ip injection) while animal pretreatment with 3-methylcholanthrene (50 mg/kg/day, three ip injections) resulted in less than a 2-fold increase over the rate detected in control microsomes. It was observed that this activity, in microsomes for Aroclor-pretreated rats, was dependent on O2 and was inhibited by metyrapone and SKF 525-A, indicative of cytochrome(s) P-450 mediation in the reaction. When antibodies directed against purified cytochrome(s) P-450S were employed to inhibit the pentoxyresorufin O-dealkylation reaction, antibodies to P-450PB-B greatly inhibited the reaction (>90%), while antibodies to P-450PB-C or P-450PB/PCN-E had minimal effects. Assay of hepatic microsomes from rats which were pretreated with varying doses of phenobarbital (0.9–75 mg/kg/day, four ip injections) indicated that while aminopyrine-N-demethylase activity was induced only 2-fold at the maximum dose (75 mg/kg/day), pentoxyresorufin O-dealkylase activity was induced ~140-fold at this dose and ~4-fold by a dose of phenobarbital as low as 0.9 mg/kg. 相似文献