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1.
One hundred eight fertile eggs (Columbia × New Hampshire) were assigned to 10 groups of 10 eggs each (2 control groups had 14 eggs each). Five groups of eggs were inoculated on day 1 of incubation, while the other 5 groups were inoculated on day 10. The inoculum of the 4 treatment groups on both day 1 and 10 consisted of 1,10, or 100 µM purified fumonisin B1 (FB1) or a culture material extract (CME) ofFusarium proliferatum, having known amounts of FB1, FB2 and moniliformin (FB1 20 µM; FB2 4 µM and moniliformin 7 µM). Inoculum consisted of the respective toxin(s) dissolved in 100 µl double distilled, autoclaved water (diluent). Control eggs were inoculated with diluent only. Mortality was both dose- and time-responsive in all treatments. Eggs inoculated on day 1 with 1 µM FB1 had 50% mortality; 10 µM FB1 had 70% mortality; 100 µM FB1 had 100% mortality; and CME had 100% mortality. Eggs inoculated on day 10 with 1,10 or 100 µM FB1 or CME had 30, 60, 90 and 80% mortality, respectively. Normal chicks were hatched from all control eggs. The median death times (MDT50) were inversely dose-responsive in all treatments, ranging from 3.0 to 7.4 days in embryos exposed on day 1 and from 3.2 to 9.0 days in those exposed on day 10. Early embryonic changes in exposed embryos included hydrocephalus, enlarged beaks and elongated necks. Pathologic changes were noted in liver, kidneys, heart, lungs, musculoskeletal system, intestines, testes and brain toxin-exposed embryos.  相似文献   

2.
Xiu  Ruiquin  Xu  Yongxiang  Gao  Shirong 《Hydrobiologia》1989,(1):411-413
The toxicity of deltamethrin, a synthetic pyrethroid insecticide, was determined under standardized conditions (ISO, 1982) in neonates and juveniles of Daphnia magna. Neonates (6 to 24 h old) were more sensitive than juveniles (48 to 72 h old). The 24- and 48-h EC50s (immobilization) in neonates were 0.113 and 0.031 µg l–1, respectively. The toxicity of deltamethrin was highly toxic. The 96-h EC50 was in the ppt (µg l–1) range. Toxicity tests with Daphnia may be used to detect toxic residues in water and sediment in areas treated with deltamethrin and other highly toxic pyrethroid pesticides.  相似文献   

3.
Summary Lung cell culture may be useful as anin vitro alternative to study the susceptibility of the lung to various toxic agents. Lungs from female Wistar rats were enzymatically digested by recirculating perfusion through the pulmonary artery with a sequence of solutions containing deoxyribonuclease, chymopapain, pronase, collagenase, and elastase. Lung tissue was microdissected and resuspended and the cells obtained were washed by centrifugation. By this isolation method, 2×108 cells per rat lung were obtained with an average viability of 97%. Lung cells cultured in medium containing antibiotics and serum maintained a viability of >70% for 5 d. Rat primary lung cells were exposed to various toxic agents and their viability was assessed by formazan production capacity after 18 h of incubation. Compared to rat and mouse hepatocyte cultures (EC50=5.8 mM), rat primary lung cells were much more susceptible to hydrogen peroxide (EC50=0.6 mM). All cell types were equally sensitive to the more potent toxicanttert-butylhydroperoxide (EC50=0.1 mM). Paraquat was more toxic to lung cells (EC50=0.03 mM) than to rat (EC50=2.8 mM) and mouse (EC50=0.2 mM) hepatocytes. In contrast, rat lung cells were less sensitive to sodium nitroprusside (EC50=2.6 mM) compared to rat (EC50=0.2 mM) and mouse (EC50=0.03 mM) hepatocytes. Nitrofurantoin and menadione (at EC50=0.04 mM and 0.006 mM, respectively) were more toxic to rat lung and liver cells than to murine hepatocytes (EC50=0.2 mM and 0.04 mM, respectively). Our findings demonstrate the applicability of this rat primary lung cell culture for studying the effects of lung toxicants. Parts of the study had been presented orally at the meeting of the German Society of Toxicology and Pharmacology in Mainz (FRG), March 15–17, 1994.  相似文献   

4.
Fumonisins have been reported to have diverse effects on animals, including immunosuppression in chickens and feeder calves; therefore, the effects of fumonisin B1 (FB1) on immune function in BALB/c mice was investigated. When administered i.p. with sheep red blood cells (SRBC), 5 to 100 µg of FB1 reduced the number of plaque-forming cells (PFC) produced against SRBC; however, when administered daily, 1 to 50 µg of FB1 caused a 4 to 12-fold increase in the number of PFC after SRBC injection. Therefore, FB1 is not only immunosuppressive; but also, immunostimulatory. To test the possibility that there may have been an immune response to FB1 as an antigen, FB1 was injected into mice and the number of splenic cells forming rosettes on FB1-treated SRBC was determined. There were dose-dependent increases in the antigen-binding cells, with up to 4.9- and 4.6-fold increases, respectively, upon primary and secondary immunization. FB1-binding immunoglobulins could be detected in sera from some treated mice, but this response was not obtained in every experiment. In summary, these results show that FB1 has diverse effects on the immune system, causing both stimulation and suppression of the response to foreign antigens, and apparently inducing an antigenic response to FB1.Abbreviations DMEM Dulbecco's Modified Eagle's Medium - FB1 fumonisin B1 - FCS fetal calf serum - PBS phosphate buffered saline - PFC plaque forming cells - RFC rosette forming cells - SRBC sheep red blood cells  相似文献   

5.
The chronic and acute toxicity of fumonisin B1 (FB1), a mycotoxin from Fusarium moniliforme, to the larvae of the yellow mealworm, Tenebrio molitor, was assessed. The toxin was administered via the diet or injected directly into the larvae. Young T. molitor larvae fed on a diet containing 450 µg FB1 per g diet exhibited reduced growth performance but only after consuming the fumonisin-contaminated diet for several weeks. FB1-contaminated diet also reduced the rate of carbon dioxide production, food consumption and protein metabolism. The concentrations of FB1 in the diet did not increase mortality, even when tested at the highest dose of 450 µg FB1 per g of diet. Injection of 25 ng FB1 per larva decreased the CO2 production, but became significant only 11 days after the injection and was reversible with time. A parallel analysis of the retention of FB1 by the larvae indicated that about 40% of the ingested FB1 was excreted in the faeces.  相似文献   

6.
Fumonisins are mycotoxins produced by Fusarium moniliforme, F. proliferatum, and related Fusarium species found on corn. They occur naturally in corn-based feeds and foods and are suspected human esophageal carcinogens. Fumonisin B1 (FB1), the most common homologue, causes the animal diseases associated with F. moniliforme. Hepato- and nephrotoxicities, disrupted sphingolipid metabolism, and liver cancer have been found in rats fed FB1. To determine the in vivo effects of diets containing fumonisins B2 (FB2) or B3 (FB3), male rats were fed culture materials (CM) of FB1 non-producing F. moniliforme isolates to provide low (4.6–6.7 ppm), mid (32–49 ppm) or high (219–295 ppm) dietary levels of either FB2 (FB2CM) or FB3 (FB3CM). Other groups were fed culture material of an FB1 producing isolate (FB1CM) providing 6.9, 53 or 303~ppm total fumonisins (FB1 : FB2 : FB3 = 1.0 : 0.38 : 0.15) and a tenth group was fed a control diet having no detectable fumonisins. One-half (n = 5/group) the animals were killed after three weeks, at which time the toxicological and histopathological effects of the three culture materials were similar, mimicked the effects of FB1, and included decreased body weight gains, serum chemical indicators of hepatotoxicity, decreased kidney weights, and apoptosis of hepatocytes and kidney tubular epithelium. FB1CM, FB2CM, and FB3CM affected sphingolipids, causing increased sphinganine to sphingosine ratios (Sa/So) in both liver and kidneys. The remaining animals (n = 5/group) were fed a control diet for three additional weeks. All body weight and tissue specific effects, including increased Sa/So, induced by the FB2CM, FB3CM and low level FB1CM diets were absent following the recovery period. Except for mild biliary lesions found in the high dose FB1CM group and a few apoptotic hepatocytes present in one mid- and two high-dose FB1CM rats, no evidence of toxicity remained in these groups following the recovery period.This revised version was published online in October 2005 with corrections to the Cover Date.  相似文献   

7.
Fumonisins: Isolation,chemical characterization and biological effects   总被引:2,自引:2,他引:0  
The fumonisin B mycotoxins (FB1 and FB2) have been purified and characterized from corn cultures of Fusarium moniliforme strain MRC 826. Fumonisin B1 (FB1, the major fumonisin produced in culture, has been shown to be responsible for the major toxicological effects of the fungus in rats, horses and pigs. Recent investigations on the purification of compounds with chromatographic characteristics similar to FB1 have led to the identification of two new fumonisins, FB3 and FB4. Fumonisins A1 and A2, the N-acetyl derivatives of FB1 and FB2 respectively, were also purified and shown to be secondary metabolites of the fungus. Short-term carcinogenesis studies in a rat liver bioassay indicated that over a period of 15 to 20 days, at dietary levels of 0.05–0.1%, FB2 and FB3 closely mimic the toxicological and cancer initiating activity of FB1 and thus could contribute to the toxicological effects of the fungus in animals. In contrast, no biological activity could be detected for FA1 under identical experimental conditions. These studies and others have indicated that the fumonisin B mycotoxins, although lacking mutagenicity in the Salmonella test or genotoxicity in the DNA repair assays in primary hepatocytes, appear to induce resistant hepatocytes similar to many known hepatocarcinogens.  相似文献   

8.
The effects of fumonisins B1FB1, B2(FB{2}), and the backbone of fumonisin B1 remaining after hydrolysis of the tricarballylic groups with base (HFB1) on sphingolipid biosynthesis were studied in both primary rat hepatocytes and pig kidney epithelial cells (LLC-PK1). Fumonisins were potent inhibitors of sphingolipid biosynthesis in hepatocytes (IC50 of FB1=0.1 M), but overt toxicity was not observed. In renal cells, fumonisins also inhibited sphingosine biosynthesis (IC50 for FB1=35 M), and caused decreased cell proliferation as well. Higher doses (70 M) killed renal cells after exposure for 3 days. The inhibition of de novo sphingolipid biosynthesis was specific, and appeared to be at the site of ceramide synthase, which catalyzes the formation of dihydroceramide or ceramide by the addition of the amide-linked fatty acid to sphinganine or sphingosine. These results may account for the ability of fumonisins to cause equine leucoencephalomalacia and to promote tumor formation.  相似文献   

9.
We investigated the stereoselective degradation kinetics and toxicity of fluroxypyr methylheptyl ester (FPMH) in rat hepatocytes using a chiral high‐performance liquid chromatographic method. The T1/2 of (−)‐FPMH was about two times longer than that of (+)‐FPMH after the rat hepatocytes were incubated with 10, 20, and 50 μM of rac‐FPMH. There was no chiral conversion or transformation during their incubation with the hepatocytes. Toxicity differences were observed among the two enantiomers of FPMH and fluroxypyr (FP) in their EC50 values in rat hepatocytes. Of all the tested compounds, FP was most toxic to the rat hepatocytes. The (−)‐FPMH enantiomer showed higher toxicity than the (+)‐FPMH, whereas the racemic mixture displayed intermediate toxicity. The data presented here are important for a more thorough understanding of this pesticide and should be useful for its full environmental assessment. Chirality, 2011. © 2011 Wiley‐Liss, Inc.  相似文献   

10.
Pregnant Charles River CD1 mice were treated with a semipurified extract ofFusarium moniliforme culture containing 0, 12.5, 25, 50 or 100 mg FB1/kg each day orally (diluted in distilled water) between gestational days (GD) 7 and 15 to evaluate the developmental toxicity of FB1. Following sacrifice of dams on GD 18, litters were examined for gross abnormalities and divided equally for skeletal or visceral examination by routine techniques. Significant maternal mortality was observed at doses of 50 and 100 mg FB1/kg. Dose-dependant decreases in maternal body weight gains, number of live offsprings per litter, and mean body weight of the offspring were produced at FB1 doses of 25 mg/kg or higher. The percentage of implants resorbed increased at all doses in a dose-dependant manner. A dose-dependant increase, except at the lowest dose tested, in the incidence of ossification deficits involving digits and sternum, short and wavy ribs, and hydrocephalus of lateral and third ventricles was also evident. Cleft palate was seen only at the highest FB1 dose. Maternal intoxication manifested as a dose-dependant increase in the severity of ascites associated mainly with increased histopathologic scores reflecting hepatocellular damage at day 18. Concommittant increases in serum alanine amino transferase (ALT) on GD 12, reflecting parenchymal liver cell damage, was also observed at all doses above 12.5 mg of FB1/kg. These results suggest that FB1-containingF. moniliforme culture extract is developmentally toxic in mice, and that this toxicity may be mediated by maternal hepatotoxicity.  相似文献   

11.
The genotoxic potential of fumonisin B1 (FB1) in vivo in BALB/c mice (male and female) was assessed by induction of micronuclei (MN) formation in bone marrow polychromatic erythrocytes. The ratio of polychromatic erythrocytes to normochromatic erythrocytes (PCE/NCE) was also determined. Mice were injected intraperitoneally (i.p.) with FB1 at a low dose (0.1 mg?kg?1 body mass), middle dose (1.0 mg?kg?1 body mass) and high dose (10 mg?kg?1 body mass) as single and multiple doses in normal saline to test the genotoxicity. Mitomycin C, a known clastogen, was used as positive control. The frequency of MN and the PCE/NCE value in animals treated with FB1 at low, middle, and high doses in single dose studies, and the frequency of MN in multiple dose studies, were statistically non-significant from that of the controls injected with saline only. The multiple dose studies at all doses revealed that the PCE/NCE value was found to be reduced upon exposure to FB1 as compared to the controls. In animals injected with multiple low doses of FB1, the PCE/NCE value was found to be 0.66 in males and 0.82 in the females; at multiple middle doses the value was 0.30 in males and 0.41 in the females and was statistically significant (p?<?0.001); however, at multiple high doses, the ratio was found to be 0.36 in both males and females. The present study confirms that FB1 is non-genotoxic in nature while the reduced ratio of PCE/NCE suggests the cytotoxic nature of FB1.  相似文献   

12.
DNA Damage in Astrocytes Exposed to Fumonisin B1   总被引:2,自引:0,他引:2  
Fumonisins are a group of toxic metabolites mainly produced by Fusarium moniliforme and Fusarium proliferatum, fungi that commonly occur on corn throughout the world. Fumonisin B1 (FB1), structurally resembling sphingoid bases, is an inhibitor of ceramide synthase, a key enzyme involved in de novo sphingolipid biosynthesis and in the reacylation of free sphingoid bases derived from sphingolipid turnover. This inhibitory effect leads to accumulation of free sphinganine (SA) and sphingosine (SO), inducing cell death. However, little is known on the down stream effectors activated by these sphingolipids in the cell death signaling pathway. We exposed rat astrocytes to FB1 with the aim of evaluating the involvement of oxygen free radicals and of some other biochemical pathways such as caspase-3 activity and DNA damage. Our results indicate that FB1 treatment (48, 72 h and 6 days in vitro, DIV, and 10, 50, 100 M) does not affect cell viability. Conversely, after 72 h of treatment, FB1 (50 and 100 M) induced DNA damage and an enhancement of caspase-3 activity compared to controls. In addition, FB1 increased the expression of HSP70 at 10 and 50 M at 48, 72 h, and 6 DIV of treatment. We conclude that DNA damage of apoptotic type in rat astrocytes is caused by FB1 and that the genotoxic potential of FB1 has probably been underestimated and should be reconsidered.  相似文献   

13.
The anti-arrhythmic effects of long-chain polyunsaturated fatty acids (PUFAs) may be related to their ability to alter calcium handling in cardiac myocytes. We investigated the effect of eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) on calcium sparks in rat cardiac myocytes and the effects of these PUFAs and the monounsaturated oleic acid on cardiac calcium release channels (RyRs). Visualization of subcellular calcium concentrations in single rat ventricular myocytes showed that intensity of calcium sparks was reduced in the presence of EPA and DHA (15 µM). It was also found that calcium sparks decayed more quickly in the presence of EPA but not DHA. Sarcoplasmic vesicles containing RyRs were prepared from sheep hearts and RyR activity was determined by either [3H]ryanodine binding or by single-channel recording. Bilayers were formed from phosphatidylethanolamine and phosphatidylcholine dissolved in either n-decane or n-tetradecane. EPA inhibited [3H]ryanodine binding to RyRs in SR vesicles with K I = 40 µM. Poly- and mono-unsaturated free fatty acids inhibited RyR activity in lipid bilayers. EPA (cytosolic or luminal) inhibited RyRs with K I =32 µM and Hill coefficient, n 1 = 3.8. Inhibition was independent of the n-alkane solvent and whether RyRs were activated by ATP or Ca2+. DHA and oleic acid also inhibited RyRs, suggesting that free fatty acids generally inhibit RyRs at micromolar concentrations.  相似文献   

14.
Fumonisin B1 (FB1) causes equine leukoencephalomalacia, porcine pulmonary edema, and liver tumors and chronic nephritis in rats. To investigate mechanisms by which FB1 induces toxicity, effects of FB1 on cellular glutathione (GSH) redox status and GSH depletion on FB1 toxicity in pig kidney (LLC-PK1) cells were studied. Treatment of LLC-PK1 cells with 50 μM FB1 for 24 hours significantly decreased cellular GSH contents from 56 ± 3.2 to 42.7 ± 4.4 nmol/mg protein (p < 0.05) and increased the activities of glutathione reductase (GR) from 25.7 ± 2.4 to 35.7 ± 5.0 μmol NADPH/mg protein (p < 0.05). The activities of glutathione peroxidase (GSHpx), catalase, and Cu,Zn-superoxide dismutase (SOD) were not changed by this treatment. Treatment of LLC-PK1 cells for 12 hours with 0.1. mM buthionine sulfoximine (BSO), a selective inhibitor of the enzyme γ-glutamylcysteine synthetase that catalyzes the rate-limiting reaction in de novo GSH synthesis, decreased cellular GSH levels to about 20% of that found in the control cells. The cells pretreated with 0.1 mM BSO for 12 hours were significantly sensitized to the FB1 cytotoxicity as determined by a long-term survival assay (p < 0.05). The results demonstrate that FB1 changes GSH redox cycle status in LLC-PK1 cells, and GSH may play a role in cytoprotection against FB1 toxicity. © 1997 John Wiley & Sons, Inc.  相似文献   

15.
Adequate copper (Cu2+) concentrations are required for plants; however, at higher concentrations it can also cause multiple toxic effects. In the present study, lipid peroxidation, hydrogen peroxide levels as well as ascorbate peroxidase (APX: EC 1/11/1/11) and catalase (CAT: EC 1.11.1.6) activities were determined in Lycopersicum esculentum Mill. and Cucumis sativus L. seedlings after 7-day exposure to copper sulfate. In addition, DNA damage in these two crops was assessed by measuring micronucleus (MN) frequency and tail moments (TM) as determined by Comet assay. Inhibitory copper concentrations (EC50: 30 and 5.5 ppm for L. esculentum and C. sativus, respectively) were determined according to dose-dependent root inhibition curves, and EC50 and 2×EC50 were applied. Malondialdehyde (MDA) and H2O2 levels significantly increased in all groups studied. CAT activity increased in treatment groups of C. sativus. APX activity increased in L. esculentum seedlings due to 2×EC50 treatment. Reductions in mitotic indices (MI) represented Cu2+dependent root growth inhibition in all treatment groups studied. According to TMs and MN frequencies, copper exposure induced significant DNA damage (p < 0.05) in all study groups, whereas the DNA damage induced was dose dependent in C. sativus roots. In conclusion, Cu2+induced oxidative damage, elevations in H2O2 levels and alterations in APX and CAT activities, as well as significant DNA damage in nuclei of both study groups. To our knowledge, this is the first comparative and comprehensive study demonstrating the effects of copper on two different plant species at relevant cytotoxic concentrations at both biochemical and genotoxicity levels with multiple end points.  相似文献   

16.
Exposure of cardiac myocytes to hyposmotic solution stimulates slowly-activating delayed-rectifying K+ current (IKs) via unknown mechanisms. In the present study, IKs was measured in guinea-pig ventricular myocytes that were pretreated with modulators of cell signaling processes, and then exposed to hyposmotic solution. Pretreatment with compounds that (i) inhibit serine/threonine kinase activity (10-100 μM H89; 200 μM H8; 50 μM H7; 1 μM bisindolylmaleimide I; 10 μM LY294002; 50 μM PD98059), (ii) stimulate serine/threonine kinase activity (1-5 μM forskolin; 0.1 μM phorbol-12-myristate-13-acetate; 10 μM acetylcholine; 0.1 μM angiotensin II; 20 μM ATP), (iii) suppress G-protein activation (10 mM GDPβS), or (iv) disrupt the cytoskeleton (10 μM cytochalasin D), had little effect on the stimulation of IKs by hyposmotic solution. In marked contrast, pretreatment with tyrosine kinase inhibitor tyrphostin A25 (20 μM) strongly attenuated both the hyposmotic stimulation of IKs in myocytes and the hyposmotic stimulation of current in BHK cells co-expressing Ks channel subunits KCNQ1 and KCNE1. Since attenuation of hyposmotic stimulation was not observed in myocytes and cells pretreated with inactive tyrphostin A1, we conclude that TK has an important role in the response of cardiac Ks channels to hyposmotic solution.  相似文献   

17.
Neutral red (NR) in medium was absorbed and concentrated in lysosomes of cultured rat and human hepatocytes. NR uptake increased with the time of incubation and reached a plateau in 2 hr. Uptake was proportional to the concentration of the NR solution and the numbers of viable liver cells. Prolonged culture of hepatocytes increased the numbers of lysosomes, and thus, the dye accumulation. The NR can be extracted from lysosomes for quantitative measurement of hepatocyte viability and cytotoxicity of xenobiotics. With this assay, several serum-free media (e.g., Waymouth's, MEM, LHC-8, etc.) were compared for the maintenance of viable hepatocytes in vitro. Interestingly, LHC-8 medium, which is used to grow human bronchial epithelial cells, best preserved viable rat hepatocytes. The cytotoxic effects of dimethylnitrosamine (DMN) and aflatoxin B1 (AFB1) were examined by NR assay on rat and human hepatocyte cultures and were found to be dependent on dose and time of the exposures. NR50 was 20 mM for DMN and 0.072 µM for AFB1 in rat hepatocytes with 24 hr of exposures and reduced to 12.5 mM for DMN and 0.053 µ uM for AFB1 with 48 fr exposures. Human hepatocytes were more resistant to the toxicity of both chemicals; NR50 values were 100 mM DMN and 1.8 µM AFB1 respectively, for 24 hr treatments. Compared with lactate dehydrogenase (LDH) leakage test, the NR assay was simpler and more sensitive in determining the viability and cytotoxicity of xenobiotics in primary cultures of hepatocytes.Abbreviations NR Neutral Red - MEM Eagle's Minimum Essential Medium - DMN dimethylnitrosamine - AFB1 aflatoxin B1 - LDH lactate dehydrogenase - HBSS Hanks balanced salt solution; - EDTA ethylene bis (oxyethylenenitrilo)-tetraacetic acid - L-15 Leibovitz's 15 - NADH B-nicotinamide adenine dinu - FBS fetal bovine serum - IA immediate autopsy Contribution No. 2816 from Laboratory of Genotoxicology.  相似文献   

18.
Iron-overload disorders cause hepatocyte injury and inflammation by oxidative stress, possibly leading to liver fibrosis and hepatocellular carcinoma. This study investigated the efficacy of sauchinone, a bioactive lignan, in preventing iron-induced liver injury and explored the mechanism of sauchinone's activity. To create iron overload, mice were injected with phenylhydrazine, and the effects on hepatic iron and histopathology were assessed. Phenylhydrazine treatment promoted liver iron accumulation and ferritin expression, causing hepatocyte death and increased plasma arachidonic acid (AA). Sauchinone attenuated liver injury (EC50 = 10 mg/kg) and activated AMPK in mice. Treatment of hepatocytes with iron and AA simulated iron overload conditions: iron + AA synergistically amplified cytotoxicity, increasing H2O2 and the mitochondrial permeability transition. Sauchinone protected hepatocytes from iron + AA-induced cytotoxicity, preventing the induction of mitochondrial dysfunction and apoptosis (EC50 = 1 μM), similar to the result using metformin. Sauchinone treatment activated LKB1, which led to AMPK activation: these events contributed to cell survival. Evidence of cytoprotection by LKB1 and AMPK activation was revealed in the reversal of sauchinone's restoration of the mitochondrial membrane potential by either dominant negative mutant AMPKα or chemical inhibitor. In conclusion, sauchinone protects the liver from toxicity induced by iron accumulation, and sauchinone's effects may be mediated by LKB1-dependent AMPK activation.  相似文献   

19.
We synthesized new tropolone derivatives substituted with cyclic amines: piperidine, piperazine or pyrrolidine. The most active anti-helicase compound (IC50 = 3.4 μM), 3,5,7-tri[(4′-methylpiperazin-1′-yl)methyl]tropolone (2), inhibited RNA replication by 50% at 46.9 μM (EC50) and exhibited the lowest cytotoxicity (CC50) >1 mM resulting in a selectivity index (SI = CC50/EC50) >21. The most efficient replication inhibitor, 3,5,7-tri[(4′-methylpiperidin-1′-yl)methyl]tropolone (6), inhibited RNA replication with an EC50 of 32.0 μM and a SI value of 17.4, whereas 3,5,7-tri[(3′-methylpiperidin-1′-yl)methyl]tropolone (7) exhibited a slightly lower activity with an EC50 of 35.6 μM and a SI of 9.8.  相似文献   

20.
Two new cytosporone derivatives (1 and 2) were isolated from the endophytic fungus Phomopsis sp. PSU-H188 together with 19 known compounds. Their structures were elucidated by analysis of spectroscopic data. Known mycoepoxydiene showed potent cytotoxic activity towards both MCF-7 and noncancerous Vero cell lines with the respective IC50 values of 9.27 and 4.06 μM. It exhibited inhibition on glucose output in mouse primary hepatocytes with the IC50 value of 16.06 μM, but did not show cytotoxicity on primary mouse hepatocytes. Additionally, known cytosporone B displayed protective activity against INS-1 832/13 pancreatic β-cells by an EC50 value of 11.08 μM whereas known diaporthalasin displayed antibacterial activity against methicillin-resistant Staphylococcus aureus with an MIC value of 4 μg/mL. Both of them were noncytotoxic to Vero cells.  相似文献   

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