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1.
《Phytochemistry》1987,26(8):2227-2230
Three insecticidal acetylchromenes, including encecalin, and precocene II were topically administered to adults of the migratory grasshopper Melanoplus sanguinipes. Metabolites formed and excreted via the frass were identified by gas chromatography-mass spectrometry (GC-MS) and by direct comparison with reference compounds obtained by partial synthesis or from plant sources. Of the 12 metabolites found, six compounds were new natural products. Their tentative structure elucidation is described based on MS analysis. The biological importance of the elucidated chromene metabolism in M. sanguinipes is discussed for the excretion and detoxification of potentially hazardous compounds. 相似文献
2.
Albert P. Li 《Chemico-biological interactions》2009,179(1):1-176
Drug metabolism can be a key determinant of drug toxicity. A nontoxic parent drug may be biotransformed by drug metabolizing enzymes to toxic metabolites (metabolic activation). Conversely, a toxic drug may be biotransformed to nontoxic metabolites (detoxification). The approaches to evaluate metabolism-based drug toxicity include the identification of toxic metabolites and the evaluation of toxicity in metabolically competent and metabolically compromised systems. A clear understanding of the role of drug metabolism in toxicity can aid the identification of risk factors that may potentiate drug toxicity, and may provide key information for the development of safe drugs. 相似文献
3.
Aedes aegypti mosquitoes do not have a typical functional urea cycle for ammonia disposal such as the one present in most terrestrial vertebrates. However, they can synthesize urea by two different pathways, argininolysis and uricolysis. We investigated how formation of urea by these two pathways is regulated in females of A. aegypti. The expression of arginase (AR) and urate oxidase (UO), either separately or simultaneously (ARUO) was silenced by RNAi. The amounts of several nitrogen compounds were quantified in excreta using mass spectrometry. Injection of mosquitoes with either dsRNA-AR or dsRNA-UO significantly decreased the expressions of AR or UO in the fat body (FB) and Malpighian tubules (MT). Surprisingly, the expression level of AR was increased when UO was silenced and vice versa, suggesting a cross-talk regulation between pathways. In agreement with these data, the amount of urea measured 48 h after blood feeding remained unchanged in those mosquitoes injected with dsRNA-AR or dsRNA-UO. However, allantoin significantly increased in the excreta of dsRNA-AR-injected females. The knockdown of ARUO mainly led to a decrease in urea and allantoin excretion, and an increase in arginine excretion. In addition, dsRNA-AR-injected mosquitoes treated with a specific nitric oxide synthase inhibitor showed an increase of UO expression in FB and MT and a significant increase in the excretion of nitrogen compounds. Interestingly, both a temporary delay in the digestion of a blood meal and a significant reduction in the expression of several genes involved in ammonia metabolism were observed in dsRNA-AR, UO or ARUO-injected females. These results reveal that urea synthesis and excretion in A. aegypti are tightly regulated by a unique cross-talk signaling mechanism. This process allows blood-fed mosquitoes to regulate the synthesis and/or excretion of nitrogen waste products, and avoid toxic effects that could result from a lethal concentration of ammonia in their tissues. 相似文献
4.
Bernard Testa 《化学与生物多样性》2009,6(11):2055-2070
Two related and significant issues may elicit perplexity in medicinal chemists and are discussed here. First, a broad presentation of the pharmacological and toxicological consequences of drug metabolism should justify the significance of drug metabolism and serve as an incentive to further study. When comparing the pharmacological activities of a drug and its metabolite(s), a continuum is found which ranges from soft drugs (no active metabolites) to prodrugs (inactive per se, as illustrated here with clopidogrel and prasugrel). Innumerable intermediate cases document drugs whose activity is shared by one or more metabolites, as exemplified with tamoxifen. The toxicological consequences of metabolism at the molecular, macromolecular, and macroscopic levels are manyfold. A brief overview is offered together with a summary of the reactions of toxification and detoxification of the antiepileptic valproic acid. The second issue discussed in the review is a comparison of the relative significance of cytochromes P450 and other oxidoreductases (EC 1), hydrolases (EC 3), and transferases (EC 2) in drug metabolism, based on a ‘guesstimate’ of the number of drug metabolites that are known to be produced by them. The conclusion is that oxidoreductases are the main enzymes responsible for the formation of toxic or active metabolites, whereas transferases play the major role in producing inactive and nontoxic metabolites. 相似文献
5.
S. L. Monfort S. K. Wasser K. L. Mashburn M. Burke B. A. Brewer S. R. Creel 《Zoo biology》1997,16(6):533-548
The purpose of this study was to validate noninvasive endocrine monitoring techniques for African wild dogs (Lycaon pictus) and to establish physiological validity of these methods by evaluating longitudinal reproductive-endocrine profiles in captive individuals. To determine the primary excretory by-products of ovarian steroid metabolism, [14C]-progesterone and [3H]-estradiol were co-administered to a female and all excreta were collected for 80 hr postinjection. Radiolabel excretion peaked ≤ 18 hr postinfusion, and progesterone and estradiol metabolites were excreted in almost equivalent proportions in urine (39.7 and 41.1%, respectively) and feces (60.3 and 58.9%, respectively). Most of the urinary metabolites were conjugated (estradiol, 94.3 ± 0.3%; progesterone, 90.4 ± 0.5%), so that immunoassays for pregnanediol-3α-glucuronide (PdG) and estrogen conjugates (EC) were effective for assessing steroid metabolites. Two immunoreactive estrogens (estradiol and estrone) and at least one immunoreactive progesterone metabolite (3α-hydroxy-5α, pregnan-20-one) were detected in feces. Urine and fecal samples were collected (1–3 times per week) for 1.5 yr from one adult female and two adult males to assess longitudinal steroid metabolite excretion. Overall correlation of urinary PdG to matched, same-day fecal progesterone metabolites immunoreactivity was 0.38 (n = 71, P < 0.05). Similarly, urinary EC was correlated (P < 0.05) with same-day fecal estrogen immunoreactivity (r = 0.49, n = 71). During pregnancy and nonpregnant cycles, copulation occurred at the time of peak (or declining) estrogen metabolites and increasing progesterone metabolites concentrations. Estrus duration was 6–9 days and gestation lasted 69 days with parturition occurring coincident with a drop in progesterone metabolites. Males exhibited seasonal trends in fecal testosterone excretion with maximal concentrations from July to September coincident with peak mating activity. Although these limited longitudinal hormone profiles should be interpreted cautiously, noninvasive gonadal steroid monitoring suggests that: (1) both female and male wild dogs may exhibit reproductive seasonality in North America, (2) females are monoestrous, and (3) peak testicular activity occurs between August and October coincident with mating behavior. From a conservation perspective, noninvasive endocrine monitoring techniques should be useful for augmenting captive breeding programs, as well as for developing an improved understanding of the physiological mechanisms underlying reproductive suppression in response to social and ecological pressures. Zoo Biol 16:533–548, 1997. © 1997 Wiley-Liss, Inc. 相似文献
6.
The survival of insect herbivores on chemically defended plants may often depend on their ability to metabolize these defense compounds. However, only little knowledge is available on how insects actually process most plant defense compounds. We investigated the metabolism of salicinoids, a major group of phenolic glycosides in poplar and willow species, by a generalist herbivore, the gypsy moth (Lymantria dispar). Seven salicinoid metabolites identified in gypsy moth caterpillar feces were mostly conjugates with glucose, cysteine or glycine. Two of the glucosides were phosphorylated, a feature not previously reported for insect metabolites of plant defense compounds. The origins of these metabolites were traced to specific moieties of three major poplar salicinoids ingested, salicin, salicortin and tremulacin. Based on the observed metabolite patterns we were able to deduce the initial steps of salicinoid breakdown in L. dispar guts, which involves cleavage of ester bonds. The conjugated molecules were effectively eliminated within 24 h after ingestion. Some of the initial breakdown products (salicin and catechol) demonstrated negative effects on insect growth and survival in bioassays on artificial diets. Gypsy moth caterpillars with prior feeding experience on salicinoid-containing poplar foliage converted salicinoids to the identified metabolites more efficiently than caterpillars pre-fed an artificial diet. The majority of the metabolites we identified were also produced by other common poplar-feeding insects. The conversion of plant defenses like salicinoids to a variety of water-soluble sugar, phosphate and amino acid conjugates and their subsequent excretion fits the general detoxification strategy found in insect herbivores and other animals. 相似文献
7.
Anne Vinther Morant Kirsten Jørgensen Bodil Jørgensen Winnie Dam Carl Erik Olsen Birger Lindberg Møller Søren Bak 《Metabolomics : Official journal of the Metabolomic Society》2007,3(3):383-398
Plants produce a plethora of secondary metabolites which constitute a wealth of potential pharmaceuticals, pro-vitamins, flavours,
fragrances, colorants and toxins as well as a source of natural pesticides. Many of these valuable compounds are only synthesized
in exotic plant species or in concentrations too low to facilitate commercialization. In some cases their presence constitutes
a health hazard and renders the crops unsuitable for consumption. Metabolic engineering is a powerful tool to alter and ameliorate
the secondary metabolite composition of crop plants and gain new desired traits. The interplay of a multitude of biosynthetic
pathways and the possibility of metabolic cross-talk combined with an incomplete understanding of the regulation of these
pathways, explain why metabolic engineering of plant secondary metabolism is still in its infancy and subject to much trial
and error. Cyanogenic glucosides are ancient defense compounds that release toxic HCN upon tissue disruption caused e.g. by
chewing insects. The committed steps of the cyanogenic glucoside biosynthetic pathway are encoded by three genes. This unique
genetic simplicity and the availability of the corresponding cDNAs have given cyanogenic glucosides pioneering status in metabolic
engineering of plant secondary metabolism. In this review, lessons learned from metabolic engineering of cyanogenic glucosides
in Arabidopsis thaliana (thale cress), Nicotiana tabacum cv Xanthi (tobacco), Manihot esculenta Crantz (cassava) and Lotus japonicus (bird’s foot trefoil) are presented. The importance of metabolic channelling of toxic intermediates as mediated by metabolon
formation in avoiding unintended metabolic cross-talk and unwanted pleiotropic effects is emphasized. Likewise, the potential
of metabolic engineering of plant secondary metabolism as a tool to elucidate, for example, the impact of secondary metabolites
on plant–insect interactions is demonstrated. 相似文献
8.
A. Lajtha H. Sershen T. Cooper A. Hashim J. Gaál Ph.D. 《Neurochemical research》1996,21(10):1155-1160
We examined the cerebral metabolism of L-deprenyl and its fluoro-derivative pF-deprenyl, assaying the parent compounds, their
metabolites desmethyl deprenyl, L-amphetamine, and L-methamphetamine, and the fluoro analogs of these metabolites. We compared
the levels of the metabolites after subcutaneous injection with those after intracerebral administration (via microdialysis)
of the parent compounds. The assay of the parent compounds and their metabolites was by GC-MS measurement of the components
of brain microdialysate samples. After their subcutaneous administration, deprenyl and F-deprenyl rapidly entered the brain
and then their concentration decreased, with an approximate half-life of 4.5 h. After the intracerebral administration the
diffusion from the site of administration was minor. A small fraction (a few percent) of the intracerebrally administered
deprenyl was metabolized in situ in the brain possibly by a nonenzymatic process. Metabolism of pF-deprenyl was somewhat more
rapid. The higher cerebral levels of metabolites after the subcutaneous administration indicate their exogenous origin—metabolism
of parent compounds in the periphery and penetration of the brain by the metabolites. 相似文献
9.
Xinru Wang Jinling Diao Zhigang Shen Wentao Zhu Ping Zhang Zhiqiang Zhou 《Chirality》2013,25(11):743-750
The stereoselective metabolism of lactofen in primary rat hepatocytes was studied using a chiral high‐performance liquid chromatographic (HPLC) method. Rac‐lactofen and its two enantiomers, S‐(+)‐ and R‐(?)‐lactofen, as well as two of its major metabolites, acifluorfen, S‐(+)‐ and R‐(?)‐desethyl lactofen, were used as substrates,. The single and joint cytotoxicity of parent compounds and the metabolites were assessed by coincubation with rat hepatocytes as target cells. Cytotoxicity was determined by the methyl tetrazolium (MTT) assay. In hepatocyte incubations, S‐(+)‐lactofen was degraded more rapidly than R‐(?)‐lactofen, and a stereospecific formation of S‐(+)‐desethyl lactofen was detected. Metabolism of lactofen to desethyl lactofen was processed with the retention of configuration, and the achiral compound, acifluorfen, was the shared metabolite generated from both S‐(+)‐ and R‐(?)‐lactofen. There was no chiral conversion of lactofen or desethyl lactofen enantiomers during the incubation. For the cytotoxicity research, the calculated EC50 values indicated that when being applied individually, the parent compound was less toxic than its metabolites, while the combination with metabolites enhanced its cytotoxic effects. The data presented here would be helpful for a more comprehensive assessment of the ecotoxicological and environmental risks of lactofen. Chirality 25:743–750, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
10.
The role of the metabolism of the entactogen 3,4-(methylenedioxy)methamphetamine (MDMA; 1b) in neurotoxic or psychopharmacologic action is widely discussed, but not yet fully understood. To prompt further investigation into the role of MDMA metabolism, six new 3,4-(difluoromethylenedioxy) analogues of MDMA (1b) were prepared and characterized. Although electronically very different, the fluoro analogues 3-5 should be sterically very similar to the non-fluorinated parent compounds. The F-atoms may prevent the formation of toxic metabolites produced via a radical pathway (Scheme 1). Different theories regarding MDMA-induced neurotoxicity are briefly reviewed and discussed. The novel compounds 3-5 may help to verify the hypothesis that MDMA-induced neurotoxicity is the result of the formation of metabolites lacking the methylenedioxy bridge. 相似文献
11.
《Critical reviews in biotechnology》2013,33(5-6):357-389
AbstractSeveral carbamate and organophosphate compounds are used to control a wide variety of insect pests, weeds, and disease-transmitting vectors. These chemicals were introduced to replace the recalcitrant and hazardous chlorinated pesticides. Although newly introduced pesticides were considered to be biodegradable, some of them are highly toxic and their residues are found in certain environments. In addition, degradation of some of the carbamates generates metabolites that are also toxic. In general, hydrolysis of the carbamate and organophosphates yields less toxic metabolites compared with the metabolites produced from oxidation. Although microorganisms capable of degrading many of these pesticides have been isolated, knowledge about the biochemical pathways and respective genes involved in the degradation is sparse. Recently, a great deal of interest in the mechanisms of biodegradation of carbamate and organophosphate compounds has been shown because (1) an efficient mineralization of the pesticides used for insect control could eliminate the problems of environmental pollution, (2) a balance between degradation and efficacy of pesticides could result in safer application and effective insect control, and (3) knowledge about the mechanisms of biodegradation could help to deal with situations leading to the generation of toxic metabolites and bioremediation of polluted environments. In addition, advances in genetic engineering and biotechnology offer great potential to exploit the degradative properties of microorganisms in order to develop bioremediation strategies and novel applications such as development of economic plants tolerant to herbicides. In this review, recent advances in the biochemical and genetic aspects of microbial degradation of carbamate and organophosphates are discussed and areas in need of further investigation identified. 相似文献
12.
Jeroen J. Jansen J. William Allwood Emma Marsden-Edwards Wim H. van der Putten Royston Goodacre Nicole M. van Dam 《Metabolomics : Official journal of the Metabolomic Society》2009,5(1):150-161
Insect herbivores by necessity have to deal with a large arsenal of plant defence metabolites. The levels of defence compounds
may be increased by insect damage. These induced plant responses may also affect the metabolism and performance of successive
insect herbivores. As the chemical nature of induced responses is largely unknown, global metabolomic analyses are a valuable
tool to gain more insight into the metabolites possibly involved in such interactions. This study analyzed the interaction
between feral cabbage (Brassica oleracea) and small cabbage white caterpillars (Pieris rapae) and how previous attacks to the plant affect the caterpillar metabolism. Because plants may be induced by shoot and root
herbivory, we compared shoot and root induction by treating the plants on either plant part with jasmonic acid. Extracts of
the plants and the caterpillars were chemically analysed using Ultra Performance Liquid Chromatography/Time of Flight Mass
Spectrometry (UPLCT/MS). The study revealed that the levels of three structurally related coumaroylquinic acids were elevated
in plants treated on the shoot. The levels of these compounds in plants and caterpillars were highly correlated: these compounds
were defined as the ‘metabolic interface’. The role of these metabolites could only be discovered using simultaneous analysis
of the plant and caterpillar metabolomes. We conclude that a metabolomics approach is useful in discovering unexpected bioactive
compounds involved in ecological interactions between plants and their herbivores and higher trophic levels. 相似文献
13.
Rodolfo Martínez-Mota Carolina Valdespino Juan Arturo Rivera Rebolledo Rupert Palme 《International journal of primatology》2008,29(5):1365-1373
Measuring fecal glucocorticoid metabolites is now a common practice to assess the stress response in primates. Nevertheless,
it is important to validate the utilized immunoassay for each primate species before the technique is applied to populations
in the wild. We determined the stress response of black howlers (Alouatta pigra) via 2 different group-specific enzyme immunoassays (EIAs). 11-oxoetiocholanolone EIAs are suited to assess the stress response
of black howlers via fecal glucocorticoid metabolites. Levels of fecal glucocorticoid metabolites increased after we applied
a stressor, i.e. anesthesia, reaching peak concentrations 24–96 h poststressor. Both basal and stress-induced fecal glucocorticoid
metabolite levels showed individual variations. The increase of fecal glucocorticoid metabolites after the stressor (paralleling
increases in serum) indicates that one can effectively measure adrenocortical activity in Alouatta pigra via these 2 enzyme immunoassays. However, it is important to consider individual variations in the excretion of fecal glucocorticoid
metabolites when planning field endocrinological research on Alouatta pigra. Fecal glucocorticoid metabolite excretion takes 1–3 d poststressor depending on the individual. Further, there is an important
individual variability in the concentrations of glucocorticoid metabolites, which might reflect differences in stress reactivity
or fecal glucocorticoid metabolite metabolism and excretion. 相似文献
14.
Oscar J. Pozo Peter Van Eenoo Koen Deventer Leen Lootens Susana Grimalt Juan V. Sancho Felix Hernndez Philip Meuleman Geert Leroux-Roels Frans T. Delbeke 《Steroids》2008,74(10-11):837-852
The applicability of LC–MS/MS in precursor ion scan mode for the detection of urinary stanozolol metabolites has been studied. The product ion at m/z 81 has been selected as specific for stanozolol metabolites without a modification in A- or N-rings and the product ions at m/z 97 and 145 for the metabolites hydroxylated in the N-ring and 4-hydroxy-stanozolol metabolites, respectively. Under these conditions, the parent drug and up to 15 metabolites were found in a positive doping test sample. The study of a sample from a chimeric uPA-SCID mouse collected after the administration of stanozolol revealed the presence of 4 additional metabolites. The information obtained from the product ion spectra was used to develop a SRM method for the detection of 19 compounds. This SRM method was applied to several doping positive samples. All the metabolites were detected in both the uPA-SCID mouse sample and positive human samples and were not detected in none of the blank samples tested; confirming the metabolic nature of all the detected compounds. In addition, the application of the SRM method to a single human excretion study revealed that one of the metabolites (4ξ,16ξ-dihydroxy-stanozolol) could be detected in negative ionization mode for a longer period than those commonly used in the screening for stanozolol misuse (3′-hydroxy-stanozolol, 16β-hydroxy-stanozolol and 4β-hydroxy-stanozolol) in doping analysis. The application of the developed approach to several positive doping samples confirmed the usefulness of this metabolite for the screening of stanozolol misuse. Finally, a tentative structure for each detected metabolite has been proposed based on the product ion spectra measured with accurate masses using UPLC–QTOF MS. 相似文献
15.
P450s in plant-insect interactions 总被引:1,自引:0,他引:1
Schuler MA 《Biochimica et biophysica acta》2011,1814(1):36-45
Cytochrome P450 monooxygenases (P450s) are integral in defining the relationships between plants and insects. Secondary metabolites produced in plants for protection against insects and other organisms are synthesized via pathways that include P450s in many different families and subfamilies. Survival of insects in the presence of toxic secondary metabolites depends on their metabolism by more limited groups of P450s. Examples of functionally characterized plant and insect P450s known to be involved in these interactions are discussed in terms of their diversities, reactivities and regulators. These and future examples, which will be uncovered as the fields of plant biology and entomology converge on this interesting area, provide much insight into the array of plant metabolites that are mainline defenses against insects, the range of insect monooxygenases that inactivate these compounds and the evolutionary processes occurring as these organisms wage daily battles with one another. Molecular perspectives on these interactions will provide the scientific community with information critical for genetic manipulation of these organisms aimed at enhancing plant resistance to insects and eliminating insect resistance to natural plant toxins and synthetic insecticides. 相似文献
16.
Michel Randriaminahy Ludger Witte Arno Kunze Victor Wray Peter Proksch 《Biochemical Systematics and Ecology》1992,20(8):711-722
Five naturally occurring chromenes from the Asteraceae including the insecticidal compounds precocene II (1) and encecalin (2) were administered to last instar larvae of Spodoptera littoralis via the food or by topical contact. Metabolites formed and excreted via the frass were analysed by GC-MS and by direct comparison with reference compounds obtained by partial synthesis. In total 28 different metabolites were identified, many of them reported here for the first time. All metabolites detected originated from phase I reactions (most probably catalysed by Cytochrom P-450-dependent monooxygenases) by hydroxylation, demethylation or reduction of the parent chromenes. The resulting metabolites can be regarded as detoxification products based on previous structure-activity studies. The increased polarity of the metabolites will furthermore facilitate their excretion by the larvae compared to the more apolar parent chromenes. The largest number of metabolites (eight for each compound) was detected following oral treatment with precocene II and encecalin respectively. 3-Monool as well as 3,4-trans-diol derivatives predominated in the frass of larvae treated with the latter compounds whereas the 6-hydroxyethyl derivatives were the major metabolites of the other chromenes investigated. The patterns of metabolites originating from precocene II or encecalin were the same following oral application or topical treatment. 相似文献
17.
Microbiological and biotechnological aspects of metabolism of carbamates and organophosphates. 总被引:8,自引:0,他引:8
Several carbamate and organophosphate compounds are used to control a wide variety of insect pests, weeds, and disease-transmitting vectors. These chemicals were introduced to replace the recalcitrant and hazardous chlorinated pesticides. Although newly introduced pesticides were considered to be biodegradable, some of them are highly toxic and their residues are found in certain environments. In addition, degradation of some of the carbamates generates metabolites that are also toxic. In general, hydrolysis of the carbamate and organophosphates yields less toxic metabolites compared with the metabolites produced from oxidation. Although microorganisms capable of degrading many of these pesticides have been isolated, knowledge about the biochemical pathways and respective genes involved in the degradation is sparse. Recently, a great deal of interest in the mechanisms of biodegradation of carbamate and organophosphate compounds has been shown because (1) an efficient mineralization of the pesticides used for insect control could eliminate the problems of environmental pollution, (2) a balance between degradation and efficacy of pesticides could result in safer application and effective insect control, and (3) knowledge about the mechanisms of biodegradation could help to deal with situations leading to the generation of toxic metabolites and bioremediation of polluted environments. In addition, advances in genetic engineering and biotechnology offer great potential to exploit the degradative properties of microorganisms in order to develop bioremediation strategies and novel applications such as development of economic plants tolerant to herbicides. In this review, recent advances in the biochemical and genetic aspects of microbial degradation of carbamate and organophosphates are discussed and areas in need of further investigation identified. 相似文献
18.
In a number of adverse drug reactions leading to hepatotoxicity drug metabolism is thought to be involved by generation of
reactive metabolites from nontoxic drugs. In this study, an in vitro assay was developed for measurement of the impact of metabolic activation of compound on the cytotoxicity toward a human
hepatic cell line. HepG2 cells were treated for 6 h with compound in the presence or absence of rat liver S9-mix, and the
viability was measured using the MTT test. The cytotoxicity of cyclophosphamide was substantially increased by S9-mix in the
presence of NADPH. Three NADPH sources were tested: NADPH (1 mmol/L) or NADPH regenerating system with either NADP+/glucose 6-phosphate (G6P) or NADP+/isocitrate. All three NADPH sources increased the cytotoxicity of cyclophosphamide to a similar extent. Eight test compounds
known to cause hepatotoxicity were tested. For these, only the cytotoxicity of diclofenac was increased by S9 enzymes when
an NADPH regenerating system was used. The increased toxicity was NADPH dependent. Reactive drug metabolites of diclofenac,
formed by NADPH-dependent metabolism, were identified by LC-MS. Furthermore, an increase in toxicity, not related to enzymatic
activity but to G6P, was observed for diclofenac and minocycline. Tacrine and amodiaquine displayed decreased toxicity with
S9-mix, and carbamazepine, phenytoin, bromfenac and troglitazone were nontoxic at all tested concentrations, with or without
S9-mix. The results show that this method, with measurement of the cytotoxicity of a compound in the presence of an extracellular
metabolizing system, may be useful in the study of cytotoxicity of drug metabolites. 相似文献
19.
Bioavailability of chlorogenic acids following acute ingestion of coffee by humans with an ileostomy 总被引:1,自引:0,他引:1
Angélique Stalmach Gary Williamson Alan Crozier 《Archives of biochemistry and biophysics》2010,501(1):98-13155
The intestinal absorption and metabolism of 385 μmol chlorogenic acids following a single intake of 200 mL of instant coffee by human volunteers with an ileostomy was investigated. HPLC-MS3 analysis of 0-24 h post-ingestion ileal effluent revealed the presence of 274 ± 28 μmol of chlorogenic acids and their metabolites accounting for 71 ± 7% of intake. Of the compounds recovered, 78% comprised parent compounds initially present in the coffee, and 22% were metabolites including free and sulfated caffeic and ferulic acids. Over a 24 h period after ingestion of the coffee, excretion of chlorogenic acid metabolites in urine accounted for 8 ± 1% of intake, the main compounds being ferulic acid-4-O-sulfate, caffeic acid-3-O-sulfate, isoferulic acid-3-O-glucuronide and dihydrocaffeic acid-3-O-sulfate. In contrast, after drinking a similar coffee, urinary excretion by humans with an intact colon corresponded to 29 ± 4% of chlorogenic acid intake [23]. This difference was due to the excretion of higher levels of dihydroferulic acid and feruloylglycine together with sulfate and glucuronide conjugates of dihydrocaffeic and dihydroferulic acids. This highlights the importance of colonic metabolism. Comparison of the data obtained in the current study with that of Stalmach et al. [23] facilitated elucidation of the pathways involved in post-ingestion metabolism of chlorogenic acids and also helped distinguish between compounds absorbed in the small and the large intestine. 相似文献
20.
The onset of biotic stress in the host plants as a result of increased insect population size leads to enhanced levels of
secondary metabolites and associated phenolic enzyme activity. Of the three host plants examined, viz.Ricinus communis (castor),Eucalyptus globulus (eucalyptus) andManihot utilissima (tapioca), castor was the host most preferred byRetithrips syriacus. Despite the fact that tapioca had the highest levels of secondary compounds, thrips infestation persisted. However, fecundity
and growth were reduced because of the relatively high levels of primary metabolites. Gallic acid was found to be the most
toxic of the phenolic acids, followed by pyrogallol, resorcinol, phloroglucinol and vanillic acid. The less toxic phenolic
acids and flavanoids were detected in leaves that harboured thrips, while the preponderance of gallic acid was found in uninfested
hosts. Thus the interaction ofRetithrips syriacus with the hosts is governed essentially by the biochemical profiles of its hosts, which tend to be altered subsequent to infestation,
thus manifesting induced resistance through enhanced production of phenolics 相似文献