摘要:

AbstractThe toxicokinetics and biotransformation of pentachlorophenol (PCP) were determined in the topsmelt (Atherinops affinis) In a static system, topsmelt (n= 9) were exposed to 50 μg/L of [U‐14C]PCP for 24 hours to determine the absorption rate constant (Ka), the whole‐body bio‐concentration (at steady‐state conditions), the elimination rate constant UQ, and the elimination half‐life (t1/2). Kinetics were determined by direct quantitation of radioactivity in the exposure water. Following exposure, fish were placed in a flow‐through metabolism chamber for 24 hours to allow depuration of retained residues, which were collected on XAD‐4 resin. Excreted residues were identified and quantified by high‐pressure liquid co‐chromatography, fraction collection, and liquid scintillation counting. The Kaand Ke, calculated using a simplified model, were 0.012 M‐1 0.005/h and 0.014±;0.003/h, respectively, while the 24 hour total concentration factor was 278.0×182.0 and thet1/2was 52.7±;11.2. During 24 hours of exposure to dean seawater, topsmelt depurated 32.9% of retained residues, and while PCP was primarily excreted unchanged (64.9%), significant amounts of both pentachlorophenylsulfate (18.9%) and pentachloro‐β‐D‐glucur

ISSN:0887-2082    

DOI:10.1002/jbt.2570080302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe have studied the effects of short‐term exposure of guinea pigs to cigarette smoke under both mainstream (MS) and sidestream (SS) conditions on the activities of major antioxidant enzymes and lipid peroxidation potential of erythrocytes. The smoke‐exposed groups had an increase in the activity of superoxide dismutase (SOD), a decrease in the activities of glutathione peroxidase (GSH‐Px) and NADPH generating enzymes, and no change in the activity of catalase. Furthermore, there was a significant increase in the in vitro lipid peroxidation potential of erythrocytes in both MS‐ and SS‐exposed groups. However, the lipid peroxidation potential was higher in the MS‐exposed group than that in the SS‐

ISSN:0887-2082    

DOI:10.1002/jbt.2570080303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe clonal insulin producing cell line RINmSF was evaluated as a model for the action of cyproheptadine (CPH)‐like diabetogenic com pounds in the rat pancreas. Treatment with 10 μM CPH and selected structural analogs under culture conditions produced a progressive loss of cellular insulin which reached 30% of control within 24 hours. Comparison of the activities of the analogs 4‐diphenylmethylpiperidine (4‐DPMP) and 2‐di‐phenylmethylpiperidine (2‐DFMP) to produce cellular insulin depletion showed that 4‐DPMP was as active as CPH but 2‐DPMP had no activity at the highest concentration employed (10 μM). The CPH metabolite desmethyl CPH‐epoxide was five times more active than the parent compound in producing loss of insulin in RINm5F cells. These results are consistent with previously published results of CPH actions in vivo. An inhibition of insulin biosynthesis with no loss of preproinsulin mRNA occurred in RINm5F cells treated with CPH or DMCPH‐epoxide. This suggests that an effect on transcription may not be the primary action by which CPH and its analogs inhibit insu

ISSN:0887-2082    

DOI:10.1002/jbt.2570080304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractA polyclonal antibody was made to a liver cytochrome P450 purified from di‐(2‐ethyl‐hexy)Dphthalate (DEHP)‐treated Sprague‐Dawley rats and was used to identify the CYP4A forms in liver and kidney cortex microsomes of control rats and rats treated with this peroxisome proliferator. Three clearly separated major protein bands were recognized on western blots in liver microsomes of control male rats or male rats treated with a single dose of DEHP, which, based on the description of relative mobility, tissue specificity, and sex dependent expression of CYP4A forms (Sundseth and Waxman (1992).J. Biol. Chem., 267, 801–810), correspond to the migration pattern of forms 4A1, 4A2, and 4A3 in clofibrate‐treated rats. The administration of DEHP for 2 or 3 days caused a loss of resolution of two of the protein bands. The protein band corresponding to 4A2 was absent in liver or kidney cortex microsomes of DEHP‐treated or control female rats and was not always visible in the livers of control male rats. The purified P450DEHPsupported the hydroxylation of arachidonic acid at both the 19‐ and 20‐carbon atoms with turnover rates of 1.4×0.2 and 22.7×2.5 nmoles per minute per nmol P450, respectively. No measurable amounts of hydroxylated products were obtained when prostaglandin E1, leukotriene B4, or testosterone were used as substrates. Another member of the CYP4 family, 4B1 from rabbit lung microsomes, was also recognized by this antibody on western blot analysis; however, rabbit lung form 4A4 showed only minimal cross‐reacti

ISSN:0887-2082    

DOI:10.1002/jbt.2570080305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe toxicity of ricin in susceptible cells is well characterized biochemically, but the pathophysiological implications of its toxicity and the immune response to ricin challenge in the lung are unknown. Incubating macrophage cell line with ricin (1 pM‐10 nM) for 4 hours markedly inhibited3H‐leucine incorporation (acid insoluble) into protein (>95%, at 1 nM) without affecting the acid‐soluble radioactivity. In spite of increased uptake of total thymidine (141×13.5%) and total uridine (135×17.2%), DNA synthesis in ricin‐treated cells was progressively inhibited although RNA synthesis was not affected. Fluocinolone (an anti‐inflammatory glucocorticoid) pretreatment increased the ricin‐induced inhibition of protein synthesis. The synergistic effect of fluocinolone on ricin‐induced protein synthesis inhibition was due to an increased binding (167%,p<0.01) and internalization (134×12%, p<0.025) of ricin. Partial protection from ricin‐induced inhibition of protein synthesis by indomethacin (nonsteroidal, anti‐inflammatory agent) was due to decreased binding and internalization of ricin. These results show that macrophages are sensitive to ricin and that pharmacologically active drugs may regulate ricin's toxicity, perhaps by controlling synthesis and release of certain med

ISSN:0887-2082    

DOI:10.1002/jbt.2570080306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractChlorinated acetaldehydes have been the focus of research due to their role as reactive intermediates and their possible occurrence in chlorinated drinking water. This study investigated the in vitro substrate specificity of cytosolic and mitochondrial rat liver aldehyde dehydrogenase toward these compounds. Monochloroacetaldehyde was found to be extensively metabolized by these enzymes, to an even greater extent than the standard substrate propionaldehyde. Dichloroacetaldehyde was metabolized to a much lesser extent, and chloral hydrate is not metabolized by this enzyme family. TheKmM (mM) andVmax(Vmaxfor propionaldehyde set to 100) values with the lowKmcytosolic enzyme were monochloroacetalde‐hyde 0.046. and 582, and dichloroacetaldehyde 0.13 and 54.9, and those with the high Kmcytosolic en zyme were dichloroacetaldehyde 0.35 and 23.4. The values with the lowKmmitochondrial enzyme were monochloroacetaldehyde 0.057 and 462 and dich loroacetaldehyde 0.038 and 12.9, and those with the highKmmitochondrial enzyme were monochloroacetaldehyde 0.024 and 55.5 and dichloroacetaldehyde 0.29 and 3.44. These data suggest that aldehyde dehydrogenase plays a significant role in the metabolism of monochloroacetaldehyde and, to some extent, dichloroacetaldehyde. Some evidence also suggested that alcohol dehydrogenase plays a significant role in the metabolism of dich loroacetaldehyde and chloral hydrat

ISSN:0887-2082    

DOI:10.1002/jbt.2570080307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractA diisopropyl‐fluorophosphatase (DFPase) was purified from brain and ganglia of squidTodarodes pacificus steenstrup.The DFPase had a preference in hydrolysis toward diisopropylphosphorofluoridate (DFP). It also was able to hydrolyze O‐1,2,2‐trimethylpropyl methylphosphofluoridate (soman) and O‐isopropyl methylphosphonofluoridate (sarin) at nearly equal hydrolytic rates but only 1/10 that of DFP. The hydrolytic activity toward diethyl‐p‐nitrophenylphosphate (paraoxon) was very low compared with DFP, so man, and sarin. The DFPase was purified 330‐fold to a specific activity of 18,300 n mol/min/mg protein. Its molecular weight was 34,000 dalton determined by gel‐filtration chromatography. Mn2+stimulation of the DFPase was not observed when DFP and soman were the substrates, but with sarin, the rate increased onefold in the presence of 1.0 mM of Mn2+. Ethylenediamine tetraacetic acid disodium (EDTA‐Na2) at 0.05 M inhibited the DFPase activity about 30%. It could be concluded that this DFPase belongs to the

ISSN:0887-2082    

DOI:10.1002/jbt.2570080308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0887-2082    

DOI:10.1002/jbt.2570080301

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY