Journal of biochemical toxicology最新文献

{"title":"Mechanism of inhibition of rat brain (Na+-K+)-stimulated adenosine triphosphatase reaction by cadmium and methyl mercury.","authors":"K I Ahammadsahib,&nbsp;R Ramamurthi,&nbsp;D Dusaiah","doi":"10.1002/jbt.2570020303","DOIUrl":"https://doi.org/10.1002/jbt.2570020303","url":null,"abstract":"<p><p>The mechanisms of inhibition of rat brain Na+-K+-ATPase by cadmium chloride (CdCl2) and methylmercuric chloride (CH3HgCl) were studied in vitro by assessing the effects of these heavy metals on this enzyme and associated component parameters. Both the heavy metals significantly inhibited the overall Na+-K+-ATPase in a concentration-dependent manner with an estimated median inhibitory concentration (IC-50) of 3.2 X 10(-5) M for CdCl2 and 6 X 10(-6) M for CH3HgCl. Protection of enzyme against heavy metal inhibition by 5 X 10(-5) M to 1 X 10(-4) M dithiothreitol (DTT) and glutathione (GSH) or cysteine (CST) indicates that both monothiols and dithiols have the same ability in regenerating sulfhydryl (-SH) groups or chelating the metals. Inhibition of K+-p-nitrophenyl phosphatase (K+-PNPPase), the component enzyme catalyzing the K+-dependent dephosphorylation in the overall Na+-K+-ATPase reaction by these heavy metals, indicates that the mechanism of inhibition involves binding to this phosphatase. Reversal of K+-PNPPase inhibition by DTT, GSH, and CST suggests sulfhydryl groups as binding sites. Binding of 3H-ouabain, a cardiac glycocide and inhibitor of both phosphorylation and dephosphorylation, to brain fraction was significantly decreased by CH3HgCl, and this inhibition was reversed by the three thiol compounds, suggesting presence of -SH group(s) in the ouabain receptor site. Cadmium chloride failed to inhibit the binding of this receptor, indicating that the mechanics of inhibition of ATPase by CH3HgCl and CdCl2 are different from each other. The results suggest that the critical conformational property of enzyme common to both kinase (E1) and phosphatase (E2) is susceptible to CH3HgCl whereas only phosphatase is sensitive to CdCl2.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"2 ","pages":"169-80"},"PeriodicalIF":0.0,"publicationDate":"1987-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570020303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13992388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuation of 2-methoxyethanol and methoxyacetic acid-induced digit malformations in mice by simple physiological compounds: implications for the role of further metabolism of methoxyacetic acid in developmental toxicity.","authors":"F Welsch,&nbsp;R B Sleet,&nbsp;J A Greene","doi":"10.1002/jbt.2570020307","DOIUrl":"https://doi.org/10.1002/jbt.2570020307","url":null,"abstract":"<p><p>The ethylene glycol ether 2-methoxyethanol (ME) and its oxidation product methoxyacetic acid (MAA) are selective embryotoxins and equipotent as inducers of digit malformations when given by gavage to pregnant Crl:CD-1 ICR BR mice on gestation day 11. Earlier observations showed that the teratogenic effects were attenuated by delayed administrations of ethanol given at a time when all ME is already converted to MAA. That outcome suggested that acetate from ethanol catabolism might compete with methoxy-acetate in biosynthetic reactions relevant to MAA-induced malformations. Furthermore, 14C derived from [1,2-14C]-ME or [1-14C]-MAA is incorporated into all macromolecular fractions of the embryo, and 14C is exhaled by the dam in 14CO2. Those data indicate that 14C derived from 14C-ME catabolism enters into many metabolic reactions. The present study examined acetate and other simple physiological compounds with close relationships to carbon and one-carbon moiety metabolic pathways for their ability to attenuate digit malformations upon concomitant dosing with ME. All of the agents examined reduced the teratogenic effect significantly with a potency rank order of formate much greater than acetate = glycine much greater than D-glucose. The common link for their efficacy may be the one-carbon moiety oxidation pathway that involves tetrahydrofolic acid as a catalyst of one-carbon transfer into purines and thymidylate. Carbon from all of the attenuators administered is incorporated into those bases and then into DNA. It appears as if methoxyacetate enters into biochemical reactions analogous to those of acetate. This speculation is supported by the metabolic fate of 14C from 14C-ME in dam and embryo. Based on the indirect evidence obtained with all of the simple compounds that attenuate the ME-induced digit malformations, we postulate that abnormal macromolecules are generated by anabolic reactions and that those products disrupt normal paw development.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"2 ","pages":"225-40"},"PeriodicalIF":0.0,"publicationDate":"1987-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570020307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14630647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of metal cations on pituitary hormone secretion in vitro.","authors":"R L Cooper,&nbsp;J M Goldman,&nbsp;G L Rehnberg,&nbsp;W K McElroy,&nbsp;J F Hein","doi":"10.1002/jbt.2570020308","DOIUrl":"https://doi.org/10.1002/jbt.2570020308","url":null,"abstract":"<p><p>Increased body burdens of metal cations are known to affect adversely reproductive function in several species. The effects of these metals on gonadal function are well documented. In contrast, little is known about their possible direct effects on pituitary hormone release. The purpose of this study was to determine, in vitro, the effects of nickel, cadmium, and zinc (50 microM) on both baseline and potassium chloride (KCl)-stimulated pituitary luteinizing hormone (LH), prolactin (Prl), and thyroid-stimulating hormone (TSH) release. Anterior pituitary fragments from adult male Long-Evans rats were evaluated using a continuous-flow perifusion system. Baseline and stimulated LH releases were unaffected by nickel and zinc; however, cadmium caused an increase in baseline LH secretion. Baseline Prl release was decreased by zinc, while cadmium resulted in increased release of this hormone. Stimulated Prl release was lower during exposure to zinc but unaltered by nickel and cadmium. Following exposure to zinc, a rebound in stimulated release was noted for all three hormones measured. These results showed that the metal cations tested did have a direct effect on pituitary hormone release at a dose lower than those reported to alter testicular function in vitro. Furthermore, the changes in pituitary hormone secretion varied depending upon the metal and hormone being evaluated.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"2 ","pages":"241-9"},"PeriodicalIF":0.0,"publicationDate":"1987-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570020308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14630649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gentamicin-induced alterations in phospholipid metabolism in cultured human proximal tubular cells.","authors":"S Chatterjee","doi":"10.1002/jbt.2570020304","DOIUrl":"https://doi.org/10.1002/jbt.2570020304","url":null,"abstract":"<p><p>The effects of gentamicin on phospholipid levels and metabolism and the uptake of phosphatidylcholine (PC) adsorbed to low-density lipoprotein (LDL) were investigated in cultured human proximal tubular (PT) cells. Cells incubated with gentamicin (0.3 mM) for one to 21 days had a similar increase in the cell number and protein as compared to control cells. However, the cellular levels of phosphatidylcholine (PC) and sphingomyelin (SM), but not other phospholipids, increased in a time-dependent manner. Incubation of gentamicin (0.3 to 3.0 mM) resulted in a concentration-dependent increase in the cellular levels of PC (50% to 320%) and SM (20% to 40%). Gentamicin stimulated the incorporation of [14C]-acetate into diacylglycerol, PC, and SM in the order of 300%, 66%, and 20%, respectively, but not into lysophosphatidylcholine (LPC). Similarly, gentamicin stimulated the incorporation of [14C]-choline into PC and SM in the order of 300% and 172%, respectively, but not into LPC as compared to control cells. In addition, gentamicin also stimulated the incorporation of [14C]-choline into cytidine diphosphocholine (CDP-choline). However, the endocytosis of [14C]-PC-LDL was lower in cells incubated with gentamicin than in control cells. Thus, exogenously derived PC on LDL does not contribute to the increased cellular levels of PC in PT cells incubated with gentamicin. The activity of cytidine triphosphate (CTP):phosphocholine cytidyltransferase was moderately lower in cells incubated with gentamicin as compared to control. By contrast, the activity of phospholipase A1 and phospholipase C was twofold lower in cells incubated with gentamicin for 21 days as compared to control. Thus, increased incorporation of [14C]-acetate and [14C]-choline into PC in cells incubated with gentamicin may not only be due to increased endogenous synthesis but to decreased catabolism of newly synthesized PC. We conclude that gentamicin impairs the lysosomal catabolism of PC, leading to its accumulation in PT cells. This phenomenon may be an indication of gentamicin-induced nephrotoxicity in man.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"2 ","pages":"181-201"},"PeriodicalIF":0.0,"publicationDate":"1987-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570020304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13992390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral glucose and glycogen metabolism in diazinon-treated animals.","authors":"M A Matin,&nbsp;K Husain","doi":"10.1002/jbt.2570020310","DOIUrl":"https://doi.org/10.1002/jbt.2570020310","url":null,"abstract":"<p><p>The intraperitoneal (IP) treatment of rats with diazinon (40 mg/kg) resulted in a variety of changes in the brain. Glycogen was depleted, but there was an increase in the activities of glycogen phosphorylase, phosphoglucomutase, hexokinase, lactate dehydrogenase, and fructose 1,6 diphosphatase. The activity of glucose-6-phosphatase was unaffected while that of cholinesterase was significantly reduced. Lactic acid content was increased, while that of pyruvate was not altered. Animals developed tremors and convulsions, which were maximal two hours after treatment. The induced changes may be compensatory mechanisms to provide extra energy to cerebral tissue as a result of the stimulatory effects in diazinon-treated animals.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"2 ","pages":"265-70"},"PeriodicalIF":0.0,"publicationDate":"1987-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570020310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14631786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age and growth-related changes in cyclopiazonic acid-potentiated lipophilic cation accumulation by cultured cells and binding to freeze-thaw lysed cells.","authors":"R T Riley,&nbsp;D E Goeger,&nbsp;W P Norred,&nbsp;R J Cole,&nbsp;J W Dorner","doi":"10.1002/jbt.2570020309","DOIUrl":"https://doi.org/10.1002/jbt.2570020309","url":null,"abstract":"<p><p>In a previous study (1) we demonstrated that increased tetraphenylphosphonium (TPP) uptake by renal epithelial cells (LLC-PK1) exposed to the fungal metabolite cyclopiazonic acid (CPA) was not a result of hyperpolarization across the plasma membrane even though CPA-potentiated TPP uptake could be totally inhibited by the depolarizing agent carbonylcyanide-m-chlorophenylhydrazone (CCCP). We now demonstrate that CPA potentiates TPP accumulation by proliferating skeletal muscle (L6) and LLC-PK1 cells but not by nonproliferating primary rat hepatocytes. In LLC-PK1 cells, CPA-potentiated TPP accumulation is observed in cells at all ages. In L6 cells, CPA-potentiated TPP accumulation is maximal soon after subculturing, and as the cells age they become less sensitive to CPA until TPP accumulation by CPA-treated cells approaches that of untreated cells. The temporal change in sensitivity of L6 cells to CPA may be related to biochemical and/or metabolic changes which occur as the cells age in culture. Hepatocytes, LLC-PK1 cells, and L6 cells permeabilized by freeze-thaw lysis, all exhibit CPA-potentiated TPP partitioning, even in the presence of CCCP. This result indicates that both TPP and CPA must have access to the intracellular space in order for potentiated TPP partitioning to be observed. We hypothesize that the site of interaction between CPA and TPP is intracellular and probably associated with the cytoplasmic side of the plasma membrane and possibly the mitochondria.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"2 ","pages":"251-64"},"PeriodicalIF":0.0,"publicationDate":"1987-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570020309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14631784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of single-strand breaks and interstrand cross-links in liver DNA after the administration of 2-acetylaminofluorene and trans-4-acetylaminostilbene to rats.","authors":"M Ruthsatz,&nbsp;H G Neumann","doi":"10.1002/jbt.2570020311","DOIUrl":"https://doi.org/10.1002/jbt.2570020311","url":null,"abstract":"<p><p>2-Acetylaminofluorene (AAF) or trans-4-acetylaminostilbene (AAS) was orally or intraperitoneally administered to female Wistar rats. DNA from liver cells was analyzed for single-strand breaks by the alkaline elution assay. Only borderline effects were observed with doses (100 mumol/kg) used in animal carcinogenesis experiments. Even high doses of AAF (1,000 mumol/kg) were not effective. Methyl methanesulfonate (MMS) in vivo and gamma irradiation in vitro were shown to produce dose-dependent DNA single-strand breaks (positive control). Only a marginal effect was obtained with 100 mumol/kg MMS. The elution rate of DNA was increased by a factor of 34 in liver cells in vitro with 400 rad of gamma irradiation. Only a fraction of this rate could be demonstrated immediately after irradiation in vivo, and no lesions were found two hours later. This strongly indicates the rapid repair of single-strand breaks. Additional experiments showed that AAS, a nonhepatocarcinogen, produced more interstrand cross-links in the rat liver DNA than did AAF.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"2 ","pages":"271-9"},"PeriodicalIF":0.0,"publicationDate":"1987-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570020311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14631787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allylisopropylacetamide induces rat hepatic ornithine decarboxylase.","authors":"K T Kitchin,&nbsp;J L Brown","doi":"10.1002/jbt.2570020306","DOIUrl":"https://doi.org/10.1002/jbt.2570020306","url":null,"abstract":"<p><p>In rat liver, allylisopropylacetamide (AIA) treatment strongly induced (25-fold) the activity of rat hepatic ornithine decarboxylase (ODC). By either the oral or the subcutaneous route, AIA produced a long-lasting induction (30 to 40 hours) of hepatic ODC activity. Three analogs of AIA, propylisopropylacetamide (PIA), allobarbital, and allylbenzene, were active ODC inducers while a fourth, allylacetate, was not. Although induction of hepatic aminolevulinic acid (ALA) synthetase activity and the accumulation of hepatic porphyrins depend on the allyl moiety of AIA, this is not the case with hepatic ODC induction. Allylisopropylacetamide did not elevate serum alanine aminotransferase (SGPT) nor did it cause DNA damage, as measured by the alkaline elution assay. Thus, hepatic cell death is not a likely explanation of AIA's long-lasting induction of ODC. As AIA does not belong to any of the common categories of ODC inducers, it may be the chemical prototype of a new class of hepatic ODC inducers.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"2 ","pages":"215-23"},"PeriodicalIF":0.0,"publicationDate":"1987-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570020306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14630646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo and in vitro synthesis, release, and uptake of [3-H]-dopamine in mouse striatal slices after in vivo exposure to chlordecone.","authors":"K Fujimori,&nbsp;H Benet,&nbsp;H M Mehendale,&nbsp;I K Ho","doi":"10.1002/jbt.2570010402","DOIUrl":"https://doi.org/10.1002/jbt.2570010402","url":null,"abstract":"<p><p>Effects of treatment of mice with chlordecone (25 mg/kg/d) on striatal dopaminergic activities such as synthesis, turnover, uptake, and release were investigated in vivo and in vitro. In mice receiving chlordecone for five days, there were no significant changes in in vivo dopamine (DA) synthesis and turnover in striatum and in vitro [3-H]-dopamine uptake and K+-stimulated [3-H]-dopamine release in striatal slices. In mice receiving chlordecone for eight days, the in vivo synthesis of [3-H]-dopamine from [3-H]-tyrosine in striatum was slightly inhibited and the in vitro [3-H]-dopamine synthesis in striatal slices was significantly decreased. Furthermore, both uptake and K+-stimulated release of [3-H]-dopamine from striatal slices were significantly reduced. The turnover rate of newly synthesized [3-H]-dopamine from [3-H]-tyrosine in striatal slices was unchanged after eight consecutive days of chlordecone administration. These results suggest that chlordecone may cause impairments in pre- and/or postsynaptic membranes of dopaminergic neurons which modulate motor function.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"1 4","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570010402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13630246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peroxidase, an alternate pathway to cytochrome P-450 for xenobiotic metabolism in skin: partial purification and properties of the enzyme from neonatal rat skin.","authors":"B H Strohm,&nbsp;A P Kulkarni","doi":"10.1002/jbt.2570010408","DOIUrl":"https://doi.org/10.1002/jbt.2570010408","url":null,"abstract":"<p><p>Peroxidase activity was partially purified from neonatal (3 to 6 days old) rat skin. The membrane-bound peroxidase activity was extracted with 0.5 M calcium chloride and was monitored spectrophotometrically at 470 nm with 2-methoxyphenol (guaiacol) and hydrogen peroxide as substrates. Subcellular distribution studies indicated the activity to be highest and comparable in nuclei and mitochondria, lowest in microsomes, and absent in cytosol. The peroxidase activity was partially purified by affinity chromatography on concanavalin A-sepharose 4B and by gel filtration using Bio-Gel P-150. Purification factors from these two steps were about 25 and 4, respectively. Peroxidase extraction in the presence of 2 mM N-ethylmaleimide increased activity about twofold. The combination of 2 mM N-ethylmaleimide and 10% (w/v) glycerol was found to be optimal for preservation of activity. Peroxidase activity increased linearly with increases in protein concentration, time, and guaiacol concentration. Activity was inhibited approximately 75% by 0.1 mM potassium cyanide or 0.05 mM sodium azide. Pyrogallol, hydroquinone, p-cresol, catechol, benzidine, 3,3'-dimethoxybenzidine, tetramethylbenzidine and p-phenylenediamine also acted as substrates for the rat cutaneous peroxidase.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"1 4","pages":"83-97"},"PeriodicalIF":0.0,"publicationDate":"1986-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570010408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13992890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}