The ultraviolet filter 3-benzylidene camphor adversely affects reproduction in fathead minnow (Pimephales promelas).
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The ultraviolet (UV) filter 3-benzylidene camphor (3BC) is used in personal care products and in a number of materials for UV protection. 3BC has been shown in vitro and in vivo in fish to be estrogenic, but possible effects on fertility and reproduction are unknown. In this study we evaluate whether 3BC affects reproduction of fish Pimephales promelas. After a preexposure period of 21 days, reproductively mature fathead minnows were exposed to increasing concentrations of 3BC for 21 days in a static-renewal procedure. Actual 3BC concentrations decreased to 23% of initial levels and median concentrations were 0.5, 3, 33, 74, and 285 microg/l. 3BC affected reproduction in a dose-dependent manner with weak effects on fecundity at 3 microg/l, a significant decrease at 74 microg/l, and a cessation of reproduction at 285 microg/l. 3BC was accumulated in fish with an average bioconcentration factor of 313 +/- 151. Dose-dependent demasculinization in secondary sex characteristics of male fish and dose-dependent induction of plasma vitellogenin occurred, which was significant at 74 microg/l and higher. 3BC had a profound and dose-dependent effect on the histology of gonads of male and female fish at 3 microg/l and higher. At 74 and 285 microg/l, oocyte and spermatocyte development was inhibited in male and female gonads. Testes of exposed males had much fewer spermatogenic cysts, and ovaries of exposed females had much fewer mature but more atretic, follicles. This study shows significant effects of the UV filter 3BC on fertility, gonadal development, and reproduction of fish after short-term exposure that may have negative consequences on the population level. (+info)
Investigation of the prostacyclin (IP) receptor antagonist RO1138452 on isolated blood vessel and platelet preparations.
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BACKGROUND AND PURPOSE: The current study examined the utility of the recently described prostacyclin (prostanoid IP) receptor antagonist RO1138452 (2-(4-(4-isopropoxybenzyl)-phenylamino) imidazoline) as a tool for classifying prostanoid receptors. EXPERIMENTAL APPROACH: pA(2) values were determined on isolated smooth muscle and platelet preparations. KEY RESULTS: RO1138452 antagonized relaxation of human pulmonary artery, guinea-pig aorta and rabbit mesenteric artery induced by the selective IP agonist cicaprost. Schild plots had slopes close to unity, generating pA(2) values of 8.20, 8.39 and 8.12 respectively. Non-surmountable antagonism was sometimes found with the higher concentrations of RO1138452, attributable to the EP(3) contractile action of cicaprost. RO1138452 did not block relaxation of guinea-pig trachea induced by the EP(2)-selective agonist butaprost. In contrast, there was a modest inhibition of butaprost-induced relaxation of human pulmonary artery by RO1138452, implying activation of both EP(2) and IP receptors by butaprost. RO1138452 did not affect relaxation induced by PGE(2) (EP(4) agonist) and substance P (NK(1)/endothelium-dependent agonist) in rabbit mesenteric artery. In human and rat platelet-rich plasmas, RO1138452 antagonized cicaprost-induced inhibition of platelet aggregation in a surmountable manner; pA(2) values may have been affected by binding of RO1138452 to plasma protein. RO1138452 did not affect the inhibitory actions of PGD(2) (DP(1) agonist) and NECA (adenosine A(2A) agonist) in human platelets. CONCLUSIONS AND IMPLICATIONS: The data indicate that RO1138452 is a potent and selective IP receptor antagonist. RO1138452 represents an important addition to our armoury of prostanoid receptor antagonists and a potential clinical agent in situations where prostacyclin has a pathophysiological function. (+info)
Evidence against an involvement of cyclic nucleotides in the induction of betacyanin synthesis by cytokinins.
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1. A wide range of purine bases, nucleosides and cyclic nucleotides were shown to induce betacyanin synthesis in Amaranthus seedlings. 2. The induction of pigment by benzyladenine, dibutyryl cyclic AMP or cyclic AMP was not potentiated by aminophylline. Aminophylline was shown to inhibit Amaranthus cyclic AMP phosphodiesterase activity. 4. Incubation of seedlings with aminophylline inhibited the conversion of 6-[G--3H]benzyladenine into presumed 9- and 7-glucosylbenzyladenine. 5. Induction of betacyanin synthesis by 6-benzyladenine or by exposure to red light was not accompanied by changes in the total cyclic AMP content in seedlings. 6. It is concluded that the inducers tested act as cytokinin analogues; no evidence was obtained to support cyclic AMP as an intermediate in the induction process. (+info)
4-(4'-Methyltetrafluorophenyl)-2,3,5,6-tetrafluorobenzyl bromide: a new electrophoric derivatizing reagent.
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Commercially-available 4,4'-dimethyloctafluorobiphenyl was converted in a single step to 4-(4'-methyltetrafluorophenyl)-2,3,5,6-tetrafluorobenzyl bromide (MTFP-TFBBr) for the purpose of providing a new electrophoric derivatizing reagent. When reacted with this reagent, 2-fluoro-O6-(2'-hydroxyethyl)hypoxanthine, a model analyte, gave a mixture of isomeric products (apparently substituted at N7 and N9, analogous to its known reaction with pentafluorobenzyl bromide), and 53 femtograms of the mixture was detected at S/N = 10 by gas chromatography electron capture mass spectrometry (GC-EC-MS). As intended, the volatility of the MTFB-TFBBr derivative was much less (two-fold) than that of the corresponding pentafluorobenzyl derivative. It is anticipated that MTFB-TFBBr sometimes will be useful in providing an electrophoric derivative that encounters less background noise in analysis by electrophore derivatization/GC-EC-MS. (+info)
Mitochondrial thioltransferase (glutaredoxin 2) has GSH-dependent and thioredoxin reductase-dependent peroxidase activities in vitro and in lens epithelial cells.
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Thioltransferase (or Grx) belongs to the oxidoreductase family and is known to regulate redox homeostasis in cells. Mitochondrial Grx2 is a recent discovery, but its function is largely unknown. In this study we investigate Grx2 function by examining its potential peroxidase activity using lens epithelial cells (LEC). cDNA for human and mouse Grx2 was cloned into pET21d(+) vector and used to produce respective recombinant Grx2 for kinetic studies. cDNA for human Grx2 was transfected into human LEC and used for in vivo studies. Both human and mouse Grx2 showed glutathione (GSH)-dependent and thioredoxin reductase (TR)-dependent peroxidase activity. The catalytic efficiency of human and mouse Grx2 was lower than that of glutathione peroxidases (2.5 and 0.8x10(4) s(-1) M(-1), respectively), but comparable with TR-dependent peroxiredoxins (16.5 and 2.7x10(4) s(-1) M(-1), respectively). TR-dependent peroxidase activity increased 2-fold in the transfected cells and was completely abolished by addition of anti-Grx2 antibody (Ab). Flow cytometry (FACS) analysis and confocal microscopy revealed that cells preloaded with pure Grx2 detoxified peroxides more efficiently. Grx2 over-expression protected cells against H2O2-mediated disruption of mitochondrial transmembrane potential. These results suggest that Grx2 has a novel function as a peroxidase, accepting electrons both from GSH and TR. This unique property may play a role in protecting the mitochondria from oxidative damage. (+info)
Aerobic oxidation of benzyl- and allylic alcohols under visible light irradiation of a fluorescent lamp in the presence of catalytic iodine.
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Benzyl alcohols and allylic alcohols were found to be oxidized to the corresponding aldehydes in the presence of a catalytic amount of iodine under irradiation of a fluorescent lamp. (+info)
Effect of synthetic matrix metalloproteinase inhibitors on lipopolysaccharide-induced blood-brain barrier opening in rodents: Differences in response based on strains and solvents.
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Matrix metalloproteinase inhibitors (MMPIs) reduce blood-brain barrier (BBB) disruption and prevent cell death. Animal models of multiple sclerosis, cerebral ischemia and hemorrhage, and bacterial meningitis respond to treatment with MMPIs. We have used the intracerebral injection of lipopolysaccharide (LPS) in rat, which induces MMP production and results in a delayed opening of the BBB, to screen MMPIs to identify therapeutic agents. We hypothesized that the mouse would respond similarly to LPS and that the mouse/LPS model of BBB damage would be more useful for screening of MMPIs. Therefore, we adapted the rat LPS model to the mouse and compared the response to LPS and treatment with MMPIs. Wistar-Kyoto rats (WKY) and three strains of mice had stereotactic injections of LPS into the caudate. (14)C-sucrose was used to measure permeability of the BBB 24 h after injection. Initially, we tested three broad-spectrum MMPIs in the rat, BB-1101, BB-94, and BB-2293, and a MMP-2 selective inhibitor, IW449; both BB-1101 and BB-94 significantly suppressed LPS-induced BBB damage (p<0.05). In the 3 mouse strains, C57/BL6, C57/BL10, and C57/BL10HIIIR2, LPS significantly opened the BBB in C57/BL6, and it was the only strain that showed a reduction in BBB permeability with BB-94. Treatment with methylprednisolone and several broad-spectrum MMPIs, including BB-1101, was ineffective in the C57/BL6. There was a significant reduction in BBB permeability seen with 10% dimethyl sulfoxide (DMSO) alone, which was used to dissolve the selective MMP-2 and-9 inhibitor, SB-3CT. The tetracycline derivative, minocycline, reduced the BBB injury in mouse by blocking the production of MMP-9. Our results show variability in rats and mice to LPS and MMPIs, which most likely is based on genetic make-up. Understanding these differences may provide important clues that could guide selection of MMPIs in treatment of neurological diseases. (+info)
Protective effect of (4-methoxybenzylidene)-(3-methoxynophenyl)amine against neuronal cell death induced by oxygen and glucose deprivation in rat organotypic hippocampal slice culture.
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Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural phytoalexin found in grape skin, and has been suggested to be an antioxidant agent, an anticancer agent and a cardioprotective agent. In particular, recent experimental evidence has demonstrated that resveratrol exhibits neuroprotective effects in various assay systems. During the study on the resveratrol derivatives, we found that (4-methoxybenzylidene)-(3-methoxyphenyl)amine (MBMPA), which has blocked free phenolic groups, strongly protects neuronal cells against ischemic damage on a higher activity than resveratrol. The MBMPA potently reduced the level of neuronal cell death in an oxygen and glucose deprivation-exposed rat organotypic hippocampal slice culture. In addition, ATP depletion following the onset of oxygen and glucose deprivation in an adult hippocampal slice was blocked by the MBMPA treatment. These results suggest that MBMPA has a neuroprotective effect on an in vitro ischemia model, and may be useful for treating stroke. (+info)