Effects of glyphosate, mancozeb and their combinations on mouse neuroblastoma cells.

Pesticides-related toxicities have long been studied. Data regarding the effects of combined exposure to environmentally relevant pesticides however remain lacking. The herbicide glyphosate and the fungicide mancozeb are extensively used in agriculture.

Low level mancozeb exposure causes copper bioaccumulation in the renal cortex of rats leading to tubular injury.

Mancozeb is a widely-used, broad-spectrum contact dithiocarbamate fungicide. Dithiocarbamates are known to trans-chelate metals. This study was designed to evaluate the potential of Mancozeb to mobilize and bioaccumulate essential trace metals in various tissues.

Metabolic alterations and mitochondrial dysfunction underlie hepatocellular carcinoma cell death induced by a glycogen metabolic inhibitor.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. There is an urgent need for new targets to treat HCC due to limited treatment options and drug resistance. Many cancer cells are known to have high amount of glycogen than their tissue of origin and inhibition of glycogen catabolism induces cancer cell death by apoptosis.

Chrysin Ameliorates Cyclosporine-A-Induced Renal Fibrosis by Inhibiting TGF-β-Induced Epithelial-Mesenchymal Transition.

Cyclosporine A (CsA) is a nephrotoxicant that causes fibrosis via induction of epithelial-mesenchymal transition (EMT). The flavonoid chrysin has been reported to have anti-fibrotic activity and inhibit signaling pathways that are activated during EMT. This study investigated the nephroprotective role of chrysin in the prevention of CsA-induced renal fibrosis and elucidated a mechanism of inhibition against CsA-induced EMT in proximal tubule cells.

Comparative effects of Mancozeb and Disulfiram-induced striated muscle myopathies in Long-Evans rats.

Dithiocarbamates (DTCs) like mancozeb (MZ) and disulfiram (DS) are used throughout agriculture and medicine and have been implicated in neurotoxicity. Little research has been studied on the reported myopathies caused by these compounds. Their pathogenesis and mechanism of muscle toxicity has not been fully studied.

Dacomitinib antagonizes multidrug resistance (MDR) in cancer cells by inhibiting the efflux activity of ABCB1 and ABCG2 transporters.

The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Numerous mechanisms have been recognized that cause MDR, but one of the most important mechanisms is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, through which the efflux of various anticancer drugs against their concentration gradients is powered by ATP. In recent years, small molecular tyrosine kinase inhibitors (TKIs) have been developed for treatment in various human cancers overexpressing epidermal growth factor receptor (EGFR).

Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: and studies.

Previous reports have shown that some tyrosine kinase inhibitors (TKIs) could inhibit the ATP-binding cassette (ABC) transporters involved in multidrug resistance (MDR). Quizartinib (AC220), a potent class III receptor tyrosine kinase inhibitor (TKI), was synthesized to selectively inhibit FMS-like tyrosine kinase-3 (FLT3), a target in the treatment of acute myeloid leukemia (AML). Quizartinib is currently under clinical trials for ITD and wild-type AML and is tested in combination with chemotherapy.

Copper pyrithione, a booster biocide, induces abnormal muscle and notochord architecture in zebrafish embryogenesis.

The metal pyrithiones, principally zinc (ZnPT) and copper (CuPT), are replacing tributyltin (TBT) as antifouling agents. Zebrafish embryos were exposed within the first hour after fertilization to 12 and 64 µg/L of CuPT for 24 h. Morphological abnormalities in notochord and muscle architecture were observed at 96 h post fertilization (hpf).

The effects of copper pyrithione, an antifouling agent, on developing zebrafish embryos.

A substitute for the organotins has been the use of metal pyrithiones, principally zinc and copper (CuPT) as antifouling agents. Zebrafish, Danio rerio, embryos were exposed after fertilization to increasing concentrations of CuPT (2, 4, 8, 12, 16, 32 and 64 μg/L) for 24 h. Morphological abnormalities at 30, 96 and 120 hours post fertilization (hpf) were recorded.

Discovery and structure-activity relationship of novel 2,3-dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 inhibitors.

Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 μM).

Exposure of rat hippocampal astrocytes to Ziram increases oxidative stress.

Pesticides have been shown in several studies to be the leading candidates of environmental toxins and may contribute to the pathogenesis of several neurodegenerative diseases. Ziram (zinc-bis(dimethyldithiocarbamate)) is an agricultural dithiocarbamate fungicide that is used to treat a variety of plant diseases. In spite of their generally acknowledged low toxicity, dithiocarbamates are known to cause a wide range of neurobehavioral effects as well as neuropathological changes in the brain.

Development of Solid SEDDS, IV: Effect of Adsorbed Lipid and Surfactant on Tableting Properties and Surface Structures of Different Silicates.

Purpose: To compare six commonly available silicates for their suitability to develop tablets by adsorbing components of liquid lipid-based drug delivery systems.

Methods: The tabletability of Aerosil® 200, Sipernat® 22, Sylysia® 350, Zeopharm® 600, Neusilin® US2 and Neusilin® UFL2 were studied by compressing each silicate into tablets in the presence of 20% microcrystalline cellulose and measuring the tensile strength of tablets produced. Three components of lipid based formulations, namely, Capmul® MCM EP (glycerol monocaprylocaprate), Captex® 355 EP/NF (caprylic/capric triglycerides) and Cremophor® EL (PEG-35 castor oil), were adsorbed individually onto the silicates at 1:1 w/w, and the mixtures were then compressed into tablets.

Maneb causes pro-oxidant effects in the hippocampus of Nrf2 knockout mice.

The effects of maneb were investigated in C57BL/6 Nrf2 wildtype and knockout mice. Treated KO mice showed significant weight loss as compared to WT counterparts. ICPAAS analysis demonstrated a significant increase in manganese concentration in the tissues of treated KO mice as compared to WT.

Toxicity and bioaccumulation of the booster biocide copper pyrithione, copper 2-pyridinethiol-1-oxide, in gill tissues of Salvelinus fontinalis (brook trout).

This investigation studied the acute effects of copper pyrithione (CuPT) exposure on juvenile brook trout, Salvelinus fontinalis. Morphologic changes, copper bioaccumulation, and markers of oxidative stress in gill tissue were studied. Juvenile brook trout were treated with one of six experimental doses of CuPT (2-64 microg/L) for 2 hours.

Toxicity and bioaccumulation of the wood preservative copper dimethyldithiocarbamate in tissues of Long-Evans rats.

This study examined the toxicity and accumulation of copper in the livers and kidneys of Long-Evans rats after a subacute exposure to copper dimethyldithiocarbamate (CDCC) wood preservative. CDDC was recently introduced as an alternative to chromated copper arsenate (CCA) preserved wood. Female rats (220-270 g) were treated with 0, 25, 50, or 75 mg/kg CDDC by oral gavage for 3 wk.

The effects of the wood preservative copper dimethyldithiocarbamate in the hippocampus of maternal and newborn Long-Evans rats.

The potential toxic effects on human health and deleterious effects to the environment by copper dimethyldithiocarbamate (CDDC), an alternative wood preservative to chromated copper arsenate (CCA) have not been investigated. This study describes the neurotoxicity and accumulation of copper in the hippocampus of maternal and newborn Long-Evans rats following a subacute exposure to CDDC. Pregnant rats (220-270g) were treated daily with 0mg/kg, 25mg/kg, 50mg/kg, or 75mg/kg CDDC by oral gavage starting from day 6 of gestation and continuing to parturition.

Biodegradation behavior of gellan gum in simulated colonic media.

The objective of this investigation was to test the biodegradability of gellan gum in the presence of galactomannanase in order to explore its suitability for the development of colon-specific controlled delivery systems. Gellan beads containing azathioprine (AZA) were prepared by ionotropic gelation in the presence of Ca2+ ions and were coated with an enteric polymer, Eudragit S-100. The effects of the simulated colonic fluid (SCF, pH 7.

The role of chemically induced glutathione and glutathione S-transferase in protecting against 4-hydroxy-2-nonenal-mediated cytotoxicity in vascular smooth muscle cells.

4-Hydroxy-2-nonenal (HNE) has been suggested to contribute to the pathogenesis of atherosclerosis. One of the major metabolic transformation pathways of HNE involves conjugation with glutathione (GSH) catalyzed by GSH S-transferase (GST). In this study, we have characterized the induction of GSH and GST by 3H-1,2-dithiole-3-thione (D3T) and the protective effects of the D3T-elevated cellular defenses on HNE-mediated toxicity in rat aortic smooth muscle A10 cells.

Induction of cellular glutathione and glutathione S-transferase by 3H-1,2-dithiole-3-thione in rat aortic smooth muscle A10 cells: protection against acrolein-induced toxicity.

There is increasing evidence that aldehydes, including acrolein generated endogenously during the degradation process of biological molecules or the metabolism of foreign chemicals may be involved in the pathogenesis of cardiovascular diseases, such as atherosclerosis. Because glutathione (GSH) and GSH S-transferase (GST) are a major cellular defense against the toxic effects of reactive aldehydes, in this study we have characterized the inducibility of GSH and GST by the unique chemoprotective agent, 3H-1,2-dithiole-3-thione (D3T) and their protective effects against acrolein-induced toxicity in rat aortic smooth muscle A10 cells. Incubation of rat aortic A10 cells with micromolar concentrations of D3T resulted in a concentration- and time-dependent induction of both GSH and GST.