Age-related differences in susceptibility to toxic effects of valproic acid in rats.

A multi-age rat model was evaluated as a means to identify a potential age-related difference in liver injury following exposure to valproic acid (VPA), a known pediatric hepatotoxic agent. Different age groups of Sprague-Dawley (SD) rats (10-, 25-, 40-, 80-day-old) were administered VPA at doses of 160, 320, 500 or 650 mg kg(-1) (i.p.

Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium.

Sensitive biomarkers are needed to detect kidney injury at the earliest stages. The objective of this study was to determine whether the appearance of kidney injury molecule-1 (Kim-1) protein ectodomain in urine and kidney injury molecule-1/hepatitis A viral cellular receptor-1 (Kim-1/Havcr1) gene expression in kidney tissue may be more predictive of renal injury after exposure to nephrotoxicants when compared to traditionally used biomarkers. Male Sprague-Dawley rats were injected with a range of doses of gentamicin, mercury (Hg; HgCl2), or chromium (Cr; K2Cr2O7).

Photoreceptor cell apoptosis induced by the 2-nitroimidazole radiosensitizer, CI-1010, is mediated by p53-linked activation of caspase-3.

The nitroimidazole radiosensitizer CI-1010 ((R)-alpha-[[(2-bromoethyl)-amino]methyl]-2-nitro-1H-imidazole-1-ethanol monohydrobromide) causes selective, irreversible, retinal photoreceptor apoptosis in vivo. The mouse 661 W photoreceptor cell line was used as a neuronotypic model of CI-1010-mediated retinal degeneration. Exposure to CI-1010 for 24 h induced apoptosis in 661 W cells, as determined by ultrastructural analysis, agarose electrophoresis and analysis of TUNEL-positive nuclei.

In situ imaging of mitochondrial outer-membrane pores using atomic force microscopy.

Here we describe a technique for imaging of the outer contours of the mitochondrial membrane using atomic force microscopy, subsequent to or during a toxic or metabolic challenge. Pore formation in both glucose-challenged and 1,3-dinitrobenzene (DNB)-challenged mitochondria was observed using this technique. Our approach enables quantification of individual mitochondrial membrane pore formations.

Liquid polymer nano-PEBBLEs for Cl- analysis and biological applications.

The first nanometer scale anion sensing fluorescent spherical nanosensors, or PEBBLEs (probes encapsulated by biologically localized embedding) have been developed for the intracellular monitoring of chloride. The general scheme for the polymerization and introduction of sensing components creates a matrix that allows for the utilization of the highly selective ionophores used in poly(vinyl chloride) and poly(decyl methacrylate) ion-selective electrodes. We have demonstrated that our previously developed scheme for cation sensors can be utilized to tailoring selective submicron sensors for use in intracellular measurements of biologically relevant anions for which selective enough fluorescent probes do not exist.

CI-1010 induced opening of the mitochondrial permeability transition pore precedes oxidative stress and apoptosis in SY5Y neuroblastoma cells.

The hetero-bifunctional nitroimidazole radiosensitizer CI-1010, R-alpha-[[(2-bromoethyl)-amino]methyl]-2-nitro-1H-imidazole-1-ethanol monohydrobromide, causes selective irreversible apoptotic loss of retinal photoreceptor cells in vivo. The human neuroblastoma cell line, SH-SY5Y, was used as a neuronotypic model of CI-1010-mediated retinal degeneration. Exposure to CI-1010 for 24 h induced apoptosis in neuroblastoma cells, as determined by histopathological and ultrastructural analysis and by TUNEL technique.