Oxidative Effects of Lead in Young and Adult Fisher 344 Rats

Abstract. Lead poisoning has been extensively studied over the years. Many adverse physiological and behavioral impacts on the human body have been reported due to the entry of this heavy metal. It especially affects the neural development of children. The current study investigates the effect of lead exposure in young (1.5 months) and adult (10 months) male Fisher 344 rats. Five weeks of lead administration resulted in a profound change in the lead levels in the red blood cells (RBCs) of the young lead-exposed group (37.0 � 4.47 �g/dl) compared to the control (�1 �g/dl) and adult (27.4 � 8.38 �g/dl) lead-exposed groups. Therefore, this study confirms the fact that gastrointestinal absorption of lead in young is greater than that of adults. Furthermore, glutathione and glutathione disulfide (GSSG) levels in RBCs, liver, and brain tissues were measured to determine thiol status; malondialdehyde (MDA

Vasoactive Intestinal Peptide Receptors in Human Platelet Membrane. Characterization of Binding and Functional Activity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73096/1/j.1749-6632.1988.tb27036.x.pd

Genotype, age, genetic background, and sex influence Epha2-related cataract development in mice

Purpose: Age-related cataract is the leading cause of blindness worldwide. Variants in the EPHA2 gene increase the disease risk, and its knockout in mice causes cataract. We investigated whether age, sex, and genetic background, risk factors for age-related cataract, and Epha2 genotype influence Epha2-related cataract development in mice. Methods: Cataract development was monitored in Epha2+/+, Epha2+/−, and Epha2−/− mice (Epha2Gt(KST085)Byg) on C57BL/6J and FVB:C57BL/6J (50:50) backgrounds. Cellular architecture of lenses, endoplasmic reticulum (ER) stress, and redox state were determined using histological, molecular, and analytical techniques. Results: Epha2−/− and Epha2+/− mice on C57BL/6J background developed severe cortical cataracts by 18 and 38 weeks of age, respectively, compared to development of similar cataract significantly later in Epha2−/− mice and no cataract in Epha2+/− mice in this strain on FVB background, which was previously reported. On FVB:C57BL/6J background, Epha2−/− mice developed severe cortical cataract by 38 weeks and Epha2+/− mice exhibited mild cortical cataract up to 64 weeks of age. Progression of cataract in Epha2−/− and Epha2+/− female mice on C57BL/6J and mixed background, respectively, was slower than in matched male mice. N-cadherin and β-catenin immunolabeling showed disorganized lens fiber cells and disruption of lens architecture in Epha2−/− and Epha2+/− lenses, coinciding with development of severe cataracts. EPHA2 immunolabeling showed intracellular accumulation of the mutant EPHA2-β-galactosidase fusion protein that induced a cytoprotective ER stress response and in Epha2+/− lenses was also accompanied by glutathione redox imbalance. Conclusions: Both, Epha2−/− and Epha2+/− mice develop age-related cortical cataract; age as a function of Epha2 genotype, sex, and genetic background influence Epha2-related cataractogenesis in mice

Mineral analysis of complete dog and cat foods in the UK and compliance with European guidelines

Mineral content of complete pet food is regulated to ensure health of the companion animal population. Analysis of adherence to these regulatory guidelines has not been conducted. Here, mineral composition of complete wet (n = 97) and dry (n = 80) canine and feline pet food sold in the UK was measured to assess compliance with EU guidelines. A majority of foods complied with ≥8 of 11 guidelines (99% and 83% for dry and wet food, respectively), but many failed to provide nutritional minimum (e.g. Cu, 20% of wet food) or exceeded nutritional maximum (e.g. Se, 76% of wet food). Only 6% (6/97) of wet and 38% (30/80) of dry food were fully compliant. Some foods (20–30% of all analysed) had mineral imbalance, such as not having the recommended ratio of Ca:P (between 1:1 to 2:1). Foods with high fish content had high levels of undesirable metal elements such as arsenic. This study highlights broad non-compliance of a range of popular pet foods sold in the UK with EU guidelines (94% and 61% of wet and dry foods, respectively). If fed exclusively and over an extended period, a number of these pet foods could impact the general health of companion animals

Evaluation of the role of glutathione in the lead-induced toxicity in Saccharomyces cerevisiae

The effect of intracellular reduced glutathione (GSH) in the lead stress response of Saccharomyces cerevisiae was investigated. Yeast cells exposed to Pb, for 3 h, lost the cell proliferation capacity (viability) and decreased intracellular GSH level. The Pb-induced loss of cell viability was compared among yeast cells deficient in GSH1 (∆gsh1) or GSH2 (∆gsh2) genes and wild-type (WT) cells. When exposed to Pb, ∆gsh1 and ∆gsh2 cells did not display an increased loss of viability, compared with WT cells. However, the depletion of cellular thiols, including GSH, by treatment of WT cells with iodoacetamide (an alkylating agent, which binds covalently to thiol group), increased the loss of viability in Pb-treated cells. In contrast, GSH enrichment, due to the incubation of WT cells with amino acids mixture constituting GSH (l-glutamic acid, l-cysteine and glycine), reduced the Pb-induced loss of proliferation capacity. The obtained results suggest that intracellular GSH is involved in the defence against the Pb-induced toxicity; however, at physiological concentration, GSH seems not to be sufficient to prevent the Pb-induced loss of cell viability

Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF)

We recently reported evidence suggesting associations between urine cadmium concentrations, reflecting long-term exposure, measured in 25 female patients (relative risk = 1.41, P = 0.412) and 15 of their male partners (relative risk = 0.19, P = 0.097) and oocyte fertilization in vitro. Blood cadmium concentrations reflect more recent exposure. We here incorporate those measures into our prior data set and employ multivariable log-binomial regression models to generate hypotheses concerning the relative effects of long-term and recent cadmium exposure on oocyte fertilization in vitro. No association is indicated for blood cadmium from women and oocyte fertilization, adjusted for urine cadmium and creatinine, blood lead and mercury, age, race/ethnicity and cigarette smoking (relative risk = 0.88, P = 0.828). However, we suggest an inverse adjusted association between blood cadmium from men and oocyte fertilization (relative risk = 0.66, P = 0.143). These results suggest that consideration of long-term and recent exposures are both important for assessing the effect of partner cadmium levels on oocyte fertilization in vitro

Evaluation of Glycine max mRNA clusters

BACKGROUND: Clustering the ESTs from a large dataset representing a single species is a convenient starting point for a number of investigations into gene discovery, genome evolution, expression patterns, and alternatively spliced transcripts. Several methods have been developed to accomplish this, the most widely available being UniGene, a public domain collection of gene-oriented clusters for over 45 different species created and maintained by NCBI. The goal is for each cluster to represent a unique gene, but currently it is not known how closely the overall results represent that reality. UniGene's build procedure begins with initial mRNA clusters before joining ESTs. UniGene's results for soybean indicate a significant amount of redundancy among some sequences reported to be unique mRNAs. To establish a valid non-redundant known gene set for Glycine max we applied our algorithm to the clustering of only mRNA sequences. The mRNA dataset was run through the algorithm using two different matching stringencies. The resulting cluster compositions were compared to each other and to UniGene. Clusters exhibiting differences among the three methods were analyzed by 1) nucleotide and amino acid alignment and 2) submitting authors conclusions to determine whether members of a single cluster represented the same gene or not. RESULTS: Of the 12 clusters that were examined closely most contained examples of sequences that did not belong in the same cluster. However, neither the two stringencies of PECT nor UniGene had a significantly greater record of accuracy in placing paralogs into separate clusters. CONCLUSION: Our results reveal that, although each method produces some errors, using multiple stringencies for matching or a sequential hierarchical method of increasing stringencies can provide more reliable results and therefore allow greater confidence in the vast majority of clusters that contain only ESTs and no mRNA sequences

New insight into the effects of lead modulation on antioxidant defense mechanism and trace element concentration in rat bone

Risks of heavy metals-induced severe bone disorders generate interest to their toxicity. The present study was undertaken to monitor the biochemical and antioxidant status of bone of 30 and 80 days old male Wistar rats exposed to 5 week lead treatment. At the end of study, the rats were sacrificed, their long bone i.e. femur were excised, cleaned of soft tissue, minced and homogenized. Nucleic acid content, alkaline phosphatase, lipid peroxidation, catalase, glutathione S-transferase and superoxide dismutase were determined in bone. In both groups of treated animals lead treatment increased the production of malondialdehyde, while reducing activities of catalase, glutathione S-transferase and superoxide dismutase, indicating that it causes oxidative stress. Parallely with these effects lead significantly reduced the nucleic acid content and the activity of alkaline phosphatase, considered as biomarkers of osteoblast's function, conditions and development of bones. Moreover the concentrations of copper, zinc, iron and sodium were reduced in the excised bones. The present study indicates that the lead induced bone toxicity and its deteriorated development is the consequence of a primary oxidative stress. Our results may be helpful in understanding the modulation of biochemical parameters under lead toxicity

Glutathione Restores the Mechanism of Synaptic Plasticity in Aged Mice to That of the Adult

Glutathione (GSH), the major endogenous antioxidant produced by cells, can modulate the activity of N-methyl-D-aspartate receptors (NMDARs) through its reducing functions. During aging, an increase in oxidative stress leads to decreased levels of GSH in the brain. Concurrently, aging is characterized by calcium dysregulation, thought to underlie impairments in hippocampal NMDAR-dependent long-term potentiation (LTP), a form of synaptic plasticity thought to represent a cellular model for memory