Determination of blood indices of albino rats treated with aluminum chloride and investigation of antioxidant effects of vitamin E and C

Abstract The current study aims to investigate hematological and biochemical blood indices of albino rats administrated aluminum chloride (AlCl 3 ) for eight weeks, and to study the therapeutic effects of vitamin E and C. AlCl 3 decreased the total red blood cell count (by 18%), hemoglobin (7%) and hematocrit (20%), and increased white blood cell count (67%), lymphocytes (29%), mean corpuscular volume (14%), mean corpuscular hemaglobin (6%) and platelets (33%). Administration of vitamin E with or without vitamin C failed to restore levels of red blood cell counts, hematocrit, mean corpuscular volume, mean corpuscular hemaglobin or platelets, but vitamin E on its own restored levels of white blood cells, hemaglobin and lymphocytes. AlCl 3 decreased serum glucose levels by 30%, and increased triglyceride (28%) and cholesterol (20%) levels; neither vitamin treatments restored the levels of these components. AlCl 3 increased levels of urea (12%), uric acid (77%) and creatinine (25%) compared to the controls, and vitamin E separately or together with vitamin C restored the levels of these nitrogen compounds. The activities of alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase were also increased by the AlCl 3 treatment; the first two but not aspartate aminotransferase were restored by vitamin E separately or together with vitamin C. We conclude that vitamin E separately or together with vitamin C suppressed cytogenetic injury and damage to some biochemical pathways of rat organs induced by AlCl 3

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

Kinin B1 Receptor Enhances the Oxidative Stress in a Rat Model of Insulin Resistance: Outcome in Hypertension, Allodynia and Metabolic Complications

BACKGROUND: Kinin B(1) receptor (B(1)R) is induced by the oxidative stress in models of diabetes mellitus. This study aims at determining whether B(1)R activation could perpetuate the oxidative stress which leads to diabetic complications. METHODS AND FINDINGS: Young Sprague-Dawley rats were fed with 10% D-Glucose or tap water (controls) for 8-12 weeks. A selective B(1)R antagonist (SSR240612) was administered acutely (3-30 mg/kg) or daily for a period of 7 days (10 mg/kg) and the impact was measured on systolic blood pressure, allodynia, protein and/or mRNA B(1)R expression, aortic superoxide anion (O(2)(*-)) production and expression of superoxide dismutase (MnSOD) and catalase. SSR240612 reduced dose-dependently (3-30 mg/kg) high blood pressure in 12-week glucose-fed rats, but had no effect in controls. Eight-week glucose-fed rats exhibited insulin resistance (HOMA index), hypertension, tactile and cold allodynia and significant increases of plasma levels of glucose and insulin. This was associated with higher aortic levels of O(2)(*-), NADPH oxidase activity, MnSOD and catalase expression. All these abnormalities including B(1)R overexpression (spinal cord, aorta, liver and gastrocnemius muscle) were normalized by the prolonged treatment with SSR240612. The production of O(2)(*-) in the aorta of glucose-fed rats was also measured in the presence and absence of inhibitors (10-100 microM) of NADPH oxidase (apocynin), xanthine oxidase (allopurinol) or nitric oxide synthase (L-NAME) with and without Sar[D-Phe(8)]des-Arg(9)-BK (20 microM; B(1)R agonist). Data show that the greater aortic O(2)(*-) production induced by the B(1)R agonist was blocked only by apocynin. CONCLUSIONS: Activation of kinin B(1)R increased O(2)(*-) through the activation of NADPH oxidase in the vasculature. Prolonged blockade of B(1)R restored cardiovascular, sensory and metabolic abnormalities by reducing oxidative stress and B(1)R gene expression in this model