MEDLINE Journals

    Tyrosine kinase inhibitor, genistein, reduces renal inflammation and injury in streptozotocin-induced diabetic mice.

    Authors
    Elmarakby AA, Ibrahim AS, Faulkner J, et al. 
    Source
    Vascul Pharmacol 2011 Nov-Dec; 55(5-6) :149-56.
    Abstract

    Tyrosine kinase inhibition is known to reduce diabetes-induced end-organ damage but the mechanisms remain elusive. We hypothesized that inhibition of tyrosine kinase reduces renal inflammation and injury in streptozotocin-induced diabetes. Male C57BL/6 mice were given daily injections of streptozotocin (45 mg/kg/day, i.p. for 5 days); control animals received the vehicle (citrate buffer). Thereafter, streptozotocin-treated mice were treated with genistein (10 mg/kg, i.p three times a week for 10 weeks, n=8-10/group) or the vehicle (5% DMSO). The streptozotocin-treated mice displayed significant elevation in blood glucose level and decrease in plasma insulin level compared to their vehicle-treated controls. Treatment with genistein reduced blood glucose level (~15%; p<0.05) without a significant effect on plasma insulin level; however, blood glucose remained significantly higher than the control group. The development of diabetes was associated with significant increases in total protein, albumin, nephrin and collagen excretions compared to their controls. In addition, the diabetic mice displayed increased urinary MCP-1 excretion in association with increased renal ICAM-1 expression and apoptotic cells. Furthermore, renal gp91 expression levels and urinary Thio-Barbituric Acid Reactive Substances (TBARs) excretion, indices of oxidative stress, were also elevated in diabetic mice. These changes were associated with increased renal phospho-tyrosine expression and renal phospho-ERK/ERK ratio. Importantly, treatment with genistein reduced all these parameters towards control values. Collectively, the results suggest that the reno-protective effect of genistein likely relates to reduced renal inflammation, oxidative stress and apoptosis in diabetic mice.

    Mesh
    Animals
    Anti-Inflammatory Agents, Non-Steroidal
    Antioxidants
    Apoptosis
    Biological Markers
    Cells, Cultured
    Diabetes Mellitus, Type 1
    Diabetic Nephropathies
    Genistein
    Humans
    Kidney
    MAP Kinase Signaling System
    Male
    Mesangial Cells
    Mice
    Mice, Inbred C57BL
    Oxidative Stress
    Phosphorylation
    Protein Kinase Inhibitors
    Protein Processing, Post-Translational
    Random Allocation
    Streptozocin
    Language

    eng

    Pub Type(s)
    Journal Article Research Support, Non-U.S. Gov't
    PubMed ID

    21807121

    Content Manager
    Related Content

    Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin-induced type 1 diabetes.

    Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats.

    Resveratrol prevents renal lipotoxicity and inhibits mesangial cell glucotoxicity in a manner dependent on the AMPK-SIRT1-PGC1α axis in db/db mice.

    Adenosine Kinase Inhibition Protects The Kidney Against Streptozotocin-Induced Diabetes Through Anti-inflammatory and Anti-oxidant Mechanisms.

    Protective effect of short-term genistein supplementation on the early stage in diabetes-induced renal damage.

    Prevention of early renal injury by mycophenolate mofetil and its mechanism in experimental diabetes.

    Induction of hemeoxygenase-1 reduces glomerular injury and apoptosis in diabetic spontaneously hypertensive rats.

    Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db/db mice.