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

Ahmed A. Elmarakby, Ahmed S. Ibrahim, Jessica Faulkner, Mahmood S. Mozaffari, Gregory I. Liou, Rafik Abdelsayed

Research output: Contribution to journalArticle

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalVascular Pharmacology
Volume55
Issue number5-6
DOIs
StatePublished - Nov 1 2011

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Keywords

  • Albuminuria
  • Diabetes
  • Gp91phox
  • ICAM-1
  • Nephrinuria
  • P-tyrosine

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

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