@Article{ecn.2012.0309,
AUTHOR = {Nehal M. Elsherbiny, Khaled H. Abd El Galil, Mahmoud M. Gabr, Mohammed M. Al-Gayyar, Laila A. Eissa, Mamdouh M. El-Shishtawy},
TITLE = {Reno-protective effect of NECA in diabetic nephropathy: implication of IL-18 and ICAM-1},
JOURNAL = {European Cytokine Network},
VOLUME = {23},
YEAR = {2012},
NUMBER = {3},
PAGES = {78--86},
URL = {http://www.techscience.com/ECN/v23n3/65697},
ISSN = {1952-4005},
ABSTRACT = {Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease. Although,
adenosine acts as a local modulator with a cytoprotective function, extracellular adenosine usually disappears
quickly due to a rapid uptake into adjacent cells. Therefore, we investigated the effect of 5'
-(N-ethylcarboxamido)-
adenosine (NECA), a stable, nonselective adenosine receptor agonist, on diabetes-induced increases in inflammatory
cytokines and adhesion molecules. The enhancement of adenosine receptor action by NECA was examined in the
renal tissues of rats with streptozotocin-induced diabetes. Daily i.p. injections of NECA at 0.3 mg/kg/day were
given to rats, over a two-week period, six weeks after the induction of diabetes. Morphological changes were
assessed in kidney sections. Oxidative stress was examined by measuring tissue malondialdehyde. Gene expression
of interleukin (IL)-18, tumor necrosis factor (TNF)-α and intercellular adhesion molecule (ICAM)-1 was measured
by real-time PCR. Activation of cellular, proapoptotic pathways was demonstrated by measuring the activation
of c-Jun NH2-terminal kinases (JNK)-mitogen-activated-protein kinase (MAPK). We found that diabetes-induced
malondialdehyde formation activated the production of IL-18, TNF-α and ICAM-1, which, in turn, activated proapoptotic
pathways in diabetic rats. Treatment with NECA protected diabetic rats by exerting hypoglycemic and
antioxidant effects as well as reducing gene expression of proinflammatory cytokines. These effects were associated
with deactivation of JNK-MAPK. In addition, diabetic rats treated with NECA showed mild glomerular effects and
vacuolation of tubular epithelium. We can conclude that activation of adenosine receptors is a potential therapeutic
target in DN. NECA acts via multiple mechanisms including: reducing diabetes-induced oxidative stress, inhibiting
gene expression of IL-18, TNF-α and ICAM-1, and blocking activation of the JNK-MAPK pathway.},
DOI = {10.1684/ecn.2012.0309}
}