الفهرس 
Effect of Dapagliflozin, a Sodium-Glucose Transporter 2 Inhibitor, on Diabetic Neuropathy in Streptozotocin-induced Diabetes Mellitus in Rats
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Abstract
Diabetic neuropathy is a chronic condition that affects a significant number of
individuals with diabetes. Streptozotocin (STZ) injection intraperitoneally to rodents
produces pancreatic islet β-cell destruction causing hyperglycemia, which affects the
brain leading to memory and cognition impairment. Dapagliflozin may be able to
reverse beta-cell injury and alleviate this impairment. This effect may be via
neuroprotective effect or possible involvement of the antioxidant, and anti-apoptotic
properties. Forty rats were divided into four groups as follows: The normal control
group, the STZ-induced diabetes group, STZ-induced diabetic rats followed by
treatment with oral dapagliflozin group and normal rats treated with oral
dapagliflozin. Behavioral tests (Object location memory task and Morris water
maze) were performed. Serum biomarkers (blood glucose and insulin) were
measured and then the homeostatic model assessment for insulin resistance (HOMA-
IR) was calculated. In the hippocampus the following were determined; calmodulin,
ca-calmodulin kinase IV (CaMKIV), protein kinase A (PKA) and cAMP-responsive
element-binding protein to determine the transcription factor CREB and its signaling
pathway also Wnt signaling pathway and related parameters (WnT, B-catenin,
lymphoid enhancer-binding factor LEF, glycogen synthase kinase 3β). Moreover,
nuclear receptor-related protein-1, acetylcholine and its hydrolyzing enzyme
acetylcholine esterase, oxidative stress parameter malondialdehyde (MDA) and
apoptotic parameter caspase-3 were determined. STZ was able to cause destruction
to pancreatic β-cells which was reflected on glucose levels causing diabetes.
Diabetic neuropathy was clear in the rats performing the behavioral tests. Memory
and cognition parameters in the hippocampus were negatively affected. Oxidative
stress and apoptotic parameter were elevated while the electrical activity was
declined. Dapagliflozin was able to reverse the previously mentioned parameters and
behavior. Thus, to say dapagliflozin significantly showed neuroprotective action
along with antioxidant, and anti-apoptotic propertie