Diabetes mellitus is an endocrine disorder that is associated with several
microvascular and macrovascular complications in addition to complications within
the central nervous system (CNS). Diabetic encephalopathy secondary to chronic
hyperglycemia is mediated through oxidative stress, increased advanced glycation end
products (AGEs), and impairment in cerebral insulin signaling.
The Aim of the work was to investigate whether inhibition of aldose reductase and
arginase enzyme can protect against vascular and behavior complications.
Diabetes was induced in male wistar rats by a single intraperitoneal injection of
streptozotocin (STZ, 50 mg/kg). Eight weeks later, diabetic rats were orally treated
with ferulic acid (20 mg/kg), cinnamaldehyde (20 mg/kg), norvalline (50 mg/kg),
ornithine (200 mg/kg) and citrulline (50 mg/kg) every day for 8 weeks. Body weight,
blood glucose, serum AGEs level, blood pressure and behavioral change in memory
and cognition were investigated at the end of the study.
Streptozotocin caused a state of hyperglycemia associated with both vascular
and behavioral complications as evidenced by the elevation in blood pressure and
reduction in the Y-maze score and elevation in the transfer latency in the elevated plus
maze. Blockade of aldose reductase and arginase enzyme ameliorated some of these
complications without exerting any hypoglycemic effect.
These results suggest the possible effectiveness of aldose reductase and arginase
inhibitors in the management of diabetic vascular and behavioral complications
together with conventional antidiabetic therapy.