This work was designed to investigate the effects of
levocetirizine, a
histamine H1 receptor antagonist, on diabetes-induced nephropathy and vascular disorder, in comparison to an
angiotensin II receptor antagonist,
losartan. Diabetes was induced in male Sprague Dawley rats by a single
intraperitoneal injection of
streptozotocin (50mg/kg). Diabetic rats were divided into three groups; diabetic, diabetic-
levocetirizine (0.5mg/kg/day) and diabetic-
losartan (25mg/kg/day). Treatments were started two weeks following diabetes induction and continued for additional eight weeks. At the end of the experiment, urine was collected and serum was separated for biochemical measurements. Tissue homogenates of kidney and aorta were prepared for measuring oxidative stress,
nitric oxide (NO), transforming growth factor-β1 (TGF-β1) and
tumor necrosis factor-α (TNF-α). Moreover, histological analyses were conducted and aortic vascular reactivity was investigated.
Levocetirizine improved renal function in diabetic rats (evidenced by mitigation of diabetes-induced changes in kidney to
body weight ratio,
serum albumin, urinary
proteins and
creatinine clearance). Moreover,
levocetirizine attenuated the elevated renal levels of TNF-α and TGF-β1, ameliorated renal oxidative stress and restored NO bioavailability in diabetic kidney. These effects were comparable to or surpassed those produced by
losartan. Moreover,
levocetirizine, similar to
losartan, reduced the enhanced responsiveness of diabetic aorta to
phenylephrine. Histological evaluation of renal and aortic tissues further confirmed the beneficial effects of
levocetirizine on
diabetic nephropathy and revealed a greater attenuation of diabetes-induced vascular
hypertrophy by
levocetirizine than by
losartan. In conclusion,
levocetirizine may offer comparable renoprotective effect to, and possibly superior vasculoprotective effects than,
losartan in
streptozotocin-diabetic rats.