This study investigates the possible protective effects of
levocetirizine against
fructose-induced
insulin resistance, hepatic steatosis and vascular dysfunction, in comparison to
pioglitazone, a standard
insulin sensitizer. Male Sprague Dawley rats (150-200 g) were divided into 4 groups. Three groups were fed on high
fructose diets (HFD) containing 60% w/w
fructose, while the fourth control group was fed on standard laboratory food for 8 weeks. AUCOGTT, AUCITT, fasting
glucose, HOMA-IR, hepatic
glutathione (GSH) and
malondialdehyde (MDA) levels, serum total
cholesterol, LDL-C,
C-reactive protein (CRP) level and
lactate dehydrogenase (LDH) activity and
liver steatosis scores were significantly higher in HFD group compared to control group. Moreover,
body weight gain, food intake, feeding efficiency, HOMA-β, Emax and pEC50 of
acetylcholine-induced relaxations of aortic rings and hepatic
superoxide dismutase (SOD) activity were significantly lower in HFD group than in control group. Treatment with
levocetirizine caused significant decreases in AUCOGTT, AUCITT, HOMA-IR, hepatic GSH and MDA levels and serum CRP level and LDH activity and significant increases in hepatic SOD activity and HOMA-β when compared with the HFD group. Although
levocetirizine failed to alter TC and
LDL-C levels, it produced a significant increase in HDL-C level relative to control group.
Levocetirizine was also able to improve
acetylcholine-induced relaxations of aortic rings, indicating a protective effect against
insulin resistance-induced endothelial damage comparable to that offered by
pioglitazone. Moreover,
levocetirizine substantially attenuated
insulin resistance-associated liver macrovesicular steatosis. These findings demonstrate that
levocetirizine ameliorates
insulin resistance, improves
glucose tolerance and attenuates
insulin resistance-linked hepatic steatosis and vascular damage.