الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
This study investigates the possible protective effects of levocetirizine and sulforaphane against fructose-induced insulin resistance, hepatic steatosis and vascular dysfunction, incomparison to pioglitazone, a standard insulin sensitizer. Male Sprague Dawley rats (150–200g) were divided into 5 groups. Four groups were fed on high fructose diets (HFrD) containing 60% w/w fructose, while the fifth control group was fed on standard laboratory food for 61 days. Both treatments offered protection against insulin resistance (indicated by AUCITT and HOMA-IR), glucose intolerance (indicated by AUCOGTT), hepatic oxidative stress, inflammation (indicated by C-reactive protein level) and tissue damage (indicated by lactate dehydrogenase activity). Liver steatosis scores and endothelial dysfunction were attenuated by both agents. HOMA-β was restored by Levocetirizine. These findings demonstrate for the first time that levocetirizine ameliorates insulin resistance, improves glucose tolerance and attenuates insulin resistance-linked hepatic steatosis and vascular damage. Sulforaphane (SFN), is known to exhibit beneficial effects in the vessel wall. Nevertheless, the vasoprotective role of SFN has not been examined in the setting of obesity characterized by hyperleptinemia and insulin resistance. Using the mouse model of western diet-induced obesity, the present study demonstrates for the first time that SFN (0.5 mg/kg/day, s.c.) for ~ 3 weeks significantly attenuates neointima formation in the injured femoral artery [↓neointima/media ratio by~60%]. This was associated with significant improvements in metabolic parameters, including ↓ weight gain by~52%, ↓ plasma leptin by ~ 42%, ↓ plasma insulin by ~ 63%, insulin resistance [↓HOMA-IR index by ~ 73%], glucose tolerance (↓ AUCGTT by ~ 24%), and plasma lipid profile. Under in vitro conditions, SFN significantly decreased leptin-induced VSMC proliferation by ~ 23% with associated diminutions in leptin-induced cyclin D1 expression and the phosphorylation of p70S6kinase and ribosomal S6 protein. The present findings reveal that, in addition to improving systemic metabolic parameters, SFN inhibits leptin-induced VSMC proliferative signaling that may contribute in part to the suppression of injury-induced neointima formation.