title: Levocetirizine ameliorates high fructose diet-induced insulin resistance, vascular dysfunction and hepatic steatosis in rats.
abstract: 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.
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors: Noha M
authors: NM
authors: Shawky
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. Electronic address: georgeshehatou@gmail.com.
authors: George S G
authors: GS
authors: Shehatou
authors: Urology and Nephrology center, Faculty of Medicine, Masnsoura University, Mansoura, Egypt.
authors: Mona
authors: M
authors: Abdel Rahim
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors: Ghada M
authors: GM
authors: Suddek
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors: Nariman M
authors: NM
authors: Gameil
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D017332:Cetirizine / Q000494:pharmacology / Q000627:therapeutic use*; D004032:Diet; D004435:Eating / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005632:Fructose; D005951:Glucose Tolerance Test; D005978:Glutathione / Q000378:metabolism; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D039563:Histamine H1 Antagonists, Non-Sedating; D007328:Insulin; D008055:Lipids; D020011:Protective Agents; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D005632:Fructose; C472067:levocetirizine; D002097:C-Reactive Protein; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D005978:Glutathione; D017332:Cetirizine
keywords: Acetylcholine (PubChem CID: 187); Aortic rings; Carboxymethyl cellulose (PubChem CID: 24748); Fructose (PubChem CID: 5984); Insulin resistance; Levocetirizine; Lipid profile; Oxidative stress; Phenylephrine (PubChem CID: 6041)