الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Insulin resistance (IR) is linked to several health conditions such as glucose intolerance, T2DM, dyslipidemia and hepatic steatosis. IR also increases the risk of various cardiovascular diseases .Glucocorticoid (GC) drugs top many other drugs in terms of variety of applications and pharmacological experience in humans. Nevertheless, GCs are extremely associated with metabolic syndrome and its hallmark, IR. The current study aimed at finding novel and safe pharmacological interventions that could protect against GCs-induced metabolic and vascular dysregulations. The possible beneficial effects of the phenolic compound, protocatechuic acid (PCA) and the novel xanthine oxidase inhibitor, febuxostat (FEB) against DEX-induced insulin resistance in rats and the induced metabolic dysregulations and vascular abnormalities were assessed. In the present study, male Wistar rats were treated with PCA (50 and 100 mg/kg, orally) or FEB (5, 10 and 15 mg/kg, orally) for 14 days and for the last 7 days rats were injected with dexamethasone (DEX) (1 mg/kg, i.p.) to establish a rat model of insulin resistance. PCA or FEB effects were investigated on fasting blood glucose, insulin, oral glucose tolerance test (OGTT), liver biomarkers, lipid profile, oxidative stress biomarkers in hepatic, aorta and muscle tissues, hepatic and aortic histopathological examination and aortic vascular reactivity. Additionally, the hepatic mRNA expression of gluconeogenic enzymes and aortic nitric oxide synthase3 (eNOS) and NADPH oxidase4 (NOX4) were determined. Moreover, insulin-mediated AKT phosphorylation was assayed in soleus muscle. Pretreatment with PCA and FEB significantly alleviated DEX-induced insulin resistance as shown by decreasing AUCOGTT, fasting serum glucose and insulin levels and HOMA-IR. In addition, they improved lipid profile, decreased serum ALT and AST activities. Additionally, they improved oxidative biochemical parameters, attenuated the hepatic mRNA expression of G6Pase and PEPCK while enhanced aortic eNOS and decreased aortic NOX4 mRNA expression level. Pretreatment with PCA and FEB decreased hepatic steatosis score and hepatic triglycerides content. Moreover, both drugs ameliorated insulin-mediated AKT phosphorylation in soleus muscle. The findings reported herein reveal that PCA and FEB exhibited promising protective potential and may be taken as supplements with GCs to limit their metabolic and vascular side effects through their hypoglycemic, insulin-sensitizing and antioxidant effects.