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Abstract The present investigation was done on three sets, the first set aimed to evaluate the possible role of sildenafil in fructose-induced metabolic syndrome. The 2nd set aimed to evaluate the possible protective effect of selective and non selective COX-inhibitors with or without metformin in the same model, meanwhile, the 3rd set aimed to explore the effect of combination of sildenafil with celecoxib and ω-nitro L-arginine on MS. In the present study, male albino rats (150-200 gm each) were received 20% fructose (10% to drinking water (weight/volume) and 10% to chow diet (weight/weight) for 6 weeks for induction of MS. In all sets, at the end of the experiment period, the animals weighed and sacrificed, thereafter, blood samples were collected; sera were separated and stored at -80°c until assessment of various parameters. In the 1st set, different doses of sildenafil selected for this investigation included (5, 10 and 40 mg/kg/day, p.o.), to clarify the possible role of PDE inhibition in prevention of fructose-induced metabolic syndrome. Rats were randomly divided into 5 main groups, control non-diseased, MS positive control, sildenafil (5 mg/kg/day)-treated, sildenafil (10 mg/kg/day)-treated and sildenafil (40 mg/kg/day)-treated groups. Results of the 1st set clearly demonstrated that: • Fructose feeding increased both liver weight and visceral fat weight indices, as compared to control non-diseased group. It also increased TG and cholesterol and reduced HDL, meanwhile, it increased fasting blood glucose, fasting insulin, HOMA-IR, uric acid, CRP, TNF-α, ALT, urea, serum creatinine, serum MDA, liver MDA and renal MDA. At the same time, it reduced creatinine clearance, serum catalase, serum reduced glutathione, and total nitrites in serum, liver and kidney. There was also a significant reduction in liver and kidney eNOS and a significant increase in liver and kidney iNOS and caspase-3, as compared to control group.. There was a fatty liver with bridging necrosis and necro-inflammatory foci and renal cloudy swelling with casts in histopathological examination. |