ESTROGENS IMPROVE THE CARDIOVASCULAR ALTERATIONS IN FRUCTOSE-INDUCED INSULIN RESISTANT OVARIECTOMIZED RATS

Objective: The present study aimed to investigate the possible improving effects of 17-β estradiol (EST) and genistein (GEN) on the cardiovascular changes associated with fructose (21% in drinking water for 8 weeks)-induced insulin resistance.Methods: Sham-operated and ovariectomized mature female rats were included in this study. Insulin-resistant ovariectomized animals were sc treated with EST (100 µg/kg) or GEN (1 mg/kg) on the daily basis for 21 consecutive days.Results: Induction of insulin resistance in both sham-operated and ovariectomized rats decreased the vascular responsiveness of isolated aortic rings towards the vasoconstrictor norepinephrine and the vasodilator acetylcholine (Ach) with no changes towards the vasodilator sodium nitroprusside. Fructose-induced insulin resistance was also associated with an elevation in the blood pressure (BP) with decreased serum level of nitric oxide (NO). Treatment of insulin-resistant ovariectomized rats with either EST or GEN improved the vascular responsiveness of isolated aortic rings towards Ach and succeeded to reduce the elevated BP. Moreover, both EST and GEN decreased the insulin resistance/compensatory hyper insulinaemia. Treatment with EST increased serum NO level.Conclusion: EST and GEN have the ability to improve the endothelium-dependent relaxation in insulin-resistant ovariectomized rats and modulate the elevated BP.Â

Streptozotocin-induced vascular and biochemical changes in rats: Effects of rosiglitazone vs. metformin

The aim was to investigate rosiglitazone and metformin effects on some vascular and biochemical changes associated with streptozotocin (55 mg/kg; i.p.)-induced hyperglycaemia in rats. Isolated aortas were used to evaluate their reactivity towards norepinephrine, acetylcholine, and sodium nitroprusside. Blood samples were used to assess the biochemical changes of some parameters viz., plasma lipid peroxides and nitric oxide levels and erythrocytic glutathione peroxidase activity. Hyperglycaemic animals orally received rosiglitazone (0.5 mg/kg) or metformin (150 mg/kg) daily for 2 weeks and their effects were determined 24 h after the last dose. Our results revealed that streptozotocin-induced hyperglycaemia is associated with impaired vascular reactivity towards various agents, increased lipid peroxides level, decreased glutathione peroxidise activity, and decreased nitric oxide level. Both drugs further decreased norepinephrine-induced contraction and improved acetylcholine- and sodium nitroprusside-induced relaxations. Rosiglitazone restored the alterations in all tested biochemical parameters while metformin restored only glutathione peroxidise activity. In conclusion both drugs show beneficial effects against the vascular dysfunction associated with hyperglycaemia which might be related to their euglycaemic activity in addition to anti-oxidant property of rosiglitazone and a direct effect of metformin on vascular smooth muscle

Detailed radiographic evaluation of articular damage.

<p>Data are presented as mean ± SEM.</p><p>n = 10.</p><p>a: significantly different from CIA-group at <i>p</i><0.05.</p><p>b: significantly different from LEF-group at <i>p</i><0.05.</p><p>Detailed radiographic evaluation of articular damage.</p

Intra-articular MPO activity.

<p>Mice with CIA were treated with leflunomide (LEF), nimesulide (NIM), or leflunomide+nimesulide (LEF+NIM) and compared to untreated arthritic and normal mice. Articular MPO activity was measured 40 days after treatment as a marker of leucocytic infiltration.</p

Symptomatic assessment of arthritis.

<p>Mice with CIA were treated with leflunomide (LEF), nimesulide (NIM), or leflunomide+nimesulide (LEF+NIM) and compared to untreated arthritic and normal mice. Hyperalgesia (A) and joint stiffness (B) were recorded at pre-arthritic, mid-arthritic and late arthritic phases of arthritis and compared to base line readings. Data are presented as mean ± SD. * Significantly different from normal mice; ** significantly different from CIA-mice.</p

Histopathological assessment of articular damage.

<p>Mice with CIA were treated with leflunomide (LEF: Panel C), nimesulide (NIM: Panel D), or leflunomide+nimesulide (LEF+NIM: Panel E) for 40 days and the H&E stained joints were compared with untreated arthritic (CIA: Panel B) and normal mice (Panel A). Pathological findings were compared in terms of synovial hyperplasia (S), articular irregularity (A), narrowing of joint space (N), and lymphocytic infiltration (M).</p