Fructose induced metabolic syndrome in rats, a role for Glitazones, fibrates and statins

The metabolic syndrome is a constellation of symptoms and signs that include central obesity, insulin resistance, dysglycemia. dyslipidemia and hypertension. .The present work aimed to study the effect of a Peroxisome Proliferator Activated Receptor-alpha [PPAR-alpha] agonist [fenofibrate], two PPAR-gamma agonists [rosiglitazone and pioglitazone] and a statin [simvastatin] on glycemic control and lipid profile in fructose-induced metabolic syndrome in rats. The study also aimed to assess the benefits gained from the combination of these agents. The present study was carried out on one hundred and ten white male albino rats. Ten rats received normal laboratory chow. The remaining rats were fed a high fructose diet for induction of metabolic syndrome X. The current study showed that treatment of fructose induced metabolic syndrome [FMS] rats with fenofibrate, rosiglitazone or pioglitazone was associated with significant improvement in glycemic control Fenofibrate treatment was associated with significant decrease in body weight in comparison to rosiglitazone or pioglitazone-treated rats that showed a significant body weight gain. Fenofibrate and simvastatin treatment of FMS rats caused a significant decrease in serum triglycerides [TGs,], cholesterol as well as significant increase in serum high density lipoproteins [HDL]. Only simvastatin resulted in a significant decrease in serum low density lipoproteins [LDL]. The combination of fenofibrate with rosiglitazone or pioglitazone was associated with less body weight gain and a more marked improvement in glycemic control The addition of simvastatin to fenofibrate and rosiglitazone or pioglitazone was associated with a significant improvement in lipid profile when compared to the combination offenofibrate with rosiglitazone or pioglitazone. No further significant improvement in glycemic was control achieved by the addition of simvastatin to nfenofibrate and rosiglitazone or pioglitazone. Given the close relationship between PPAR activity and the metabolic syndrome, PPAR agonists are promising therapeutic agents for diseases including type 2 diabetes mellitus [DM2]. obesity, hypertension, hyperlipidemia and atherosclerosis. Combination drug therapy, which utilizes complementary mechanisms, can be advantageous in patients with significant combined or mixed dyslipidemias. The combination of glitazones and statins was associated with the utmost glycemic control and improvement in lipid profile

comparative study between gliclazide, glibenclamide and glipizide on plasma glucose, C-peptide, lipid profile and on some peroxidative changes in diabetic rats

This study was performed on 50 male adult albino rats [10 normal and 40 alloxan-induced diabetic rats] divided into five groups, each of ten rats. The study recommended the use of gliclazide in NIDDM due to its excellent glycemic control and prevention of the long- term vascular complications; it also restores the abnormalities in lipid peroxides, oxidative markers and antioxidant enzymes

comparative study on the effect of bisoprolol and other A-blockers on the counter-regulation of insulin-induced hypoglycemia in the rat

The effect of bisoprolol, a new selective B[1] adrenoceptor blocker, on the counter-regulation of insulin induced hypoglycaemia [IIH] was studied and compared to the effect of propranolol and atenolol. Results showed that the pretreatment of rats with either of the three B blockers, propranolol [30 mg/kg], atenolol [50 mg/kg] or bisoprolol [10 mg/kg] for seven consecutive days did not affect plasma glucose nadir at 30 and 60 minutes after insulin injection [1U/kg, S.C.]. However, the glucose recovery rate measured at 120 minutes, was significantly reduced by propranolol and bisoprolol but not atenolol. Similarly the rebound of free fatty acid [FFA] in response to insulin was significantly attenuated by propranolol and bisoprolol whereas atenolol only reduced it. The rise in plasma corticosterone level measured at 30 and 60 minutes from IIH was significantly lowered by propranolol and bisoprolol while no significant effect was observed with atenolol pretreatment. Insulin induced depletion in plasma c-AMP levels were significantly potentiated by the pretreatment of rats with the three B blockers studied. However, at 120 minutes all the three B blockers significantly prevented insulin induced depletion in plasma c-AMP. Results presented indicate that bisoprolol shows less selectivity than atenolol at least in respect to glucose metabolism

comparative study on the effect of bisoprolol and other beta-blockers on the counter-regulation of insulin-induced hypoglycaemia in the rat

The effect of bisoprolol, a new selective beta 1 adrenoreceptor blocker, on the counter-regulation of insulin-induced hypoglycemia [IIH] was studied and compared to the effect of propranolol and atenolol. Results showed that the pretreatment of rats with either of the three beta-blockers, propranolol [30 mg/kg], atenolol [50 mg/kg] or bisoprolol [10 mg/kg], for seven consecutive days did not affect plasma glucose nadir at 30 and 60 minutes after insulin injection [1 U/kg, s.c.]. However, the glucose recovery rate measured at 120 minutes, was significantly reduced by propranolol and bisoprolol, but not atenolol. Similarly the rebound of free fatty acid [FFA] in response to insulin was significantly attenuated by propranolol and bisoprolol, whereas atenolol only reduced it. The rise in plasma corticosterone level measured at 30 and 60 minutes from IIH was significantly lowered by propranolol and bisoprolol, while no significant effect was observed with atenolol pretreatment. Insulin-induced depletion in plasma c-AMP levels were significantly potentiated by the pretreatment of rats with the three beta-blockers studied. However, at 120 minutes all the three alpha-blockers significantly prevented insulin-induced depletion in plasma c-AMP. Results presented indicated that bisoprolol showed less selectivity than atenolol at least in respect to glucose metabolism

effect of verapamil and nitrendipine on noradrenaline induced contraction of the isolated rabbit acritic strip

The possibility of the involvement of the alpha-adrenoceptors in the mechanism of calcium channel blockers inducing vasodilatation was investigated. The effects of verapamil, nifedipine and phentolamine have been compared on the contractions of the rabbit aortic strips produced by different concentrations of noradrenaline [NA] [10-7 - 10-4 M]. Results showed that preincubation of the rabbit aortic strip with a low concentration of verapamil [10-6 M] caused a parallel rightward shift of NA dose response curve, with significant depression of the minimal response induced by NA. A highly marked rightward shift of the NA dose response curve, with significant depression of the minimal response induced by NA. A highly marked rightward shift of the NA dose response curve was noticed with a higher concentration of verapamil [10-5 M]. This was accompanied by a highly significant depression of the minimal [P <0.001] and maximal [P <0.005] responses of NA. Similarly, phentolamine [10-7 M] produced a parallel rightward shift of the NA dose response curve with a highly significant inhibition of the responses induced by lower concentrations of NA [P <0.001]. On the other hand, nifedipine [10-6, 10-5 M] shifted the NA dose response curve to the right in a nonparallel manner and depressed only the maximal responses induced by NA. These observations suggested an alpha-antagonistic property of verapamil on the rabbit aortic strip which was not demonstrated with the other calcium channel blocker, nifedipine

Changes in renal function induced by long term treatment with bisoprolol, compared to other beta-adrenocepter blockers

The effect of long term treatment with bisoprolol, a new cardioselective beta-adrenoceptor blocker on some kidney function tests in the rat was studied and compared to atenolol and propranolol. Results showed that the oral administration of bisoprolol [10 mg/kg] caused a highly significant increase in plasma creatinine by 83% and 88% when measured after 3 and 5 weeks of daily treatment, respectively [P <0.001]. Significant increase [P <0.001] in plasma urea reaching 46% and 53% difference from control values was found when measured after 3 and 5 weeks of daily treatment, respectively. On the other hand, no significant change in plasma creatinine and urea levels were observed after oral daily treatment of rats with atenolol [50 mg/kg] for 1, 3 and 5 weeks. Treatment of rats with propranolol [30 mg/kg] elevated plasma creatinine level insignificantly by 6%, 24% and 25% when measured after 1, 3 and 5 weeks, respectively [P >0.05]. This was accompanied by minimal changes in plasma urea. All three beta-blockers tested, had no significant effect on total plasma proteins. Results showed that beta-adrenoceptor blockers produce changes in the kidney function regardless of their cardioselectivity. The possible mechanisms of action by which bisoprolol induced such changes were discussed

comparative study of the effects of bisoprolol, atenolol and propranolol on plasma lipids and lipoprotein cholesterol in the rat

The effect of short and long term B-adrenergic blockade on plasma lipids and lipoproteins was studied. Results revealed a highly significant increase in plasma triglycerides of rats treated with either bisoprolol [10 mg/kg] or propranolol [30 mg/kg] over a period of 3 and 5 weeks. Atenolol [50 mg/kg], however, did not significantly alter plasma triglyceride levels of rats treated over a period of either 1, 3 or 5 weeks [P >0.05]. Total plasma cholesterol was significantly decreased after treatment of rats with bisoprolol over a period of 1, 3 or 5 weeks. A significant decrease in plasma cholesterol was evident after propranolol treatment when measured after 1 [P <0.001] and 3 [P <0.01] weeks. On the other hand, atenolol significantly decreased plasma cholesterol after 3 and 5 weeks [P <0.001]. The lipoprotein pattern of rats treated with the beta-blockers changed fairly markedly. Thus, atenolol significantly decreased low density lipoprotein [LDL]-cholesterol after 3, 5 weeks [P <0.001] with no significant change in high-density lipoprotein [HDL]-cholesterol. After one week of treatment, however, atenolol significantly increased LDL [P <0.001]. Propranolol, on the other hand, significantly decreased LDL after 3 [P <0.001] and 5 [P <0.01] weeks of daily treatment. However, a significant decrease in HDL was also found after 1 [P <0.001] and 3 [P <0.05] weeks of propranolol treatment. Bisoprolol significantly decreased LDL after 5 weeks of bisoprolol treatment, the highly significant [P <0.001] decrease in LDL was coupled by a significant [P <0.05] increase in the beneficial HDL-cholesterol. The data suggested that both propranolol and atenolol may induce significant, potentially atherogenic changes in lipid metabolism, whereas bisoprolol is relatively advantageous as an alternative in the management of hypertension, especially in subjects with an already atherogenic lipoprotein profile

hypoglycemic effect of chlorimipramine in normal anddiabetic rats

The present study was undertaken to determine the effect of chlorimipramine [CIM], a tricyclic antidepressant, on plasma glucose and insulin levels in normal and diabetic rats. Fasted male Wister rats were treated with four doses of CIM [5, 10, 20, 40 mg/kg]. This was either given as a single dose, one hour prior to blood sampling [acute] or daily for seven consecutive days [chronic]. Results showed that CIM caused a dose-dependent decrease in the plasma glucose level in both the acute and chronic treated normal rats. This hypoglycemic effect was associated with a significant rise in immuno-reactive insulin [IRI when given in lower doses [5 and 10 mg/kg]. In diabetic rats, CIM [0.5 and 5 mg/kg] significantly reduced plasma glucose level with increased level of insulin. However, CIM showed no effect on plasma glucose level of diabetic rats previously treated with soluble insulin [0.4 and 1 U/kg]. These findings may have clinical implications regarding the treatment of depressed diabetic patients

effect of verapamil on brain monoamines of rats pretreated with nialamide and reserpine

The present work investigated the acute effect of verapamil on the brain levels of 5-hydroxytryptamine [5HT], dopamine [DA] and noradrenaline [NA] in nialamide and reserpine pretreated rats. Results showed that treatment of rats with verapamil [5 mug/kg] one hour prior to sacrifice significantly increased brain 5HT and decreased DA brain level. However, brain NA level showed no significant difference compared to control values. Treatment of rats with nialamide, significantly increased brain 5HT, DA and NA levels. In nialamide pretreated rats, verapamil [5 mug/kg] revealed a highly significant increase was slightly higher than that produced by either verapamil or nialamide alone, it did not reach statistical significance. Moreover, pretreatment of rats with nialamide completely blocked the verapamil-induced decrease in brain DA level. On the other hand, the treatment of rats with reserpine, significantly depleted brain 5HT, DA and NA levels. The verapamil-induced increase in brain 5HT was blocked by the pretreatment of rats with reserpine. However, reserpine pretreatment revealed a synergistic effect with the calcium antagonist on brain DA level, where a highly significant depletion was evident. The possible mechanisms by which verapamil induced these changes in brain monoamines was discussed

Verapamil: a calcium channel blocker and its effect on brain monoamines in the rat

The present work is an attempt to investigate the effect of verapamil, a calcium channel blocker, on brain 5 hydroxytryptamine [5 HT], dopamine [DA] and noradrenaline [NA]. Results showed that the intraperitoneal [i.p.] injection of verapamil in doses of 1, 5, 25 and 50 mug/kg, one hour prior to sacrifice, significantly increased brain 5 HT level. A significant decrease in brain DA was detected with doses of 5, 25 and 50 mug/kg of verapamil, while 1 mug/kg caused no significant change in this parameter. Brain NA level, however, was not significantly changed with all the doses of verapamil previously mentioned when measured one hour from the injection of the drug. The mechanism of action of verapamil in the management of affective disorders and the possibility of the involvement of brain 5 HT and DA was discussed

in vitro comparative study of the effect of Verapamil and aminophylline on the histamine induced contraction of the guinea pig tracheal chain

We investigated the inhibitory effect of verapamil, a calcium channel blocker, against histamine induced contraction [HIC] on the isolated guinea pig tracheal smooth muscle and compared it with aminophylline. Results showed that verapamil [1.1 and 2.2 X 10[-4]M] significantly inhibited HIC when incubated with the tissue before histamine challenge. Aminophylline was less effective when incubated with the tissue in equimolecular concentrations. In higher concentrations however, aminophylline [3.6 X 10[-4]M] significantly prevented HIC. As regards to the reversal of HIC, aminophylline was found to be more potent than verapamil

Imipramine: a tricyclic antidepressant and its effect on plasma glucose, insulin and free fatty acids levels in the rabbit

A study on the effect of imipramine, a tricyclic antidepressant, on plasma glucose, immunoreactive insulin [IRI] and free fatty acids [FFA] levels is presented. The results show that the administration of imipramine causes a significant increase in the plasma glucose level of fasting rabbits. The increase was found to be dose dependent. The imipramine induced hyperglycaemia was associated with a significant decrease in the plasma immunoreactive insulin level. An elevation in the plasma FFA levels was evident at 10 and 30 minutes from the injection. However, at 60 minutes a rise in plasma FFA was shown with higher doses only [25 and 50 mg/kg. b.w.]. This study gives further evidence for the possible effect of antidepressants on the glucose metabolic pathways

effect of a newly synthesised sulfonylurea derivative 1- [P- [3,5 dimethyl-pyrazole -1] carbomoylbenzene sulfonyl] - 3-cyclohexylurea [cycle SCC] on plasma lipids, some electrolytes and liver function tests in the rabbit

The effects of the acute and prolonged administration of a newly synthesised sulfonylurea derivative, [Cycle SCC], on plasma free fatty acids [FFA], triglycerides and cholesterol levels were studied. Serum sodium and potassium levels, in addition to some liver function tests were also measured. Results revealed a significant decrease in plasma FFA, of both normal and alloxan diabetic rabbits, when measured after the administration of one single dose of the drug. Moreover, after the prolonged administration of Cycle SCC, plasma FFA, triglycerides and cholesterol levels were significantly decreased. A significant decrease in serum sodium and potassium levels of diabetic, but not of healthy, rabbits was evident. No significant change was observed in the studied liver function tests [viz, serum glutamic pyruvic transaminase [SGPT, serum glutamic oxalacetic transaminase [SGOT] and serum alkaline phosphatase], indicating the relative safety of Cycle SCC from hepatotoxic effects