PPAR-gamma agonists: antioxidant and metabolic effects in fructose induced insulin resistant rats

The aim of the present study was to investigate oxidative stress in fructose induced model of insulin resistance in albino rats via measuring plasma superoxide dismutase enzyme [SOD enzyme]. Additionally, the present work compared the effects of two different insulin sensitizers, pioglitazone and rosiglitazone, on plasma glucose, plasma insulin, SOD enzyme, lipid profile, blood pressure and vascular reactivity in fructose induced model of insulin resistance in albino rats. The results revealed 20.38%* reduction of the superoxide dismutase enzyme in insulin resistant rats compared with the control. However, after giving PPAR-y agonists, pioglitazone and Rosiglitazone for 4 weeks, there was significant rise in SOD enzyme by 44.6 l%* in the former group compared to the latter, where there was significant rise by only 32.21%*. These PPAR-y agonists, also showed significant improvement in glycemic control, insulin resistance index, systolic blood pressure and specially lipid profile. The results of the present work indicate that these two agents have a promising place in the treatment of insulin resistance syndrome in humans not only due to their metabolic effects, but also due to their antioxidant action. In vitro experiments also revealed that pretreatment with pioglitazone and rosiglitazone were associated with blunting in aortic ring contractile response towards phenylephrine and enhanced endothelial dependent relaxation response to acetylcholine, compared to insulin resistant untreated group. Both drugs produced significant increase of effective concentration 50 [EC50] of phenylephrine by 60.7%* and 32.4%* respectively. Similarly, both drugs produced significant increase acetylcholine induced relaxation by 549%* and 40.8%* respectively when compared to insulin resistant group. However, pioglitazone proved to be more potent. These results are in accordance with the lowering of elevated systolic blood pressure in vivo experiments produced by both drugs

Leukotriene antagonist and dexamethazone: effects on airway functional and pathological changes after chlorine inhalation in guinea pigs

In an animal model of guinea pigs, search for any adverse effects was made, by studying functional and pathological changes in pulmonary airways that may arise from inhalation of increasing concentration of chlorine gas as in swimming pools and how to ameliorate these effects by administration of leukotriene antagonist [Montelukast] or corticosteroids [Dexamethazone] separately or in combination. The different parameters assessed in the present study included specific airway resistance [sRaw], tidal volume of guinea pigs subjected to chlorine inhalation, air way reactivity to acetyl choline [PC100] and total cell count and differential count in bronchoalveolar lavage [BAL] 48 hrs and 21 days after exposure to chlorine inhalation. Guinea pigs were divided into five groups, one group served as control. The other four groups were subjected to chlorine inhalation, one group of them not receiving any medication, while the other three groups received medication starting from half hour after chlorine exposure and for 21 days, either with montelukast receiving daily intraperitoneal injection of a dose 10 mg/Kg or receiving corticosteroid [dexamethazone] daily intraperitoneal injection of a dose 20 mg/Kg, while the last group received the two medications combined together. On analysis of the results, there were highly significant changes and worsening of all parameters in the group subjected to chlorine inhalation without any medication, compared to control, either 48 hours or 21 days after chlorine inhalation [p<0.001]. The only exception is cell count in bronchoalveolar lavage [BAL] which showed insignificant changes [p>0.05] either in total cell or differential count 21 days after chlorine inhalation. The present study also demonstrated significant improvement [p<0.001] after administration of leukotriene antagonist [montelukast] starting half hour after chlorine inhalation and for 21 days. Also, there was significant improvement after treatment with corticosteroids [dexamethazone] [p<0.001]. The highest improvement was recorded in the group receiving both medications montelukast and dexamethazone combined together. However the results of the present study demonstrated that montelukast, although it produced marked improvement, yet it was the least effective in this respect, followed by dexamethazone and the best improvement was noticed when the two medications were combined together

Significance of different imidazoline receptors in pancreas and CNS and their role in control of plasma glucose, plasma insulin, lipid profile and blood pressure in fructose induced insulin resistant rats

The present study was carried out to elucidate the main difference between the various types of imidazoline receptors in the CNS and pancreas. The second generation selective imidazoline receptor agonist rilmenidine was used as a tool in the present study to demonstrate the difference of action on imidazoline receptors in these sites. An animal model of fructose induced insulin resistance in rats, similar to the metabolic syndrome X in human was adopted in the present work. The present study proved the ability of imidazoline receptor agonist rilmenidine to block ATP sensitive K+ channels, involved in the release of insulin in the pancreas via stimulation of 13 receptors. It also proved the ability of rilmenidine to normalize metabolic changes on lipid profile and to correct dyslipidemia that occurred in this condition. Moreover, rilmenidine lowered raised systolic blood pressure in fructose induced insulin resistant rats; due to additional effect on imidazoline I1 receptors in kidney, besides the main action on RVLM [rostral ventrolateral medulla] the final common pathway for sympathetic vasomotor outflow. The results revealed highly significant reduction of plasma glucose by 40.02%*, plasma insulin by 25.45%* and lipid profile [cholesterol by 25.42%*, triglycerides by 24.86%* and LDL by 44.92%*], while HDL was increased by 57.92%* [p<0.001] in insulin resistant group treated with rilmenidine. It also produced significant drop in the systolic blood pressure [p<0.001]. The difference in this action amounted to 30.91%* drop in BP with rilmenidine, compared with non-treated fructose induced insulin resistant group and insignificant change from normal control group [p>0.05]. In conclusion, the present work proved the presence of imidazoline binding site I3 in pancreas, previously called non I1 or I2. It also proved the effect of imidazoline receptor agonist rilmenidine to normalize the metabolic and haemodynamic effects that occur in fructose induced insulin resistant rats, supporting its use in diabetic hypertensive patients and in the metabolic syndrome X

Different measures that antagonize the overproduction of superoxide in blood vessels in hypercholesterolemic rats

The present study was an attempt to find out best measures which may be used to antagonize the superoxide overproduction in experimentally induced hypercholesterolemia in rats through increasing superoxide dismutase enzyme [S.O.D] and preserving nitric oxide. In this regard, three measures were tried in the hypercholesterolemic rats that were divided into three groups. The first group was treated with L-arginine [the natural precursor of nitric oxide], the second group was treated with ACE inhibitor captopril [capoten] and the third group was subjected to exercise. In all groups, the following parameters were investigated after sacrifice of the animals. Blood samples were taken, centrifuged, and serum was collected for estimation of lipid profile [Cholesterol, Triglycerides, LDL and HDL] and superoxide dismutase enzyme. The results revealed that, in addition to improvement of lipid profile in all the three hypercholesterolemic groups treated with L-arginine, ACE inhibitor [captopril] or subjected to exercise, there was significant elevation of superoxide dismutase enzyme from [185.5 +/- 18.73] to [240.25 +/- 21.55] U/ml [+29.51%] in the group treated with capoten, and significant elevation in the group treated with L-arginine to [245.75 +/- 21.11] U/ml [+32.47%] and significant elevation in the group subjected to exercise to [270.25 +/- 4.47] U/ml [+45.68%] indicating that, exercise proved to be the best measure to do so, followed by L-arginine, and lastly came the ACE inhibitor capoten. However, all the three mentioned measures proved to have beneficial effects in hypercholesterotemic rats

Effects of aerobic exercies and hypocaloric diet on serum leptin in healthy obese women

The aim of the present study was to determine the effect of aerobic exercise for three months and hypocaloric diet on serum leptin in healthy obese women together with the correlation between body mass index [BMI], waist/hip ratio [WHR], fasting blood sugar, glycosylated hemoglobin [HbA1C], plasma total cholesterol, triglycerides and blood pressure readings. Twenty adult obese female patients were selected based on the measured WHR and BMI. Pre- and post-aerobic exercise intervention for three months revealed that serum leptin levels correlated positively with the percentage of body fat and body mass index. After an aerobic exercise for three months and hypocaloric diet, serum leptin levels decreased significantly from mean values of 16.54 +/- 2.6 to 12.44 +/- 2.33 ng/ml with a reduction percentage of -24.7%. BMI also declined significantly from 39.48 +/- 5.004 before exercise to 37.08 +/- 4.52 three months after aerobic exercise and hypocaloric diet. The percentage of reduction was -6.1%. In addition, WHR declined significantly from mean values of 1.023 +/- 0.0531 to 0.973 +/- 0.0538 with a reduction percentage of -4.88%. Also, the study revealed an improvement of other parameters compared with pre- and post-aerobic exercise for three months with hypocaloric diet