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