International Journal of Scientific and Research Publications, Volume 5, Issue 7, July 2015 1 ISSN 2250-3153 www.ijsrp.org Comparative effects of pioglitazone, α-lipoic acid, taurine and chromium picolinate and their combinations on hyperglycemic, lipid profile and oxidative stress parameters in fructose-induced insulin resistant rats Mohammed H. Moawad͙ ͙ , Hala F. Zaki, Ezz-El-Din S. El-Denshary Pharmacology & Toxicology Department, Faculty of Pharmacy, Cairo University, Kasr EL-Eini Street, P.O. Box 11562, Cairo, Egypt. Abstract- The potential of pioglitazone and certain micronutrients, namely, α-lipoic acid, taurine and chromium or their combinations to improve glycemic status and insulin resistance (IR), and their role in treating oxidative stress insults and dyslipidemia were studied. Seven groups of rats (n=8) were fed on fructose enriched diet (FED) for 18 weeks. One group served as FED-control, groups were daily treated with pioglitazone (7mg/kg), α-lipoic acid (600 mg/kg), taurine (600mg/kg), chromium (500mg/kg), and combination of pioglitazone with each of such micronutrients during the last 6 weeks of treatment. Another group was fed on normal laboratory chew (normal control group). At the end of the experiment, blood samples were taken by retro-orbital technique for estimation of markers related to IR. Induction of IR was associated with increased body weight gain (23.5%) coupled with elevated fasting blood glucose (134%), glycated hemoglobin (64%), triglycerides (6%), total cholesterol (29%), low density lipoprotein (62%). The level of high density lipoprotein was reduced (26%). Fructose-induced IR was accompanied by reduction of superoxide dismutase (85%) and glutathione (74%), whereas malondialdehyde was elevated (145%). Body weight gain was enhanced after treatment with pioglitazone, taurine and their combinations. Fasting blood glucose was lowered after treatment with pioglitazone, α-lipoic acid or taurine. It was normalized after co-administration of pioglitazone and chromium. Glycated hemoglobin was reduced by pioglitazone, taurine or chromium alone or in combination. Lipid profile and oxidative stress parameters were improved after pioglitazone administration, alone or along with each of the tested micronutrients. In conclusion, this study proves the benefits of co- administration of α-lipoic acid, taurine or chromium with pioglitazone in FED-induced IR models in rats. Index Terms- FED-fed rats, insulin resistance, oxidative stress, pioglitazone. I. INTRODUCTION etabolic syndrome (MS) is a constellation of risk factors for cardiovascular diseases and type II diabetes mellitus, characterized by obesity, dyslipidemia, IR and hyperglycemia (Hall et al., 2006). Changes of dietary habits including increased intake of simple sugar , mainly fructose commonly used in food industry and as a sweetener of soft drinks (Isomaa et al., 2001), contribute to the growing worldwide prevalence of MS. Oxidative stress has been reported to play an important role in type II diabetes mellitus (Siddiqui et al., 2005; Shukla et al., 2007). In animal models, excessive fructose intake is associated with IR, impaired glucose tolerance, hyperinsulinemia and hyperlipidemia (Elliot et al., 2002). Enhancement of insulin action might be an effective approach in alleviating MS. Insulin sensitizers increase peripheral tissue sensitivity to insulin without stimulating its release (Vekramadithyan et al., 2000). Thiazolidinediones, including pioglitazone are used for the treatment of IR and management of type II diabetes mellitus (Bailey, 1999; Dey et al., 2002). Pioglitazone is used for improvement of insulin sensitivity in muscles and adipose tissue (Georios et al., 2013). Micronutrients are effective in treating IR syndrome complications. Alpha lipoic acid is reported to be a necessary co- factor in mitochondrial energy metabolism. It also possesses an antidiabetic action (Liu et al., 2002; Suh et al., 2004). Taurine was reported to improve insulin sensitivity in fructose-fed rats (Nandhini et al., 2005), an action that was attributed to combating the destructive effects of free radicals on the pancreas. Chromium picolinate is an essential trace nutrient which is used as a nutritional supplement (Sawyer, 1994) with a central role in glucose metabolism. Chromium improves glucose tolerance by decreasing hepatic extraction in pigs (Guan et al., 2000). Its deficiency may lead to diabetes mellitus (Wada et al., 1983; Striffler et al., 1998). Chromium was reported to improve insulin sensitivity and modulate lipid metabolism in peripheral tissues (Anderson, 2008). Therefore, there is a need to search for a better alternative therapy for IR syndrome that is more effective and less toxic. The present work was therefore, carried out to investigate the possible beneficial effects of α-lipoic acid, taurine or chromium in fructose-induced insulin resistant syndrome alone or in combination with pioglitazone. II. MATERIALS AND METHODS Animals Adult male albino rats weighing about 180 gm/each were purchased from National Research Centre, Cairo, Egypt and left M