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Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: Effects on hepatic PPAR-γ receptors.

Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: Effects on hepatic PPAR-γ receptors.
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Elaidy SM, Hussain MA, El-Kherbetawy MK,


Elaidy SM, Hussain MA, El-Kherbetawy MK, (click to view)

Elaidy SM, Hussain MA, El-Kherbetawy MK,

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Canadian journal of physiology and pharmacology 2017 12 15() doi 10.1139/cjpp-2017-0533
Abstract

Targeting Peroxisome Proliferator-Activated Receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for the diabetes mellitus (DM)-type 2. The PPAR-γ modulators display improvements in the insulin sensitizing and adverse effects of the traditional thiazolidinediones (TZDs). Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand, with agonistic post-transcriptional effects. Currently, NTZ-antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin (HFD/STZ) rat model of type-2 diabetes was explored. Diabetic adult male Wistar rats were treated orally by either PIO (2.7 mg/kg/day) or NTZ (200 mg/kg/day) for 14, 21, and 28 days. Body weights, fasting blood glucose, insulin resistance, lipid profiles, and liver and kidney functions of rats were assayed. The hepatic glucose metabolism, and PPAR-γ protein expressional levels, as well as the hepatic, pancreatic, muscular, and renal histopathology, were evaluated. Significant time-dependent euglycemic, and insulin sensitizing effects, with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase (G-6-P) and glucose-6-phosphate dehydrogenase (G-6-PD) enzymes, and PPAR-γ proteins expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM-type-2. Further systematic NTZ/PPAR-γ receptor subtypes molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.

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