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|Title:||Dose-related antihyperglycemic and hypolipidemic effects of two novel thiazolidin-4-ones in a rodent model of metabolic syndrome||Authors:||Mathew, Geetha ;Karot, S.S.;Surenahalli, V.G.;Kishore, A.;Mudgal, J.;Nandakumar, K.;Chirayil, M.T.||Affliation:||Central Coast Local Health District
|Issue Date:||Sep-2016||Source:||8(5):629-39||Journal title:||Journal of Diabetes||Department:||Pharmacy||Abstract:||BACKGROUND: The replacement of the thiazolidinedione moiety with a thiazolidinone may yield antidiabetic compounds with similar pleiotropic effects. Hence, the aim of the present study was to explore the dose-related antihyperglycemic and hypolipidemic effects of two synthesized novel thiazolidin-4-one derivatives, one with a nicotinamide and the other with a p-chlorophenoxyacetamide substitution at the N3 position of the thiazolidinone ring (NAT1 and PAT1, respectively), in a rodent model of metabolic syndrome (MetS). METHODS: Metabolic syndrome was induced in Wistar rats by neonatal administration of monosodium glutamate (i.p.) on 4 consecutive days followed by high-sucrose diet feeding for 6 months. The effects of NAT1 (33 and 66 mg/kg) and molar equivalent doses of PAT1 (40 and 80 mg/kg) on relevant biochemical parameters were evaluated. Because MetS is a state of chronic low-grade inflammation, we also evaluated the effects of these compounds on proinflammatory markers, namely interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, reactive oxygen species (ROS), and nitric oxide (NO). RESULTS: Both NAT1 and PAT1 attenuated hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, and glucose intolerance. PAT1 exhibited superior antihyperglycemic and antihypoalphalipoproteinemic effects than NAT1. However, NAT1 had a better triglyceride-lowering effect. At the lower dose tested, both compounds significantly reduced elevated malondialdehyde levels. In addition, PAT1 (80 mg/kg) restored hepatic superoxide dismutase enzyme levels. There was a tendency for NAT1 and PAT1 to inhibit elevated hepatic IL-6 and TNF-alpha levels, but the differences did not reach statistical significance. In addition, PAT1 exhibited in vitro anti-inflammatory activity by reducing proinflammatory ROS and NO levels in RAW264.7 macrophages. CONCLUSIONS: The novel thiazolidin-4-ones NAT1 and PAT1 could be potential pleiotropic drug candidates targeting MetS.||URI:||https://elibrary.cclhd.health.nsw.gov.au/cclhdjspui/handle/1/1778||DOI:||10.1111/1753-0407.12341||Pubmed:||https://pubmed.ncbi.nlm.nih.gov/26345135/||ISSN:||1753-0407||Publicaton type:||Journal Article||Keywords:||Research
|Appears in Collections:||Health Service Research|
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