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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
Gosford Hospital
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.
DOI: 10.1111/1753-0407.12341
ISSN: 1753-0407
Publicaton type: Journal Article
Keywords: Research
Drug Therapy
Appears in Collections:Health Service Research

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