Efeitos metabÃlicos in vivo de derivados Benzilideno-Tiazolidinadionas

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Thiazolidinediones are insulin-sensitizing agents that working by binding to PPAR-γ, which leads to alteration in the expression of key regulators of lipid homeostasis, glucoregulatory and insulin resistance gene. In this study, it was evaluated the effect of treatment with novel benzylidene thiazolidinediones (BTZDs) derivatives: 5-(4-chlorobenzylidene)- 3-(4-methyl-benzyl)-thiazolidine-2,4-dione (GQ2), 5-(4-methoxybenzylidene)- 3-(4-methyl-benzyl)-thiazolidine-2,4-dione (GQ5), 5-(2,4-dimethoxybenzylidene)- 3-(4-methyl-benzyl)-thiazolidine-2,4-dione (GQ6), 5-(4-dimethylaminobenzylidene)- 3-(4-methyl-benzyl)-thiazolidine-2,4-dione (GQ10) on insulin resistance associated with hiperinsulinemia, hyperglycemia and hyperlipidemia in high-fat diet induced mice. Firstly, mice were allocated into two dietary regimens either chow diet or high fat diet, for the period of 75 days. After, the mice were randomly divided into 7 groups (n=6). The normal group (NC) and the high-fat diet control group (HFD-C) received vehicle (carboxymethylcellulose) and the other groups of mice were treated with GQ2, GQ5, GQ6, GQ10 and Rosiglitazone (all 30mg/Kg/day), once daily, orally for 15 days. All the groups except the normal group were on high-fat diet throughout the period of treatment. Body weight, serum triglyceride and total cholesterol levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting serum glucose levels (FSG) and fasting serum insulin levels (FSI) of all groups were assayed. Insulin resistance index were calculated using homeostasis model assessment (HOMA-IR). None of the treatments caused any significant alteration on body weight. The elevated serum triglyceride, total cholesterol, FSG and FSI levels reduced significantly (P<0.01) by BTZDs and rosiglitazone treated groups in comparison with HFD-C group. GQ5 was 34% more potent than rosiglitazone in terms of decrease insulin levels (P<0.05). HOMA-IR indices of BTZDs and rosiglitazone treated groups were significantly (P<0.01) improved when compared to the HFD-C group. Moreover, only GQ2 and GQ5 were able to reduce the serum AST levels when compared with HFD-C group. This study suggests that these BTZDs derivatives not only reduces insulin resistance in high-fat fed mice, but also corrected associated hyperinsulinemia, hyperglycemia and hyperlipidemia. Additionally, none of them exerted any major adverse effect on the liver or body weight.

ASSUNTO(S)

tiazolidinadionas hiperlipidemia biologia e fisiologia dos microorganismos hiperlipidemia benzilideno-tiazolidinadionas thiazolidinediones dieta benzylidene-thiazolidinediones diet

Documentos Relacionados