Antihyperlipidemic Activity of Glycoconjugated Phthalimides in Mice Submitted to a Model of Dyslipidemia and Insulin Resistance.
Mice
Animals
Insulin Resistance
Hypolipidemic Agents
/ pharmacology
Cholesterol, LDL
Uric Acid
Carboxymethylcellulose Sodium
Triglycerides
Dyslipidemias
/ drug therapy
Phthalimides
/ pharmacology
Lipoproteins, VLDL
Diabetes Mellitus, Type 2
Obesity
/ drug therapy
Simvastatin
Hormones
Transaminases
Insulins
cyclic imides
insulin resistance
obesity
phthalimides
Journal
Chemistry & biodiversity
ISSN: 1612-1880
Titre abrégé: Chem Biodivers
Pays: Switzerland
ID NLM: 101197449
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
06
02
2022
accepted:
08
09
2022
pubmed:
13
9
2022
medline:
22
10
2022
entrez:
12
9
2022
Statut:
ppublish
Résumé
Alterations in lipid and lipoprotein metabolism are factors that trigger several negative metabolic complications. Hyperlipidemia is the starting point for the development of comorbidities of the cardiovascular system, such as atherosclerosis. The search for compounds that reduce high levels of total cholesterol and triglycerides has been widely reported in several publications in the literature. Phthalimide derivatives have been extensively researched with various biological actions. In this study we evaluated the antihyperlipidemic ability of three phthalimide derivatives (FGT-2, FGT-3 and FGT-4) on a model of obesity and insulin resistance in mice. The animals were submitted to a hyperlipid diet for 60 days. On the thirtieth day they were treated with phthalimides (20 mg/kg). The positive control group was treated with Simvastatin (20 mg/kg) and the negative control received only the carboxymethylcellulose vehicle. Biochemical and histological analyzes of all groups were analyzed. The animals treated with phthalimidic derivatives had a reduction in total cholesterol, low density and very low density lipoproteins (LDL-c and VLDL-c), triglycerides and fasting glycemia when compared to the negative control group. The treated animals also showed good results when analyzing the atherogenic indexes Castelli i and II and the ratio Triglycerides/HDL-c. In the oral glucose tolerance test and in the insulin tolerance test, animals treated with phthalimides were more sensitive to the action of the hormone regulating carbohydrate uptake. In the evaluation of the transaminases (AST/ALT), the animals of the group treated with phthalimides presented a lower elevation than the other groups of the experiment, the same observed with the uric acid evaluation. Histological analyzes were performed on liver, kidney, heart and pancreas samples. The groups treated with the compounds FGT-2 and FGT3 presented discrete alterations in the liver and kidney. FGT-4 did not present histological alterations for both tissues and the three phthalimide derivatives did not cause alterations in the other organs. These results suggest that the phthalimides tested can act as antihyperlipidemic agents and have a pleiotropic action, by acting also reducing glycemia in insulin resistance model mimicking diabetes mellitus type 2. These compounds may appear as a new approach in the treatment of obesity and complications, which are multifaceted.
Identifiants
pubmed: 36094678
doi: 10.1002/cbdv.202200119
doi:
Substances chimiques
Hypolipidemic Agents
0
phthalimide
1J6PQ7YI80
Cholesterol, LDL
0
Uric Acid
268B43MJ25
Carboxymethylcellulose Sodium
K679OBS311
Triglycerides
0
Phthalimides
0
Lipoproteins, VLDL
0
Simvastatin
AGG2FN16EV
Hormones
0
Transaminases
EC 2.6.1.-
Insulins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202200119Subventions
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) by Fellowship (VLML)
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : 001
Organisme : Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE)
ID : PBPG-1492-2.08/14
Organisme : Researcher Fixation Scholarship
ID : BFP-0080-2.08/20
Informations de copyright
© 2022 Wiley-VHCA AG, Zurich, Switzerland.
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