RESUMEN
Overfeeding of a hypercaloric diet leads to obesity, diabetes, chronic inflammation, and fatty liver disease. Although limiting fat or carbohydrate intake is the cornerstone for obesity management, whether lowering fat or reducing carbohydrate intake is more effective for health management remains controversial. This study used murine models to determine how dietary fat and carbohydrates may influence metabolic disease manifestation. Age-matched C57BL/6J mice were fed 2 hypercaloric diets with similar caloric content, one with very high fat and low carbohydrate content (VHF) and the other with moderately high fat levels with high sucrose content (HFHS) for 12 weeks. Both groups gained more weight and displayed hypercholesterolemia, hyperglycemia, hyperinsulinemia, and liver steatosis compared to mice fed a normal low-fat (LF) diet. Interestingly, the VHF-fed mice showed a more robust adipose tissue inflammation compared to HFHS-fed mice, whereas HFHS-fed mice showed liver fibrosis and inflammation that was not observed in VHF-fed mice. Taken together, these results indicate macronutrient-specific tissue inflammation with excess dietary fat provoking adipose tissue inflammation, whereas moderately high dietary fat with extra sucrose is necessary and sufficient for hepatosteatosis advancement to steatohepatitis. Hence, liver and adipose tissues respond to dietary fat and sucrose in opposite manners, yet both macronutrients are contributing factors to metabolic diseases.
Asunto(s)
Tejido Adiposo/efectos de los fármacos , Carbohidratos de la Dieta/farmacología , Grasas de la Dieta/efectos adversos , Ingestión de Alimentos/efectos de los fármacos , Hígado/efectos de los fármacos , Sacarosa/efectos adversos , Tejido Adiposo/patología , Animales , Inflamación/inducido químicamente , Inflamación/patología , Resistencia a la Insulina , Lipoproteínas/sangre , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Phthalimido-alkyl-1H-1,2,3-triazole derivatives 3a-d and 4a-d were efficiently synthesized using 1,3-dipolar cycloaddition reaction. Anti-inflammatory activity and toxicity studies were performed. The results demonstrated that all the tested compounds reduced carrageenan-induced paw edema and indicated no lethality for toxicity against Artemia salina and acute toxicity in vivo (LD50 up to 1 g kg -1). Furthermore, the structure of phthalimide linked to phenyl group proved to be more active than the compounds containing benzothiazole moiety. Structural modifications such as removal of the phthalimide group and subsequent acetylation, to exemplify a non-cyclic amide, demonstrate that the phthalimide and triazole moieties are important for design of potent candidates with anti-inflammatory drug proprieties. Docking into the cyclooxygenase-2 (COX-2) confirms the importance of the phthalimide and triazole groups in the anti-inflammatory activity. The histopathological studies showed that the compounds 3a-d and 4a-d did not cause serious pathological lesions liver or kidneys.
Asunto(s)
Antiinflamatorios no Esteroideos/síntesis química , Diseño de Fármacos , Ftalimidas/síntesis química , Triazoles/síntesis química , Animales , Antiinflamatorios no Esteroideos/farmacología , Edema/tratamiento farmacológico , Ftalimidas/farmacología , Relación Estructura-Actividad , Triazoles/farmacologíaRESUMEN
This study reports the molluscicidal activity of usnic acid isolated from Cladonia substellata Vanio (lichen) on embryos at various stages of development and in adult mollusks of Biomphalaria glabrata. The toxicity of usnic acid was also evaluated through Artemia salina larvae mortality. Usnic acid was extracted with diethyl ether, isolated, purified, and its structure confirmed by analyzing the spectra of proton nuclear magnetic resonance. LC90 for 24â¯h of exposure were 1.62, 4.45, 5.36, and 4.49⯵gâ¯mL-1 for blastula, gastrula, trocophore, and veliger embryonic stages, respectively, and 3.45⯵gâ¯mL-1 for adult snails; LC50 of usnic acid against A. salina was 2.46⯵gâ¯mL-1. LC90 assessed 7â¯days after exposure was 2.56⯵gâ¯mL-1 for adult mollusks. In conclusion, these findings demonstrate that under laboratory conditions usnic acid has teratogenic and molluscicide potential to control the aquatic snail B. glabrata and may prove to be a promising candidate in the search for new molluscicide agents, but further detailed studies on its molluscicidal effect and possible environmental effects are needed.