RESUMO
This study investigated the influence of betulinic acid on high-fructose diet-induced metabolic syndrome in rats. Oral administration of betulinic acid significantly reversed high-fructose diet-mediated increase in body mass index and blood glucose. Furthermore, betulinic acid restored high-fructose diet-mediated alterations in metabolic hormones (insulin, leptin and adiponectin). Betulinic acid-mediated upregulation of protein kinase B (Akt) and phosphoinositde-3 kinase (PI3K) anulled high-fructose diet mediated depletion. Also, elevated tumour necrosis factor-α, interleukin-6 and -8 were significantly lowered. Administration of betulinic acid restored high-fructose diet-mediated increase in the levels of lipid profile parameters and indices of atherosclerosis, cardiac and cardiovascular diseases. High-fructose diet-mediated decrease in activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase) and increase in oxidative stress biomarkers (reduced glutathione, lipid peroxidation products, protein oxidation and fragmented DNA) were significantly restored by the phenolic acids. Conclusively, betulinic acid improves insulin sensitivity, elevated blood glucose, inflammation and dyslipidaemia and oxidative stress in high-fructose diet-induced metabolic syndrome through the PI#Kand Akt pathways .
Assuntos
Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Síndrome Metabólica/tratamento farmacológico , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Triterpenos/farmacologia , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Catalase/genética , Catalase/metabolismo , Colesterol/sangue , Dieta/efeitos adversos , Frutose/efeitos adversos , Regulação da Expressão Gênica , Glutationa/genética , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Hiperglicemia/etiologia , Hiperglicemia/genética , Hiperglicemia/metabolismo , Insulina/sangue , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Malondialdeído/antagonistas & inibidores , Malondialdeído/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Triterpenos Pentacíclicos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Ácido BetulínicoRESUMO
1,3-dichloro-2-propanol is a food-borne contaminant reported to cause liver injury. In this study, we evaluated the protective influence of caffeic acid on 1,3-dichloro-2-propanol-induced hepatotoxicity in rats. Rats were randomized into five groups (A-E). Rats received distilled water or caffeic acid (10 or 20 mg/kg body weight) for 7 days. In addition, rats were challenged with 1,3-dichloro-2-propanol on day 7. Caffeic acid prevented 1,3-dichloro-2-propanol-mediated alterations in alkaline phosphatase, alanine and aspartate aminotransferases, albumin and total bilirubin in the serum of rats. Furthermore, caffeic acid lowered superoxide ion, hydrogen peroxide and cytochrome P2E1 while increasing the activities of superoxide dismutase, catalase and glutathione S-transferase in the liver of 1,3-dichloro-2-propanol-treated rats. Caffeic acid raised the levels of nuclear erythroid-related factor 2 (Nrf-2), protein kinase A and phosphoinositide 3-kinase. Caffeic acid pretreatment annulled 1,3-dichloro-2-propanol-mediated alterations in the oxidative stress biomarkers; caspase-3, glutathione, malondialdehyde, protein carbonyl and fragmented DNA, in the liver of rats. Contrastingly, caffeic acid lowered 1,3-dichloro-2-propanol-mediated increase in the levels of nuclear factor-kappa B (NF-κB), tumour necrosis factor-α, interleukin-1ß (IL-1ß) and IL-6. In addition, caffeic acid preserved the morphological features of 1,3-dichloro-2-propanol-treated rats. Results from this study revealed that caffeic acid protects against 1,3-dichloro-2-propanol-induced hepatotoxicity by enhancing the cytoprotective enzymes through Nrf-2 while lowering inflammation through NF-κB.
Assuntos
Ácidos Cafeicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , alfa-Cloridrina/análogos & derivados , Animais , Ácidos Cafeicos/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Regulação para Baixo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Ratos , alfa-Cloridrina/toxicidadeRESUMO
We evaluated the inactivation of DNA gyrase on the oxidative stress response and sensitivity of A. baumannii to lophirones B and C. The sensitivity of parental and the mutant strains of A. baumannii to lophirones B and C was determined using minimum inhibitory concentration (MIC) and time-kill sensitivity. Inactivation of sodB, katG, recA enhanced the sensitivity of A. baumannii to lophirones B and C. Furthermore, this inactivation increased the accumulation of superoxide anion radical and hydrogen peroxide in lophirones B and C-treated A. baumannii, which was reversed in the presence of thiourea. Inactivation of gyrA stalled lophirones B and C-mediated ROS accumulation in A. baumannii. In addition, lophirones B and C raised the Fe2+ contents of A. baumannii. Dipyridyl (Fe chelator) reversed the sensitivity of A. baumannii to lophirones B and C. Lophirones significantly lowered the NAD+/NADH ratio of A. baumannii. The results of this study revealed that the impact of DNA gyrase in lophirones B and C-mediated ROS accumulation, Fe2+ release and cell death.