Chronological Appearance of Endocrine and Metabolic Dysfunctions Induced by an Unhealthy Diet in Rats.

Background and Objectives: The work was aimed to determine the chronological sequence of events triggered by a fructose-rich diet (FRD) (10% w/v in the drinking water) in normal rats. Material and Methods: Serum parameters, liver and islet markers of metabolism, inflammation and oxidative stress were determined weekly for 21 days. Results: At the end of the first week, rats fed with a FRD showed an early increase in circulating triglycerides, fat liver deposit, and enzymatic activity of liver glucokinase and glucose-6-phosphate dehydrogenase (G6P-DH). After two weeks of such a diet, liver glucose-6-phosphatase (G6Pase) activity and liver oxidative stress markers were significantly increased. Liver sterol regulatory element-binding protein 1c (SREBP1c) mRNA also increased in the second week while their target genes fatty acid synthase (FAS) and glycerol-3-phosphate dehydrogenase (GPAT) enhanced their expression at the third week. Liver and pancreatic inflammation markers also enhanced their gene expression in the last week of treatment. Whereas both control and FRD rats remained normoglycemic throughout the entire period of treatment, blood insulin levels were significantly higher in FRD animals at the third week, thereby evidencing an insulin-resistant state (higher HOMA-IR, HOMA-B and HIS indexes). Pancreatic islets isolated from rats fed with a FRD for 3 weeks also increased glucose-induced insulin secretion (8.3 and 16.7 mM). Conclusions: FRD induces asynchronous changes involving early hypertriglyceridemia together with intrahepatic lipid deposit and metabolic disturbances from week one, followed by enhanced liver oxidative stress, liver and pancreas inflammation, pancreatic ß-cell dysfunction, and peripheral insulin-resistance registered at the third week. Knowledge of time-course adaptation mechanisms involved in our rat model could be helpful in developing appropriate strategies to prevent the progression from prediabetes to Type 2 diabetes (T2D) triggered by unhealthy diets.

Antioxidant and cytotoxic properties of an aqueous extract from the Argentinean plant Hedeoma multiflorum.

CONTEXT: Hedeoma multiflorum Benth. (Lamiaceae) is widely used in Argentinean popular medicine for digestive and anti-spasmodic purposes. However, knowledge about its pharmacological properties has been poorly investigated. OBJECTIVE: The antioxidant and cytotoxic properties of an aqueous extract from the plant were investigated for the first time. MATERIAL AND METHODS: Scavenging of stable free radicals of 2,2-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS(+)) and 2,2-diphenyl-1-picryl hydrazyl (DPPH), reducing of ferric (III) iron of ferric reducing ability of plasma (FRAP) reagent, and inhibition of lipid peroxidation (LP) of human plasma and rat brain homogenates were assessed. Cytotoxicity was tested on human polymorphonuclear (PMN) cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cytotoxicity was assessed by flow cytometric techniques. RESULTS: Extract scavenged ABTS(+) and DPPH (1.78 and 0.78 µmol Trolox equivalent/mg dry extract, respectively) and reduced FRAP reagent (0.66 µmol ascorbic acid equivalent/mg dry extract). LP of human plasma and rat brain was also inhibited in a dose-dependent way (inhibitory concentration 50%=27.0 and 86.0 µg/mL, respectively). Extract is rich in polyphenol compounds (0.96 ± 0.08 µmol equivalent caffeic acid/mg dry matter). Treatment of PMN decreased significantly the cell ability to reduce the MTT salt and increased the hypodiploid nuclei from 4 to 18% quantified using propidium iodide (PI). In the annexin V-Fluorescein isothiocyanate (annexin V-FITC) assay, 26% of treated cells were annexin V-FITC positive and PI negative. Using the 3,3'-dihexyloxacarbocyanine iodide uptake method, the negative fraction of cells was calculated as 29%. DISCUSSION AND CONCLUSION: H. multiflorum extract was found to have a significant antioxidant and pro-apoptotic activities, and a great potential as a source of healthy products.