Resveratrol is a polyphenolic compound which is found in many nutrients including grapes, peanuts, raspberries, and apples. Anti-proliferative, anti-angiogenic and apoptotic effects of resveratrol have been shown on various cancer cells. Doxorubicin is considered as one of the most effective anticancer agents and reveals its antitumor activity by induction of apoptosis and inhibition of angiogenesis. Our study reports for the first time the potent ability of resveratrol in combination with doxorubicin to inhibit angiogenesis in vitro and in vivo. The cytotoxic effect of resveratrol (1.56-100 μM), doxorubicin (0.01-0.92 µM) and their combination were analyzed in the human umbilical vein endothelial cells (HUVECs) by ATP assay. In vitro angiogenesis was evaluated using tube formation assay in HUVECs. In vivo anti-angiogenic activity was assessed in a chick chorioallantoic membrane (CAM) model using fertilized chicken eggs. All test groups were compared to thalidomide as a positive control, three concentrations of resveratrol (10-5-2.5 µg/pellet) and a 2 µg/pellet concentration of doxorubicin was examined. All data were evaluated statistically. Resveratrol and doxorubicin alone displayed inhibitory effects on angiogenesis and cell viability at higher doses. However, the combination of resveratrol and doxorubicin exhibited a significant dose-dependent inhibition of CAM angiogenesis in vivo as well as proliferation and tube formation in HUVECs compared to the positive control (±)-thalidomide. Our results suggest that resveratrol in combination with doxorubicin is a novel strategy in the prevention and treatment of angiogenesis.
Fatty acids are very important biological substances due to their metabolic, structural and signal- ing functions. Omega-3 has different beneficial, harmful and neutral effects on adipokines. Adi- pokines have autocrine, paracrine and endocrine effects on metabolism. In the study 54 German Fawn x Hair crossbred goats were synchronized using intravaginal sponges. During the first pe- riod (mating-75 days), all animals were fed a diet supplemented with protected fat and during the second period of pregnancy (76 days-kidding), one of the groups was fed a diet supplemented with fish oil and other was fed a diet supplemented with protected fat. Serum leptin, ghrelin, adi- ponektin and omentin levels were measured by ELISA system. Distributed fed (roughage and concentrate) were sampled and dry matter, crude protein, fat, and ash were determined by AOAC (1988) analysis methods. The Acid Detergent Fiber (ADF) and Neutral Detergent Fiber (NDF) analysis were conducted using heat stable α-amylase and sodium sulphite. Fat source (fish oil or protected fat) affected feed consumption and the highest feed consumption was found in the group fed with protected oil first half of the pregnancy and with fish oil in the second half of the pregnancy and in the fish oil group during the pregnancy. It was determined that the use of fish oil during pregnancy did not affect ghrelin, leptin and omentin concentrations in serum. Adipokine levels of fish oil fed animals during any period of pregnancy were found to be high and it was also found that serum adiponectin levels in goats fed with diet containing fish oil in the first half of pregnancy and protected fat in the second half were statistically significantly high in adipokines.