Saime Batirel

Resveratrol: French Paradox Revisited

Resveratrol is a polyphenol that plays a potentially important role in many disorders and has been studied in different diseases. The research on this chemical started through the “French paradox,” which describes improved cardiovascular outcomes despite a high-fat diet in French people. Since then, resveratrol has been broadly studied and shown to have antioxidant, anti-inflammatory, anti-proliferative, and anti-angiogenic effects, with those on oxidative stress possibly being most important and underlying some of the others, but many signaling pathways are among the molecular targets of resveratrol. In concert they may be beneficial in many disorders, particularly in diseases where oxidative stress plays an important role. The main focus of this review will be the pathways affected by resveratrol. Based on these mechanistic considerations, the involvement of resveratrol especially in cardiovascular diseases, cancer, neurodegenerative diseases, and possibly in longevity will be is addressed.

Alpha linolenic acid and oleic acid additively down-regulate malignant potential and positively cross-regulate AMPK/S6 axis in OE19 and OE33 esophageal cancer cells

OBJECTIVE Both oleic acid (OA) and alpha-linolenic acid (ALA) have been proposed to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that OA and/or ALA suppresses to the development of esophageal cancer has not been studied. Also, no previous studies have evaluated how OA and/or ALA regulates malignant potential (cell proliferation, migration, colony formation and adhesion) and intracellular signaling pathways, and whether their effects might be synergistic and/or additive in esophageal cancer cells has not yet been elucidated. MATERIALS/METHODS We conducted in vitro studies and evaluated whether OA and ALA alone or in combination may regulate malignant potential in OE19 and OE33 esophageal cancer cell lines. RESULTS Both OA and ALA significantly down-regulated cell proliferation, adhesion and/or migration. OA and/or ALA did not change the number of colonies but decrease colony sizes when compared to control. Also, we observed that OA and/or ALA positively cross-regulates the expression levels of AMPK/S6 axis. Moreover, OA and ALA up-regulated tumor suppressor genes (p53, p21, and p27) and these effects are abolished by AMPK siRNA administration. Importantly, we observed that these effects are additively regulated by OA and ALA in combination when compared to control in OE19 and OE33 esophageal cancer cell lines. CONCLUSIONS Our novel mechanistic studies provide evidence for an important role for OA and ALA in esophageal cancer, and suggest that OA and/or ALA might be useful agents in the management or chemoprevention of esophageal cancer.

The effect of Irisin on antioxidant system in liver.

Nonalcoholic fatty liver disease (NAFLD) is a global health problem and lead to subacute liver failure, cirrhosis and/or hepatocellular carcinoma. An increased generation of reactive oxygen species (ROS) and antioxidant depletion is found in the liver of obese patients with NAFLD. Irisin is a recently identified exercise-induced myokine. It increases total energy consumption, reduces body weight, and insulin resistance. It was shown that irisin levels were significantly lower in patients with NAFLD. The aim of the present study was to investigate the effect of irisin on prooxidant-antioxidant balance in liver. In the first phase; AML12 liver cells were divided into 4 groups: control, hydrogen peroxide (H2O2)-treated, 10nM irisin-treated and 50nM irisin-treated groups. ROS accumulation in these groups was analyzed by FACS. In the second phase; to see if there is any protective role of irisin on ROS production in the liver, AML12 liver cells were divided into 4 groups: control, H2O2 -treated, H2O2+10nM irisin-treated and H2O2+50nM-irisin treated groups. After measuring ROS accumulation again in these groups, the levels of enzymes related with prooxidant-antioxidant balance via oxidative stress in liver were measured by western blotting. In H2O2 treatment groups, ROS production was increased in AML12 liver cells, on the other hand in irisin treatment groups ROS production was slightly changed. Irisin might be a potential target for metabolic diseases like NAFLD.

Cellular Protection and Therapeutic Potential of Tocotrienols

Tocotrienols, components belonging to vitamin E members, are used as potent therapeutics in the treatment of several diseases. Recent studies suggested tocotrienol to have better activity in many situations compared to tocopherols. Tocotrienols have been shown to lower the atherogenic apolipoprotein B and lipoprotein plasma levels. Additionally, tocotrienols with their anti-tumor effect together with anti-angiogenic and anti-thrombotic effects may serve as effective agents in cancer therapy. Besides these effects, some properties such as water insolubility and low stability limit the usage of tocotrienols in the clinic. However recent studies tried to increase the bioavailability with esterification and combination use. These efforts for the clinical usage of tocotrienols which may help them to take a wide place in the clinic and additional studies are needed to identify their therapeutical mechanisms.

Effects of short-term streptozotocin-induced diabetes and vitamin C on platelet non-enzymatic glycation.

Diabetes mellitus is one of the most prevalent metabolic syndromes worldwide. Glycation, a chemical modification of proteins with reducing sugars, indicates a possible explanation for the association between hyperglycemia and the wide variety of tissue pathologies. Non-enzymatic glycation (NEG) of platelet proteins is one of the key mechanisms in the pathogenesis of diabetic complications and may be significant in diabetic atherothrombosis. The aim of this study was to investigate the effects of streptozotocin (STZ)-induced short-term experimental diabetes on the glycation of platelets and to find out if vitamin C affected this glycation. A total of 40 male Wistar albino rats, 200–250 g, were randomly divided into 4 groups (2 diabetic and 2 control groups). The diabetic groups were made diabetic by intraperitoneal injection of STZ (65 mg/kg, citrate buffer pH 4.5). By daily intraperitoneal injection, 80 mg/kg vitamin C (Roche, Turkey) was administered until the end of the experiment. Blood glucose levels of the diabetic groups were significantly higher than those at day 0 and also higher than those of the non-diabetic control groups. The changes in total protein, NEG and vitamin C levels were not statistically significant. Although the differences among the groups were not statistically significant, vitamin C administration increased NEG levels in the diabetic group. The results of this study demonstrate that 8 days of STZ-induced short-term diabetes did not cause a significant increase in NEG of platelets. However, the effect of vitamin C on platelet NEG needs to be further investigated.

Supplementation of docosahexaenoic acid (DHA) / Eicosapentaenoic acid (EPA) in a ratio of 1/1.3 during the last trimester of pregnancy results in EPA accumulation in cord blood

Omega-3 fatty acids (n-3 FA), specifically DHA, are associated with fetal growth and development. We aimed to determine the levels of DHA and EPA in cord serum after n-3 FA supplementation during the last trimester of pregnancy. Among 55 women, 23 were administered daily one capsule of n-3 FA supplement, involving DHA/EPA in a ratio of 1/1.3. Twenty nine women were enrolled as control group. Blood samples were collected at 22-24 weeks of gestation and at delivery. Fatty acids were analyzed with the method of GC-MS. Cord DHA level increased and EPA level decreased in both groups between the days of 22-24 and delivery. However, decrease in cord EPA level was significant in control group (p < 0.001) but not in supplement group (p > 0.05). Supplementation of DHA/EPA in a ratio of 1/1.3 during the last trimester of pregnancy caused higher cord EPA level compared to control group indicating an accumulation in umbilical cord.