The melatonin receptor antagonist luzindole induces the activation of cellular stress responses and decreases viability of rat pancreatic stellate cells.

In this study, we have examined the effects of luzindole, a melatonin receptor-antagonist, on cultured pancreatic stellate cells. Intracellular free-Ca2+ concentration, production of reactive oxygen species (ROS), activation of mitogen-activated protein kinases (MAPK), endoplasmic reticulum stress and cell viability were analyzed. Stimulation of cells with the luzindole (1, 5, 10 and 50 µm) evoked a slow and progressive increase in intracellular free Ca2+ ([Ca2+ ]i ) towards a plateau. The effect of the compound on Ca2+ mobilization depended on the concentration used. Incubation of cells with the sarcoendoplasmic reticulum Ca2+ -ATPase inhibitor thapsigargin (1 µm), in the absence of Ca2+ in the extracellular medium, induced a transient increase in [Ca2+ ]i . In the presence of thapsigargin, the addition of luzindole to the cells failed to induce further mobilization of Ca2+ . Luzindole induced a concentration-dependent increase in ROS generation, both in the cytosol and in the mitochondria. This effect was smaller in the absence of extracellular Ca2+ . In the presence of luzindole the phosphorylation of p44/42 and p38 MAPKs was increased, whereas no changes in the phosphorylation of JNK could be noted. Moreover, the detection of the endoplasmic reticulum stress-sensor BiP was increased in the presence of luzindole. Finally, viability was decreased in cells treated with luzindole. Because cellular membrane receptors for melatonin have not been detected in pancreatic stellate cells, we conclude that luzindole could exert direct effects that are not mediated through its action on melatonin membrane receptors.

Lycopene and Melatonin: Antioxidant Compounds in Cosmetic Formulations.

BACKGROUND: The use of antioxidants has become a common practice in the development of antiaging cosmetics. OBJECTIVE: The aim of this study was to evaluate the clinical efficacy of cosmetic formulations containing lycopene and melatonin antioxidants. METHOD: Thirty-six healthy women from 32 to 65 years were enrolled in this study. The study was carried out for 10 weeks, 2 preconditioning weeks with a control cream without antioxidants, and 8-week test with creams containing antioxidants in study. A multifunctional skin physiology monitor (Courage & Khazaka electronic GmbH®, Germany) was used to measure skin sebum content, hydration, elasticity, erythema index, and melanin index in 4 different regions of the face. RESULTS: There were significant differences between them.

Anti-inflammatory effects of melatonin in a rat model of caerulein-induced acute pancreatitis.

The purpose of our study was to evaluate the protective effect of melatonin in a rat model of caerulein-induced acute pancreatitis. For the induction of experimental acute pancreatitis, four subcutaneous injections of caerulein (20 mgkg­1 body weight) were given to Wistar rats at 2-h intervals. Melatonin was injected intraperitoneally (25 mg kg­1 body weight) 30 min before each caerulein injection. After 12 h, rats were sacrificed by decapitation. Blood and pancreas samples were collected and processed for serological and histopathological studies,respectively. Lipase, a-amylase, corticosterone, total antioxidant power and cytokines interleukin (IL)-1b, IL-4 and tumour necrosis factor(TNF)-a were determined using commercial kits. ANOVA and Tukey tests (P<0.05) were performed for the statistical analysis of the results.Results showed that the administration of melatonin reduced histological damage induced by caerulein treatment as well as the hyperamylasemia and hyperlipidemia. Corticosterone and antioxidant total power were also reverted to basal activities. Furthermore, melatonin pre-treatment reduced pro-inflammatory cytokines IL-1b and TNF-a and increased the serum levels of anti-inflammatory cytokine IL-4. In conclusion,the findings suggest that the protective effect of melatonin in caerulein-induced acute pancreatitis is mediated by the anti-inflammatory ability of this indolamine. Thus, melatonin may have a protective effect against acute pancreatitis.

A lycopene-enriched virgin olive oil enhances antioxidant status in humans.

BACKGROUND: Lycopene, a bioactive red pigment, represents the most potent in vitro antioxidant among carotenoids. Virgin olive oil contains trace amounts of a wide variety of phytochemicals, which have proven to exert beneficial effects on oxidative stress. Since the ingestion of lycopene together with oil reportedly increases its bioavailability, we evaluated urinary antioxidant capacity after the consumption of a lycopene-enriched virgin olive oil (7 mg lycopene day(-1)) compared with the antioxidant effect produced after the ingestion of a virgin olive oil and a sunflower oil during 5 days, in young (25-30 years of age), middle-aged (35-55 years of age) and elderly (65-85 years of age) subjects. RESULTS: The results showed that the consumption of virgin olive oil increased urinary antioxidant capacity in middle-aged and elderly volunteers, whereas the administration of a lycopene-enriched virgin olive oil produced higher antioxidant effects in all of the three age groups assayed. CONCLUSION: The incorporation of the lycopene-enriched virgin olive oil into the diet may enhance the health-promoting effects of the virgin olive oil, contributing as a functional tool against several disorders where oxidative stress plays an important role.

Melatonin enhances hydrogen peroxide-induced apoptosis in human promyelocytic leukaemia HL-60 cells.

Melatonin is an indoleamine secreted by the pineal gland that shows multiple tasks. This ubiquitously acting free radical scavenger has recently been shown to stimulate the production of reactive oxygen species (ROS) in tumour cells, making them undergo apoptosis, whilst it prevents apoptosis in healthy cells. The mechanisms by which melatonin exerts these dual actions are, however, not yet clearly understood. Thus, the aim of this study was to further investigate how melatonin can enhance oxidative stress-induced apoptosis in a leukaemia cell line. The results show that melatonin increased the apoptotic effects of H(2)O(2) in human myeloid HL-60 cells as assessed by cellular viability, mitochondrial permeability transition induction, mitochondrial membrane depolarization, ROS generation, caspases 3, 8 and 9 activity, phosphatidylserine externalization, and DNA fragmentation techniques. When healthy leucocytes were exposed to H(2)O(2), melatonin increased the viability of the cells. Taken together, the findings indicate that melatonin is a potential physiological tool capable of protecting healthy cells from chemotherapy-induced ROS production as well as inducing tumour cell death. Because cancer cells manifest increased oxidative stress as a result of their elevated metabolism, the use of melatonin may be useful in impairing their ROS buffering capacity.

Effect of exogenous melatonin on viability, ingestion capacity, and free-radical scavenging in heterophils from young and old ringdoves (Streptopelia risoria).

The decrease of melatonin production with aging contributes to the decline in immune function as organisms age. Treatment with the exogenously administered indoleamine restores the reduced immunological functions. Therefore, we investigated the effect of melatonin on viability, phagocyte ingestion capacity, and free radical generation levels of heterophils from young and old ringdove (Streptopelia risoria) aged 3-4 and 11-13 years, respectively. Animals received a single oral dose of melatonin 1 h before lights off for three consecutive days. Experiments were performed at the acrophases and nadirs of melatonin. Melatonin treatment significantly increased serum melatonin levels at the acrophases, but not at the nadirs of the two age groups. In both young and old animals there was increased heterophil viability at acrophases with respect to nadirs, and also increased cell resistance to oxidative stress in the old animals after the melatonin treatment. At acrophases, the index, percentage and efficiency of phagocytosis all increased significantly, and superoxide anion levels decreased significantly with respect to the nadir values of vehicle and melatonin-treated animals, the effect being greater in young than in old ringdoves. At the nadirs, no change was observed in any parameter analyzed. In both young and old animals, phagocytosis and melatonin were positively correlated, while superoxide anion levels and melatonin were negatively correlated. In conclusion, exogenous melatonin enhanced heterophil viability in old animals as well as increasing phagocytosis and free-radical scavenging in both age groups during the nocturnal period, accompanied by an increase in the levels of the indoleamine.