Reactive oxygen species (ROS) are essential for sperm physiological functions such as capacitation, hyperactivation, and acrosome reaction, on the one hand, and for stimulating the apoptotic processes involved in the regulation of spermatogenesis, on the other hand. However, the imbalance between production and removal of ROS leads to oxidative stress, which is referred to as one of the main factors involved in male infertility. The pineal hormone melatonin, given its low toxicity and well-known antioxidant capacity, could be an excellent candidate to improve sperm quality. For this reason, the objective of the present work was to analyze whether long-term supplementation with melatonin to infertile men affects human sperm quality and the quality of the embryos retrieved from their couples. Our findings showed that the daily supplementation of 6 mg melatonin, as early as after 45 days of treatment, produced an increase in melatonin endogenous levels, indirectly measured as urinary 6-sulfatoxymelatonin (aMT6-s), an enhancement of both urinary and seminal total antioxidant capacity, and a consequent reduction in oxidative damage caused in sperm DNA. Moreover, couples whose men were given melatonin showed a statistically significant increase in the percentage of grade A (embryo with blastomeres of equal size; no cytoplasmic fragmentation), B (embryo with blastomeres of equal size; minor cytoplasmic fragmentation), and C (embryo with blastomeres of distinctly unequal size; significant cytoplasmic fragmentation) embryos at the expense of grade D (embryo with blastomeres of equal or unequal size; severe or complete fragmentation.) embryos which were clearly reduced. In summary, melatonin supplementation improves human sperm quality, which is essential to achieve successful natural and/or assisted reproduction outcome.

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.

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.

The decrease of melatonin with age contributes to immunosenescence. Its restoration via tryptophan may have immuno-enhancing effects. Therefore, we determined the effect of tryptophan administration on circulating serotonin, melatonin, cell viability, phagocytic function and levels of free radical generation of blood heterophils from old ringdoves ( Streptopelia risoria ), aged 11-13 years. The animals received a single oral capsule of  -tryptophan 1 hr after the onset of the light period. The tryptophan treatment significantly increased serum melatonin and serotonin levels, cell viability, phagocytosis index and phagocytosis percentage. Superoxide anion levels decreased significantly with respect to vehicle values, with the nocturnal reduction being greater than that which occurred during the light period. This suggests that orally administered tryptophan at the beginning of the day enhanced heterophil viability, phagocytic response and detoxification of superoxide anion radicals deriving from this immune function, as a result of the immunoregulatory action of melatonin and serotonin.Melatonin ( N -acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, is produced and secreted into the blood in a circadian manner with maximal production occurring during the dark phase of the light-dark cycle. The synthesis and secretion of melatonin act by providing information to the organism about its overall temporal organization and synchronize diurnal and seasonal changes in the immune system [1].There is a gradual decline in the melatonin rhythm as animals age: the amplitude and mean levels of melatonin undergo a significant reduction, known as the 'melatonin deficiency state ' [2]. In addition, stress seems to lower the circulating levels of the indoleamine [3]. As a result, the use of melatonin as a pharmacological agent to prevent the agerelated decline in the immune system function and neutralize the adverse effects of stress has been extensively examined. In this sense, a number of studies support the immunoregulatory action of melatonin [4], with several in vivo and in vitro studies indicating that this indoleamine modulates certain immune functions and attenuates oxidative reactions in both mammals and birds [5,6]. In contrast to the number of studies using melatonin as an immunomodulatory agent, little attention has been paid to the possible effects that melatonin's precursor, the amino acid tryptophan, may exert, after its conversion into melatonin, on the immune system. Thus, it has been previously suggested that in mammals, the oral administration of tryptophan increases the plasma levels of melatonin, leading to an augmented innate immune response [7]. Particularly, the supply with the amino acid seems to stimulate the antigen ingestion of rat macrophages [8].In our previous work with the ringdove ( Streptopelia risoria ), we found a decline in phagocytosis with ageing, due at least in part to the absence of a circadian rhythm of melatonin in these animals; this was accompanied...

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 mgkg–1 body weight) were given to Wistar rats at 2-h intervals. Melatonin was injected intraperitoneally (25 mg kg–1 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.