The enteroendocrine cells in gastrointestinal (GI) tract synthesize more than thirty hormones in mammals. Among these cells, the enterochromaffin (EC) cells are probably the most important one due to the fact that they produce melatonin. The rate-limiting enzymes for melatonin synthesis including arylalkylamine-N-acetyltransferase (AANAT, currently the SNAT) and hydroxyindole-O-methyltransferase (HIOMT, currently the ASMT) have been identified in EC cells and this has confirmed the local melatonin production in GI tract by these cells. EC cells play a critical role in regulation of gastrointestinal physiology, particularly, in protection of the GI tract from free radical attack and inflammatory reaction. GI tract is the major site exposed to the oxidative stress and inflammation because of the food residue metabolism and the presence of trillions of microbes including the pathological bacteria. Thus, it requires strong protection. Melatonin synthesized by the EC cells provides the onsite protection in GI tract since this molecule is the potent free radical scavenger and effective ant-inflammatory agent. In this review we summarize the available information regarding the structural and functional variability of the EC cells as well as their pathophysiological roles in the GI tract. The focus is given to the protective effects of melatonin produced by the EC cells on the oxidative stress, inflammation and microbiota balance in GI tract.
Exercise conducted at an optimum training load is usually beneficial for the overall health of an individual. However, an unaccustomed intense exercise carried out by untrained individuals or elite athletes during over-training and/or competition-related stress often bear inevitable cardiovascular risks. Although many alterations occurring in the cardiovascular system during exercise are the results of training adaptations, sudden cardiovascular deaths reported in competitive athletes is a matter of grave concern. Several oxidative biomarkers that depict the underlying structural and functional impairment of the myocardial tissue have been identified in the individuals subjected to extensive exercise. The exercise-mediated cardiomyopathy is free radical related and also associated with pro-inflammatory response. In this review we will highlight the possible role of melatonin in obviating irrevocable oxidative cardiovascular injury triggered by extensive exercise stress. Melatonin effectively reduces exercise-induced lipid peroxidation, restores natural cellular antioxidant pool and supresses the innate immune cascade reaction that, otherwise, jeopardize cardiovascular integrity. Melatonin blocks the IKK/IκB/NFκB signaling as well as suppress iNOS and COX-2 mediated inflammation in cardiac tissue. In addition, melatonin reduces blood lactate accumulation and accelerates glucose utilization, thereby, promoting energy metabolism in athletes during their training and competition. Physical exertion associated overheating and the resultant sympathetic outflow impede cardiovascular homeostasis. Melatonin not only attenuates the sympathomedullary stimulation but also protects the cardiac cells from the cytotoxic effect of catecholamines. The available information regarding the efficacy of melatonin in amelioration of exercise-driven oxidative insult in cardiac tissue has been discussed and summarized.
Non-alcoholic fatty liver disease (NAFLD) is caused by hepatic fat accumulation with a high prevalence globally, especially in Western countries in which individuals have excessive fat consumption. Prolonged intake of high dietary fat causes various diseases due to the imbalance of energy metabolism, which leads to obesity and other pathological conditions. Currently, the exact pathogenesis of NAFLD is still obscure. In this review, the potential etiologies for NAFLD will be discussed, including adipose tissue dysfunction, intrahepatic de novo lipogenesis, hepatic fat accumulation, insulin resistance, hepatic inflammation, inflammasome activation, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress. Melatonin is a potent antioxidant and anti-inflammatory molecule. It is also a regulator of lipid and glucose metabolism which is indicated by melatonin’s effects on weight loss, reduction of liver weight, blood levels of lipids, glucose and insulin, activities of hepatic enzymes, steatohepatitis, and fibrosis. Melatonin considerably reduces mitochondrial dysfunction and proinflammatory cytokines. Moreover, it downregulates NLRP3 and its associated downstream effectors of caspase-1, IL-1β, and IL-18 proteins. This review will update the molecular mechanisms behind high-fat diet induced hepatic dysfunction and the protective role of melatonin in NAFLD.
Adrenaline at high pharmacological doses may lead to oxidative damages in diverse organs including gut. In this study, we attempt to elucidate the potentially protective effects of melatonin on gastrointestinal (GI) tissue damages induced by adrenaline. Rats were injected (s.c.) with different doses (0.125, 0.25 and 0.50 mg/kg) of adrenaline bitartrate (AD) for 15 days with or without melatonin (2.5, 5 and 10 mg/kg; orally). The results showed that adrenaline caused massive histological and ultra-structural GI injuries and melatonin (20 mg/kg) effectively protected these injuries. The protective mechanisms are related to the antioxidant and anti-inflammatory activities of melatonin indicated by increased glutathione levels and antioxidant enzymes as well as decreased oxidative stress markers and pro-inflammatory cytokines in GI tissues. The signal pathways of melatonin include up-regulating expression of Nrf2, SIRT1 and Bcl2, while down-regulating NFκB, TNFα and Bax. Melatonin also targeted mitochondrial energy homeostasis and biogenesis by up-regulating expression of PGC1α, AMPKα and SOD2 and reduced leakage of cytochrome c. The SIRT1-NFκB and PGC1α-AMPKα signal transduction pathways seem to play the central roles involving in melatonin’s protective effects on gastric damages induced by the high doses of adrenaline.
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