Abstract
Melatonin is involved in a number of physiological and oxidative processes, including functional regulation in human milk. The present study investigated the mechanisms of action of melatonin and its effects on the functional activity of colostral phagocytes in diabetic women. Colostrum samples were collected from normoglycemic (N = 38) and diabetic (N = 38) women. We determined melatonin concentration, superoxide release, bactericidal activity and intracellular Ca2+ release by colostral phagocytes treated or not with 8-(Diethylamino) octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) and incubated with melatonin and its precursor (N-acetyl-serotonin-NAS), antagonist (luzindole) and agonist (chloromelatonin-CMLT). Melatonin concentration was higher in colostrum samples from hyperglycemic than normoglycemic mothers. Melatonin stimulated superoxide release by colostral phagocytes from normoglycemic but not hyperglycemic women. NAS increased superoxide, irrespective of glycemic status, whereas CMTL increased superoxide only in cells from the normoglycemic group. Phagocytic activity in colostrum increased significantly in the presence of melatonin, NAS and CMLT, irrespective of glycemic status. The bactericidal activity of colostral phagocytes against enterophatogenic Escherichia coli (EPEC) increased in the presence of melatonin or NAS in the normoglycemic group, but not in the hyperglycemic group. Luzindole blocked melatonin action on colostrum phagocytes. Phagocytes from the normoglycemic group treated with melatonin exhibited an increase in intracellular Ca2+ release. Phagocytes treated with TMB-8 (intracellular Ca2+ inhibitor) decreased superoxide, bactericidal activity and intracellular Ca2+ release in both groups. The results obtained suggest an interactive effect of glucose metabolism and melatonin on colostral phagocytes. In colostral phagocytes from normoglycemic mothers, melatonin likely increases the ability of colostrum to protect against EPEC and other infections. In diabetic mothers, because maternal hyperglycemia modifies the functional activity of colostrum phagocytes, melatonin effects are likely limited to anti-inflammatory processes, with low superoxide release and bactericidal activity.
Highlights
Diabetes is prevalent in young women and is increasingly related to maternal and child health issues, such as breastfeeding
Hyperglycemic and normoglycemic groups exhibited similar spontaneous superoxide release by colostral mononuclear phagocytes, which did not increase with phagocyte exposure to enterophatogenic Escherichia coli (EPEC)
Phagocytes stimulated with MLT and incubated with EPEC had higher superoxide release than those exposed to the bacteria alone (p,0.05), but MLT stimulation was not observed in the hyperglycemic group
Summary
Diabetes is prevalent in young women and is increasingly related to maternal and child health issues, such as breastfeeding. This suggests that the antioxidant systems of diabetic individuals are likely compromised by high glucose levels [25] Despite this evidence, studies on the functional activity of phagocytes in the colostrum of diabetic mothers, as well as the action of these defense cells on the gut of newborns and their interactions with melatonin are scarce. The biological activity of colostral MLT and its interactions with milk components is important because colostrum consists of a complete micro-environment, where the combined action of soluble and cellular components possibly plays a significant protective role against pathogens in newborn guts, especially considering infants of diabetic mothers who are highly susceptible to infections. Given the lack of information on this issue, the present study investigated the mechanisms of action of MLT and its effects on the functional activity of phagocytes in the colostrum of diabetic women
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