Neonatal corticosterone programs for thrifty phenotype adult diabetic manifestations and oxidative stress: countering effect of melatonin as a deprogrammer.

OBJECTIVE: The present study assesses the thrifty phenotype response of neonatal corticosterone programming to a diabetogenic challenge in adult rats and the role of melatonin as a deprogrammer. METHODS: Neonates of both sexes, born of healthy male and female rats maintained under standard conditions of temperature and light, were separated and, equal number of pups was assigned to lactating mothers. Pups treated with either saline or corticosterone or, a combination of corticosterone and melatonin from postnatal day (PND) 2 to PND 14 and, at 120 days of age, six animals from each treatment group were rendered diabetic by alloxanization. Various serum and tissue parameters pertaining to glycaemic regulation, dyslipidemia, hepatic and renal distress and oxidative stress were analysed in adult rats of all groups. RESULTS: The results indicate compromised feed efficiency, hyperglycaemia, hypoinsulinemia, decreased glycogen content, elevated serum and tissue lipids and serum markers of hepatic and renal stress, together with increased lipid peroxidation, and decreased levels of non-enzymatic and enzymatic antioxidants in corticosterone programmed diabetic animals than in the non-programmed diabetic rats. However, treatment with melatonin simultaneously prevented to a significant extent the alterations in carbohydrate and lipid metabolism and oxidative stress. CONCLUSIONS: Melatonin is a potent deprogrammer of neonatal corticosterone programming effects and the adult thrifty phenotype alteration to a diabetogenic challenge.

Plasticity changes in adult metabolic homeostasis and tissue oxidative stress: neonatal programming by corticosterone and melatonin as deprogrammer.

OBJECTIVE: To evaluate the long-term plasticity changes induced by neonatal corticosterone programming on adult metabolic status and the deprogramming effect of melatonin. METHODS: Male and female Wistar rats were maintained under standard conditions and when mated females delivered pups, neonates of both sexes were separated and equal number of pups was assigned to lactating mothers. Pups treated with saline, corticosterone or a combination of corticosterone and melatonin from PND 2 to PND 14, were maintained until 120 days of age. Various serum and tissue parameters pertaining to glycaemic regulation, dyslipidemia, hepatic and renal distress and oxidative stress were analyzed in adult rats. RESULTS: Neonatal corticosterone exposure induced dyslipidemia, increased fed and fasting glucose levels, insulin resistance, lipid peroxidation, serum levels of insulin, corticosterone and hepatic and renal dysfunction markers and decreased the levels of enzymatic and non-enzymatic antioxidants, relatively more in males. Melatonin proved as an effective deprogrammer of corticosterone induced plasticity changes. CONCLUSIONS: Neonatal corticosterone exposure induces long lasting effects on adult physiology and metabolism. Concurrent treatment with melatonin effectively deprograms the changes.