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

Abstract

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.

Keywords::

• Corticosterone
• diabetes
• melatonin
• neonatal
• stress

Acknowledgements

B.D.B and P.K.S acknowledge with thanks the fellowship from UGC under UGCRFSMS scheme. Thanks are due to Prof. T.G.Shrivastava, Immuno-Technology & Steroid Laboratory Department of Reproductive Biomedicine, NIHFW. Munirka, New Delhi for Progesterone kit which was a generous gift from him and for his guidance through the work and Dr. Sunil Shah, Dr. Sunil’s Laboratory, Baroda for his valuable suggestions and help.

Declaration of Interest: The authors report no conflicts of interest.