Effects of Maternal Dexamethasone Exposure During Lactation on Metabolic Imbalance and Oxidative Stress in the Liver of Male Offsprings of Wistar Rats
Mots-clés :
Dexamethasone, Lactation, Oxidative Stress, Liver, offspringRésumé
Summary: It has been reported in human and animal studies that early exposure to glucocorticoids could retard growth and subsequent development of cardio metabolic diseases. Chronic exposure to glucocorticoids induced oxidative stress. Therefore, the role of oxidative stress in some of the observed metabolic imbalance needs to be elucidated. This study examined the effects of lactational dexamethasone exposure on metabolic imbalance and oxidative stress marker in the liver of male offspring of exposed mother. Twenty lactating dams were divided into 4 groups of 5 animals each. Group 1 was administered 0.02 ml/100gbwt/day normal saline through lactation days 1-21. Group 2, 3, and 4 were administered 100 μg/kgbwt/day dexamethasone for lactation days 1-7, 1-14, and 1-21 respectively. The male offspring were thereafter separated and sacrificed at 12weeks of age for evaluation of lipid profile and oxidative stress marker in the liver.
Results from this study indicate that Total Cholesterol (TC), Triglycerides (TAG) and LDL- cholesterol (LDL-C) were significantly (p<0.001) higher in the Dex 1-7, Dex 1-14 and Dex 1-21 groups when compared with the control. HDL-Cholesterol (HDL-C) was significantly (p<0.001) reduced in the Dex 1-7, Dex 1-14 and Dex 1-21 groups relative to the control. Basal Fasting Blood Sugar (FBS) was also significantly (p<0.001) higher in the Dex 1-14 and Dex 1-21 groups when compared with the control. Liver malondialdehyde was significantly (p<0.001) higher in the Dex1-14 and Dex1-21 group compared to the control. However, liver catalase and SOD activity were all significantly (p<0.001) lower in Dex 1-7, Dex 1-14 and Dex 1-21 groups relative to control. Liver protein was significantly (p<0.001) lower in the Dex1-14 and Dex1-21 treatment groups when compared with the control. Findings from this study suggest that there is possible increase in metabolic imbalance in the offspring of mother exposed to dexamethasone during lactation and these effects may be secondary to increase oxidative stress in the liver.
Références
Ahlbom E, Gogvadze V, Chen M, Celsi G, and Ceccatelli S.(2000); Prenatal exposure to high levels of glucocorticoids increases susceptibility of cerebellar granules cell to oxidative stress induced cell death. PNAS ; 97 (26) 14726-14730
Aron DC. Finding JW, Tyrrell JB (2007) Glucocorticoids and adrenal androgen; Greenspan’s Basic and Clinical (David and Shoback) 8th edition
Barker DJ, Gluckman PD, Godfrey KM, Harding JE, Owens JA, and Robinson JS. (1993) Fetal nutri-tion and cardiovascular disease in adult life. Lancet 341: 938–941,
Berry MA, Abrahamowicz M, Usher RH (1997). Factors associated with growth of extremely premature infants during initial hospitalization. Pediatrics.;100:640–646.
Beuge, J.A., Aust, S.D., 1978. Microsomal lipid peroxidation. Meth. Enzymol. 52, 302–310.
Brindley, D.N.(1995); Role of glucocorticoids and fatty acids in the impairment of lipid metabolism observed in the metabolic syndrome. Int J Obes Relat Metab Disord;19(Suppl. 1): S69– 75.
Celsi and Aperia (1999); in Pediatric Nephrology eds. Baratt T Auner E and Harrison W. (Williams and Wilkins Baltimore) PP 101-106
Collins, A.R. (2005); Assays for oxidative stress and antioxidant status: applications to research into biological effectiveness of polyphenol. Am J. Clin Nutri. 81(1) 2615- 2675 Coyle, J.T and Puttfarken, 1993; Oxidative stress, glutamate and neurodegerative disorder Science 262 (5134) 689-695.
Drake AJ, Walker BR & Seckl JR (2005). Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats. Am J Physiol Regul Integr Comp Physiol 288, R34–R38
Ettinger Jr WH, Hazzard WR (1988). Prednisone increases very low density lipoprotein and high density lipoprotein in healthy men. Metabolism;37:1055–8. Hales, C.N. Barker, D.J. Clark, P.M. Cox, L.J. Fall, C. Osmond, C. Winter, PD. (1991) Fetal and infant growth and impaired glucose tolerance at age 64. Br Med J 303:1019– 1022. Huang CC, Lin HR, Liang YC, Hsu KS (2007). Effects of neonatal corticosteroid treatment on hippocampal synaptic function. Pediatr Res.;62:267–270.
Iuchi ,T. Akaike. M, Mitgui, T et al, (2003); glucocorticoids excess induces superoxide production in vascular endothelial cells and elicit vascular endothelial dysfunction. Circulation Research 92: 81-87
Kapoor. A., Dunn.E., Kostak. A., Andrews MH, Mathews SG (2006): Fetal programming of hypothalamo-pituitary adrenal function: prenatan stress and glucocorticoids; The journal of physiology, 572, 31-44
Leitch CA, Ahlrichs J, Karn C, Denne SC (1999). Energy expenditure and energy intake during dexamethasone therapy for chronic lung disease. Pediatr Res.;46:109–113.
Lin HJ, Huang CC, Hsu KS (2006). Effects of neonatal dexamethasone treatment on hippocampal synaptic function. Ann Neurol.;59:939–951
Lithell, H.O. McKeigue, P.M. Berglund, L. Mohsen, R. Lithell, U.B. Leon, D.A. (1996),Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50–60 years. Br Med J 312:406–410.
Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265–275
Masharani U and German MS (2007) Pancreatic Hormone and Diabetes Mellitus Greenspan’s Basic and Clinical Endocrinology (David and Shoback) 8th edition
McIntosh, T.K. Saatman, K.E. Raughupathi, R. et al, (1998); The Dorothy Ressel memorial lecture. The molecular and cellular sequelae of experimental traumatic brain injury: pathologic mechanism. Neuropathol appl neurobiol 24 (4) 251-67
Misra, H.P., Fridovich, I., 1972. The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J. Biol. Chem. 247 (10), 3170– 3175.
Neal CR, Jr, Weidemann G, Kabbaj M, Vázquez DM (2004). Effect of neonatal dexamethasone exposure on growth and neurological development in the adult rat. Am JPhysiol Regul Integr Comp Physiol.;287:375–385
Orzechowski, A. Grizand, J. Jank, M. et al, (2002); Dexamethasone-mediated regulation differentia-tion of muscle cells, is hydrogen peroxide involved in the process?. Repro. Nutr. Dev. 42 197-218
Rainey, W.E. Rodgers, R.J. Mason, J.I. (1992) The
role of bovine lipoproteins in the regulation of steroidogenesis and HMG-CoA reductase in bovine adrenocortical cells. Steroids;57:167– 73.
Sapolsky, R.M. Romero, L.M. Munck. A.U. (2000); How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory and preparative actions. Endocr Rev;21: 55– 89.
Schafer, F.Q. Buettner, G.R. (2001). "Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple". Free Radic. Biol. Med. 30 (11): 1191–212.
Shrivastava A, Lyon A, McIntosh N (2000). The effect of dexamethasone on growth, mineral balance and bone mineralisation in preterm infants with chronic lung disease. Eur J Pediatr.;159:380–384
Sinha, K.A., 1971. Colorimetric assay of catalase. Anal. Biochem. 47, 389–394.
Singh RR.,Cuffe JSM., and Moritz KM.(2012). Short and long term exposure to natural and synthetic glucocorticoids during development. Proceeding of Australian Physiological Society 43: 57-69
Tilbrook A.J, Turner A.I, Ibbot M.D and Clark I.J, 2006; Activation of the hypothalamo-pituitary-adrenal axis by isolation and restrain stress during lactation in Ewes: effect of presence of lamb and suckling. Endocrinology; 147(7 ) pp 3501-3509
Wang Y, Huang C, Hsu K, (2010); the role of growth retardation in lasting effects of neonatal dexamethasone treatment on hippocampal synaptic function Plos one ; 5(9) e12809
Whitworth, J.A, Mango, G.J, Kelly D (2000); Cushing Cortisol and cardiovascular diseases. Hypertension 36: 912-916.
Téléchargements
Publié
Numéro
Rubrique
Licence
Cette œuvre est sous licence Creative Commons Attribution - Pas d'Utilisation Commerciale - Pas de Modification 4.0 International.
