Abstract
Background: The effects of maternal exposure to glucocorticoids during gestation on various organs in the offspring have been reported in literature. There is paucity of information on the effects of maternal glucocorticoids treatment during lactation on organ functions in the offspring. The present study was designed to investigate the changes in kidney function and oxidative stress biomarkers in offspring of dams treated with dexamethasone during lactation in Wistar rats
Methods: Twenty pregnant rats (180-200g) were divided into 4 groups (n=5). Group 1 was administered 0.02ml/100g/day of normal saline (subcutaneously, s.c) at lactation days 1-21 (control). Groups 2,3, and 4 were administered 100 µg/kg/day dexamethasone (Dex) (s.c) at lactation days 1-7 (Dex1-7),1-14(Dex1-14), and 1- 21(Dex1-21) respectively. Evaluation of serum creatinine, urea and markers of oxidative stress in the kidney and histopathology of the kidney were carried out at 12 weeks of postnatal life.
Results: Serum creatinine and urea levels were significantly (p<0.05) higher in the Dex1-7, Dex1-14and Dex1-21 when compared with the control. Kidney MDA level was also significantly (p<0.05) increased in the Dex1-7, Dex1- 14 and Dex1-21groups when compared with the control. Kidney SOD activities, catalase activities and protein in the treatment groups Dex1-7, Dex1-14 and Dex1-21 were all significantly (p<0.05) lower than the control. Histology of the kidney showed mild, moderate and severe tubular necrosis in the Dex1-7, Dex1-14 and Dex1-21 groups respectively.
Conclusion: Results suggest that maternal exposure to dexamethasone during lactation may lead to increase oxidative stress in the kidney and increase renal necrosis.
Keyword: Dexamethasone, Serum analyte, Oxidative Stress, Lactation
Résumé
Contexte: Les effets de l'exposition maternelle aux glucocorticoïdes pendant la gestation sur divers organes dans la descendance ont été rapportés dans la littérature. Il y a pénurie d'informations sur les effets du traitement de glucocorticoïdes pendant l'allaitement maternel sur les fonctions d'organes dans la descendance. La présente étude a été conçue pour étudier les changements dans la fonction rénale et le stress oxydatif des marqueursbiologiquesdans les descendants des mères traitées avec la dexaméthasone pendant la lactation chez des rats Wistar.
Méthodes: Vingt rattes enceintes (180-200 g) ont été divisés en 4 groupes (n = 5). Groupe 1 a été administré 0,02 ml / 100 g / jour de solution saline normale (sous-cutanée, s.c.) aux jours de lactation 1-21 (contrôle). Groupes 2,3 et 4 ont été administrés 100 µg / kg / jour de la dexaméthasone (Dex) (s.c.) aux jours de lactation 1-7 (Dex1-7), 1-14 (Dex1- 14) et 1-21 (Dex1- 21), respectivement. L'évaluation de la créatinine sérique, l'urée et des marqueurs de stress oxydatif dans le rein et l'histopathologie du rein ont été effectuées à 12 semaines de la vie post-natale.
Résultats: Les taux de créatininesérique et de l'urée étaient significativement (p <0,05) plus élevés dans le Dex1-7, Dex1-14and Dex1-21 par rapport au contrôle. Le taux MDA durein a également été significativement (p <0,05) augmenté dans les groupes Dex1-7, et Dex1-14 Dex1-21 par rapport au témoin. Les activitésSOD du rein, les activitéscatalase et protéine dans les groupes de traitement Dex1-7, Dex1-14 et Dex1-21 étaient significativement (p <0,05) inférieure à celle du témoin. L'histologie du rein a montré une nécrose tubulaire légère, modérée et sévère dans les groupes Dex1-7, Dex1-14 et Dex1-21 respectivement.
Conclusion: Les résultats suggèrent que l'exposition maternelle à la dexaméthasone pendant l'allaitement peut entraîner une augmentation du stress oxydatif dans le rein et augmenter la nécrose rénale.
Mot-clé: Dexaméthasone, Analyse Sérique, Stress Oxydatif, Allaitement
Correspondence: Dr. Sikirullai O. Jeje, Department of Physiology, Cross River University of Technology, Okuku Campus, Cross Rivers State, Nigeria. E-mail: dhikrilat@yahoo.com
References
Tegethoff M, Pryce C and Manischmidt G. Effects of intrauterine exposure to synthetic glucocorticoids on fetal, Newborn and Infant HPA axis function in Humans: A Systematic Review. Endrocrine Review 2009; 30 (7): 753-789.
Drake AJ, Walker BR and Seckl JR. Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats. Am J Physiol Regul Integr Comp Physiol. 2005; 288:R34–R38.
Singh RR, Cuffe JSM and Moritz KM. Short and long term exposure to natural and synthetic glucocorticoids during development. Proceeding of Australian Physiological Society 2012; 43; 57-69..
Wang Y, Huang C and Hsu K. The role of growth retardation in lasting effects of neonatal dexamethasone treatment on hippocampal synaptic function Plos one 2010; 5(9) e12809 Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50–60 years. Br Med J.1996; 312:406–410..
Kapoor A, Dunn E, Kostak A, Andrews MH and Mathews SG. Fetal programming of hypothalamo-pituitary adrenal function: prenatan stress and glucocorticoids.The journal of Physiology. 2006; 572: 31-44.
Ahlbom E, Gogvadze V, Chen M, Celsi G and Ceccatelli S. Prenatal exposure to high levels of glucocorticoids increases susceptibility of cerebellar granules cell to oxidative stress induced cell death. PNAS. 2000;97 (26): 14726-14730.
Orzechowski A. Grizand J. Jank M. et al., Dexamethasone-mediated regulation differentiation of muscle cells, is hydrogen peroxide involved in the process?.Repro.Nutr. Dev.2002; 42: 197-218
Mcintosh, TK, Saatman KE, Raughupathi R. et al., The Dorothy Ressel memorial lecture. The molecular and cellular sequelae of experimental traumatic brain injury: pathologic mechanism. Neuropatholapplneurobiol.1998; 24 (4): 251-267.
Collins AR. Assays for oxidative stress and antioxidant status: applications to research into biological effectiveness of polyphenol. Am J. Clin Nutri. 2005;81(1): 2615- 2675.
Tilbrook AJ, Turner AI, Ibbot MD and Clark IJ, Activation of the hypothalamo-pituitary-adrenal axis by isolation and restrain stress during lactation in Ewes: effect of presence of lamb and suckling. Endocrinology. 2006;147(7): 3501-3509.
Beuge JA, and Aust SD. Microsomal lipid peroxidation. Meth. Enzymol. 1978; 52; 302–310.
Sinha KA. Colorimetric assay of catalase.Anal.Biochem. 1971:47: 389–394.
Misra HP and Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J. Biol. Chem.1972; 247(10): 3170–3175.
Lowry OH, Rosebrough NJ, Farr AL and Randall RJ. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 1951;193, 265–275.
Ganong WF. Review of Medical Physiology 22nd edition. McGraw Hill.2005.
Omotosho IO. Evaluation of urinary N-acetyl-]”-D-glucosaminidase (NAG) and Glutathione-S-tranferase (GST) activities as early markers of occupational lead nephropathy in an African population. Arch. Bas. App. Med. 2013; 1: 87-91.
Woods LL and Weeks DA. Prenatal programming of adult blood pressure: role of maternal corticosteroids. Am.J. Physiol. Regul. Integr. Comp. Physiol.2005;289: R955-962.
Ozbek E. Induction of oxidative stress in kidney. Inter. J. of nephrol. 2012; ID 465897 pg1-9.
Wu Defeng and Cederbaum Arthur I. Alcohol, oxidative stress and free radicals damage. Alcohol Research and Health. 2003; 27( 4): 277-284.