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ISDN2012_0284: GSH mediated antioxidant role of alpha lipoic acid (ALA) in arsenic induced developmental neurotoxicity
Author(s) -
Dhar P.,
Dixit S.,
Mehra Raj D.
Publication year - 2012
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2012.10.055
Subject(s) - new delhi , alpha lipoic acid , citation , medicine , library science , pathology , computer science , oxidative stress , metropolitan area
Department of Anatomy, All India Institute of Medical Sciences, Delhi 110029, India The effect of exogenous lipoic acid (ALA) was studied on antioxidant markers (GSH, SOD) and apoptotic proteins (BCl 2, Bax) in hippocampus of rat pups exposed to sodium arsenite (NaAsO2, 1.5 and 2.0 mg/kg body wt.) from postnatal day (PND) 4–15 by intraperitoneal (i.p.) route. On PND 16, the animals were sacrificed either by perfusion fixation or by cervical dislocation. The forebrain containing hippocampus was separated from the whole brain (perfusion fixed) and subjected to cryopreservation. Cryocut sections (25 m) were processed for immunohistochemical localization of apoptotic proteins (Bax and Bcl2) besides carrying out TUNEL staining. The hippocampus obtained from fresh brains was processed for estimation of antioxidant levels and Western Blotting. The GSH levels were significantly reduced in arsenic exposed groups and administration of ALA with NaAsO2 resulted in increased levels of GSH. The number of TUNEL +ive cells was significantly more in animals exposed to NaAsO2 alone as compared to animals receiving ALA simultaneously with NaAsO2. The immunoexpression of Bax was substantially less intense in hippocampal sections of animals receiving ALA with NaAsO2 than the animals exposed to NaAsO2 alone whereas Bcl 2 was intensely expressed in animals receiving ALA with NaAsO2. These observations were substantiated by the semiquantitative analysis of cumulative grey values (NIS Elements-AR 3.10). Densitometric analysis (Western blots) revealed restoration of Bax and Bcl2 protein ratio to optimal value in animals receiving ALA with NaAsO2. These observations suggest the role of exogenous ALA in ameliorating arsenic induced neurotoxicity through GSH generation.