Farnesol attenuates lipopolysaccharide-induced neurodegeneration in Swiss albino mice by regulating intrinsic apoptotic cascade.
Neuronal apoptosis occurs as a sequel of oxidative stress associated with various neuropathies. In this study, we have investigated the protective effect of farnesol, a sequisterpene on lipopolysaccharide (LPS) induced neurodegeneration through modulation of intrinsic apoptotic cascade in the cortex and hippocampus of Swiss albino mice. Intraperitoneal (i.p.) injection of LPS (250 μg/kg b.wt. for 7 days) resulted in elevated levels of lipid peroxidation, protein carbonyls and 8-Hydroxydeoxyguanosine (8OHdG), with subsequent depletion in the antioxidant status and severe histological aberrations. These anomalies were accompanied by increased expressions of pro-apoptotic Bax, caspase-3 and p53 with decrease in anti-apoptotic Bcl-2. Farnesol treatment (100mg/kg b.wt.) ameliorated LPS-induced oxidative stress by enhancing the antioxidant defense system as evident from the increased levels of SOD, CAT, GSH and GST and exhibited protected cellular morphology manifested from histopathological and nissl staining analyses. Farnesol treatment also reduced the expulsion of cytochrome c from mitochondria and downregulated caspase 3 activation as revealed by immunoblot analysis. Furthermore, farnesol treatment reduced the expression of Bax and antagonized LPS-induced decrease in anti-apoptotic Bcl-2. Results of this study show that farnesol exerts neuroprotective effect by regulating intrinsic apoptotic cascade through its antioxidant effect during LPS-induced neurodegeneration.
Department of Biochemistry, Cell Biology Laboratory, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India.
Rajasekaran
R
Santhanasabapathy
Department of Biochemistry, Cell Biology Laboratory, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India. Electronic address: sudhandiran@yahoo.com.
Ganapasam
G
Sudhandiran
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004926:Escherichia coli; D005204:Farnesol / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation
D000975:Antioxidants; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D005204:Farnesol
Apoptosis; Farnesol; Lipopolysaccharide; Neurodegeneration; Oxidative stress