title: Activation of neuronal nitric oxide synthase in cerebellum of chronic hepatic encephalopathy rats is associated with up-regulation of NADPH-producing pathway.
abstract: Cerebellum-associated functions get affected during mild hepatic encephalopathy (MHE) in patients with chronic liver failure (CLF). Involvement of nitrosative and antioxidant factors in the pathogenesis of chronic hepatic encephalopathy is an evolving concept and needs to be defined in a true CLF animal model. This article describes profiles of NADPH-dependent neuronal nitric oxide synthase (nNOS) and those of glutathione peroxidase and glutathione reductase (GR) vis-a-vis regulation of NADPH-producing pathway in the cerebellum of CLF rats induced by administration of thioacetamide (100 mg kg⁻¹ b.w., i.p.) up to 10 days and confirming MHE on Morris water maze tests. Significant increases in the expression of nNOS protein and nitric oxide (NOx) level coincided with a similar increment in NADPH-diaphorase activity in the cerebellum of CLF rats. Glutathione peroxidase and GR utilize NADPH to regenerate reduced glutathione (GSH) in the cells. Both these enzymes and GSH level were found to be static and thus suggested efficient turnover of GSH in the cerebellum of MHE rats. Relative levels of glucose-6-phosphate dehydrogenase (G6PD) vs. phosphofructokinase 2 (PFK2) determine the rate of pentose phosphate pathway (PPP) responsible to synthesize NADPH. The cerebellum of CLF rats showed overactivation of G6PD with a significant decline in the expression of PFK2 and thus suggested activation of PPP in the cerebellum during MHE. It is concluded that concordant activations of PPP and nNOS in cerebellum of MHE rats could be associated with the implication of NOx in the pathogenesis of MHE.
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Centre of Advanced Studies in Zoology, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Singh
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Trigun
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002531:Cerebellum / Q000378:metabolism*; D002908:Chronic Disease; D004789:Enzyme Activation / Q000502:physiology; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning; D009249:NADP / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D009249:NADP; D052248:Nitric Oxide Synthase Type I
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