Chronic glutathione depletion alters expression of enteric inhibitory neurochemicals in the mouse.
Antioxidants may delay or prevent neural diseases. Depletion of the non-enzymatic antioxidant, glutathione, in a mouse model was produced by inhibiting its rate-limiting enzyme, gamma-glutamylcysteine synthetase, for 7 weeks. Ileum and colon were obtained from treated and control (saline) mice. Glutathione levels and nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity were determined by spectrophotometric assays; vasoactive intestinal peptide (VIP) levels were measured by radioimmunoassay. Glutathione levels were higher in ileum than colon. Colonic glutathione was decreased in treated mice compared to controls; there were no differences in ileal glutathione levels. VIP was decreased in ileum compared to controls, while NADPH diaphorase activity was decreased in colon compared to controls. In this chronic mouse model, glutathione appeared to regulate expression of enteric inhibitory nerve cell products.
Koch
T R
TR
Department of Medicine, LA Johnson VA Medical Center, West Virginia University, Morgantown 26506-9161, USA.
Fink
J G
JG
Ruan
E
E
Petro
A
A
Opara
E C
EC
D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D003106:Colon / Q000378:metabolism; D017615:Enteric Nervous System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D011863:Radioimmunoassay; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D004791:Enzyme Inhibitors; D014660:Vasoactive Intestinal Peptide; D019328:Buthionine Sulfoximine; D009252:NADPH Dehydrogenase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione