CHRONIC GLUTATHIONE DEPLETION ALTERS EXPRESSION OF ENTERIC INHIBITORYNEUROCHEMICALS IN THE MOUSE

Antioxidants may delay or prevent neural diseases. Depletion of the no n-enzymatic antioxidant, glutathione, in a mouse model was produced by inhibiting its rate-limiting enzyme, gamma-glutamylcysteine synthetas e, for 7 weeks. Ileum and colon were obtained from treated and control (saline) mice. Glutathione levels and nicotineamide adenine dinucleot ide phosphate (NADPH) diaphorase activity were determined by spectroph otometric assays; vasoactive intestinal peptide (VIP) levels were meas ured 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 w as decreased in ileum compared to controls, while NADPH diaphorase act ivity was decreased in colon compared to controls. In this chronic mou se model, glutathione appeared to regulate expression of enteric inhib itory nerve cell products. (C) 1997 Elsevier Science Ireland Ltd.