Among other anti-inflammatory therapies, inhalation (aerosol) treatments with glutathione (GSH) have become popular in CF patients, with the aim of restoring bronchial fluids levels of this primary antioxidant. GSH is in fact consumed during inflammatory processes. The results obtained so far, however, remain disappointing. One of the possible reasons of such inefficiency may lie in the fact that CF lungs often present with increased levels of gamma-glutamyltransferase (GGT), an enzyme which is secreted by inflammatory cells, capable of degrading GSH. It has been shown (in cultured cells) that GSH degradation, besides consuming exogenously administered GSH, also originates metabolites having (paradoxically) a pro-inflammatory and harmful action. The present project takes into account this aspect for the first time. Experiments were made to clarify whether the presence of GGT activity in lung fluids of patients may represent a contraindication to employment of GSH inhalation. It was also verified whether the inhibition of GGT may suppress the pro-inflammatory effects and restore the antioxidant/beneficial action of GSH. A pioneering CF animal model has been employed. In addition, suitable laboratory analyses were carried out on samples obtained from CF patients during GSH inhalation treatment.
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