Glucocorticoids in a Neonatal Hyperoxic Lung Injury Model: Pulmonary and Neurotoxic effects.

ABSTRACT

BACKGROUND: We aimed to compare the effect of dexamethasone (Dex), hydrocortisone (Hc), and methylprednisolone (Mpz) at equivalent doses on somatic growth, lung healing, and neurotoxicity in a hyperoxic rat model. We hypothesized that Mpz and Hc would be superior to Dex with less neurotoxicity by exerting similar therapeutic efficacy on the injured lung. METHODS: Neonatal rats were randomized to control, bronchopulmonary dysplasia (BPD), Dex, Hc, and Mpz groups. All drugs were administered daily following day 15 over 7 days. Histopathological and immunohistochemical analyses of the lung and brain were performed on day 22. RESULTS: All types had much the same impact on lung repair. Oxidative markers in the lung were similar in the steroid groups. While nuclear factor erythroid 2-related factor and heat-shock protein 70 dropped following steroid treatment, no difference was noted in other biochemical markers in the brain between the study groups. Apoptotic activity and neuron loss in the parietal cortex and hippocampus were noted utmost in Dex, but alike in other BPD groups. CONCLUSIONS: Mpz does not appear to be superior to Dex or Hc in terms of pulmonary outcomes and oxidative damage in the brain, but safer than Dex regarding apoptotic neuron loss. IMPACT This is the first study that compared the pulmonary efficacy and neurotoxic effects of Dex, Hc, and Mpz simultaneously in an established BPD model. This study adds to the literature on the importance of possible antioxidant and protective effects of glucocorticoid therapy in an oxidative stress-exposed brain. Mpz ended up with no more additional neuron loss or apoptosis risk by having interchangeable effects with others for the treatment of established BPD. Mpz and Hc seem safe as a rescue therapy in terms of adverse outcomes for established BPD in which lung and brain tissue is already impaired.