The effects of paraquat and dexamethasone on neonatal rat lung : a morphological and biochemical study
Hunter, Gordon S.
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The accidental poisoning of man by the herbicide paraquat has resulted in death in many cases due to pulmonary complications characterized by fibrosis, loss of alveolar epithelium and insufficient levels of surfactant. Other chemical agents which affect the lung are the glucocorticoid hormones. When administered to fetal mammals the normal pattern of lung development is accelerated both morphologically and biochemically. It was of interest to study and compare the neonatal effects of paraquat and a synthetic glucocorticoid (dexamethasone) on a key enzyme for surfactant synthesis, phosphatidic acid phosphatase (PAPase) and attempt to correlate these biochemical changes with morphological alterations. One day old rat pups were injected (IP) with either 1 mg/kg body weight dexamethasone or 25 mg/kg body weight paraquat. After 24 hours the pups were sacrificed and the lungs removed for biochemical analysis (protein content, endogenous levels of inorganic phosphate and PAPase specific activity). There were no significant changes in body weight during the 24 hour exposure period within the control, dexamethasone or paraquat groups. The lung weight in the dexamethasone treated animals but not the paraquat group was significantly lower than those of the control. Histologically, the lungs from the dexamethasone group appeared normal but in the paraquat group there was much intra-alveolar infiltration of cells and cell debris with thick alveolar walls. Lung protein content increased with paraquat but decreased with dexamethasone. The enzymatic release of inorganic phosphate from phosphatidic acid was reduced in the paraquat group but unchanged in the dexamethasone group. These results indicate that paraquat induced both histological and biochemical changes in the neonatal rat lung while dexamethasone does not appear to affect the lung under these conditions.