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Taurine and niacin have been previously found to block the accumulation of collagen in lung in the multidose bleomycin hamster model of pulmonary fibrosis. Previous studies have found an increase in the pulmonary collagen cross-links dihydroxylysinonoroleucine (DHLNL) and hydroxypyridinium (OHP) in the single dose bleomycin rat model. In this study, we asked if taurine and niacin would block the increase in DHLNL and OHP in the multidose bleomycin hamster model of lung fibrosis. Hamsters were intratracheally instilled with three consecutive doses of saline or bleomycin sulfate 1 week apart (2.5, 2.0, 1.5 units/5 mL/kg). Animals were fed diet containing either 2.5% niacin and 2.5% taurine or control diet throughout the experiment. The four groups were saline-instilled with control diet (SCD), bleomycin instilled with control diet (BCD), bleomycin-instilled with taurine-niacin in diet (BTN), and saline-instilled with taurine-niacin in diet (STN). Animals were sacrificed at 1, 4, and 8 weeks after the last bleomycin instillation. Hydroxyproline per lung in the BCD group was significantly elevated by 38, 56, and 60% over the SCD group at 1, 4, and 8 weeks, respectively. There were no statistically significant differences among the four groups in DHLNL (mmole) per mole collagen at the 1 or 8 week time point. At four weeks, DHLNL was significantly elevated by 46.4% in the BCD group over the SCD group. The OHP (mmole) per mole of collagen at 1 and 4 weeks in the BCD group was not statistically different from the SCD group.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraperitoneal administration of 50 mg/kg paraquat dichloride to mice significantly increased pulmonary vascular permeability at 24 and 48 hr, as measured by 125I-albumin content of alveolar lavage. Lung edema, measured by lung weight as percent body weight, was significantly increased 48 hr after paraquat treatment. Intravenous administration of four doses of superoxidase dismutase at 12-hr intervals (i.e., one before and three after paraquat treatment) failed to inhibit paraquat-induced increased pulmonary vascular permeability and pulmonary edema. Superoxide dismutase treatment also failed to reduce mortality and had no significant effect on the death time course in animals challenged with paraquat. The results of this study suggest that acute toxic effects of paraquat, such as increased pulmonary vascular permeability and pulmonary edema, may not be mediated through the generation of superoxide anion.