We tested the efficacy of 2
antifibrotic agents, the
proline analogue cis-4-hydroxy-L-proline (cHyp) and the lathyrogen
beta-aminopropionitrile (
BAPN), on experimental
silicosis in hamsters.
Silica (75 mg) was instilled intratracheally, and 3 months later lung
hydroxyproline content, the volume density of silicotic nodules in lung parenchyma, fluid-filled lung pressure-volume curves,
body weight and survival were measured. Animals were injected with cHyp, 200 mg/kg
body weight, or
BAPN, 150 mg/kg
body weight, twice daily for 3 months.
Hydroxyproline contents (mg/lung) at 3 months were: control, 0.8 +/- 0.1;
silica, 1.4 +/- 0.1 (P less than 0.05 compared to control);
silica-cHyp, 1.2 +/- 0.2;
silica-
BAPN, 1.4 +/- 0.1 (both NS compared to
silica). The volume density of
granuloma (% of surface area) was:
silica, 0.7 +/- 0.1;
silica-cHyp, 5.9 +/- 1.0;
silica-
BAPN, 9.7 +/- 1.5 (both P less than 0.5 compared to
silica). There was no difference among the groups as assessed by lung pressure-volume curves. No toxic effects were produced on the skeletal system as assessed by bone
hydroxyproline content and skeletal roentgenograms. Final
body weights (g) were:
silica, 114 +/- 5;
silica-
BAPN, 108 +/- 6;
silica-cHyp, 88 +/- 7 (the latter P less than 0.05 compared to
silica). Survival (%) was:
silica, 62%;
silica-
BAPN, 34%,
silica-cHyp, 28% (both P less than 0.05 compared to
silica). These data show that cHyp and
BAPN treatment did not prevent
silica-induced
pulmonary fibrosis, led to more extensive silicotic nodules, and were toxic. Both cHyp and
BAPN have some efficacy in other models of
fibrosis, and the observations in the present study could be specific to
silicosis in the hamster.