Niacin attenuates bleomycin-induced lung fibrosis in the hamster.
Bleomycin (BLM)-induced lung fibrosis has been shown to be accompanied by the activation of poly(ADP-ribose) polymerase and depletion of nicotinamide adenine dinucleotide (NAD) in the lung. Niacin, a precursor of NAD, was used in the present study to investigate its possible ameliorating effect on BLM-induced pulmonary fibrosis in hamsters. Niacin (500 mg/kg IP) or saline (IP) was injected daily for 16 or 23 days. On day 3, hamsters were treated with BLM (7.5 U/5 mL/kg) or an equivalent volume of saline intratracheally. BLM alone significantly increased lung hydroxyproline levels, bronchoalveolar lavage fluid protein concentration, and various inflammatory cell counts in the lavage in both experiments. In addition, BLM alone elevated prolyl hydroxylase and poly(adenosine-5'-diphosphate [ADP]-ribose) polymerase activities in the 3-week study. Niacin treatment significantly decreased BLM-elevated lung hydroxyproline, prolyl hydroxylase, and poly(ADP-ribose) polymerase activities. Histopathology revealed that niacin treatment attenuated BLM-induced thickened alveolar septa, foci of fibrotic consolidation, and accumulations of inflammatory cells in the parenchyma and air spaces. The ability of niacin to attenuate BLM-induced lung fibrosis in hamsters suggests that it may have potential as an antifibrotic agent in humans.
Department of Veterinary Pharmacology, School of Veterinary Medicine, University of California, Davis 95616.
Q J
QJ
Wang
S N
SN
Giri
D M
DM
Hyde
J M
JM
Nakashima
I
I
Javadi
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D008168:Lung / Q000033:anatomy & histology / Q000201:enzymology / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D009243:NAD / Q000378:metabolism; D009525:Niacin / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000517:prevention & control
D011506:Proteins; D009243:NAD; D001761:Bleomycin; D009525:Niacin; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; C030606:proline, 2-oxoglutarate 3-dioxygenase; D011065:Poly(ADP-ribose) Polymerases