Effects of Nicotinamide and Niacin on Bleomycin-Induced Acute Injury and Subsequent Fibrosis in Hamster Lungs

Abstract

Nicotinamide (500 or 250 mg/kg body wt) or niacin (100 or 50 mg/kg body wt) was administered to hamsters given an intratracheal injection of bleomycin (BLM). At 7 days after the BLM injection, when compared with BLM-control animals, both nicotinamide- and niacin-treated animals showed similar acute lung injury, recognized as increases in the wet-to-dry lung weight ratio, intraalveolar albumin concentration, inflammatory cell number, and elastase activity. At 30 days after the BLM injection, both nicotinamide and niacin attenuated the development of pulmonary fibrosis, as indicated by fewer fibrotic changes and a decreased amount of lung hydroxyproline. Histologic examination revealed that, compared with nicotinamide, niacin had more potent antifibrotic effects. Lung nicotinamide–adenine–dinucleotide (NAD) was less depleted in nicotinamide-treated animals than in BLM-control animals. Nicotinamide- and niacin-treated animals had more intraalveolar cells than the BLM-control animals. These findings suggest that the development of pulmonary fibrosis induced by BLM was prevented through maintaining NAD by the administration of nicotinamide or niacin. Since neither nicotinamide nor niacin attenuated the inflammatory response to acute lung injury, the amelioration of fibrosis by these treatments appears to be independent of the early events.

Key Words:

• pulmonary fibrosis
• nicotinamide
• niacin
• bleomycin
• hamster