Niacin attenuates bleomycin‐induced lung fibrosis in the hamster

Abstract

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.

Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin D2 Receptor Subtype 1

“…Next, we examined the effect of niacin on zymosan-induced peritonitis in mice. Niacin (600 mg/kg) (Wang et al, 1990;Nagai et al, 1994;Godin et al, 2012) was administered to mice 24 hours after zymosan challenge ( Fig. 2A), and peritoneal macrophages were isolated for geneexpression analysis.…”

Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

“…It is generally believed that niacin offers protection against tissue damage caused by a variety of oxidants by virtue of its ability to increase intracellular level of NAD and to inhibit overactivation of poly(ADP-ribose) polymerase (79,81). An overstimulation of this chromosomal enzyme leads to intracellular depletion of NAD (82).…”

“…The hamsters were randomly placed into four treatment groups: saline-instilled fed control diet (SA), bleomycin-instilled fed control diet (BL), bleomycin-instilled fed taurine-niacin in diet (TNBL), and saline-instilled fed taurine-niacin in diet (TNSA). The animals were intratracheally instilled with either three consecutive doses of bleomycin sulfate in saline, or saline 1 week apart (2.5, 2.0, and 1.5 U/5 ml/kg) under pentobarbital anesthesia (75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) mg/kg) as described by Zia et al (14).…”

Niacin requirements for genomic stability

“…Although rat lung NAD + levels are less than half of that in the liver [33], and although the PAR response to hyperoxia was blunted by niacin deficiency, there was no change in the measures of tissue injury due to niacin deficiency [13], suggesting that the decrease in PAR formation was not great enough to sensitize the lung to oxidant injury. Studies with more acute lung injury, using bleomycin, have shown that niacin supplementation, above requirement, can be protective [34].…”