Mechanism of antifibrotic effect of taurine and niacin in the multidose bleomycin-hamster model of lung fibrosis: inhibition of lysyl oxidase and collagenase.
In the multiple-dose bleomycin-hamster model of pulmonary fibrosis, combined treatment with taurine and niacin blocks the increase in lung collagen deposition. We investigated the effects of taurine and niacin on lung lysyl oxidase and type I collagenase activities in this model. Hamsters were intratracheally instilled with three weekly doses of saline or bleomycin sulfate. Animals were fed either a diet containing 2.5% niacin and 2.5% taurine, or a control diet throughout the experiment. The four groups were saline-instilled with the control diet (BCD), bleomycin-instilled with the diet containing taurine and niacin (BTN), and saline-instilled with the diet containing taurine and niacin (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. Lysyl oxidase activity per lung in the BCD group was significantly elevated by 57.5 and 91.4% over the SCD controls at 1 and 4 week time periods, respectively. Type I collagenase activity per lung in the BCD group was significantly elevated by 65 and 80% over the SCD controls at 1 and 4 weeks, respectively. The combined treatment with taurine and niacin abolished the bleomycin-induced increases in the lung hydroxyproline content and lysyl oxidase and collagenase activities. It was postulated that one of the mechanisms for the antifibrotic effect of taurine and niacin may be the blockage of bleomycin-induced increases in the lung lysyl oxidase and collagenase activities.
Blaisdell
R J
RJ
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis 95616, USA.
Giri
S N
SN
D000818:Animals; D001761:Bleomycin; D006224:Cricetinae; D006909:Hydroxyproline / Q000096:biosynthesis; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008647:Mesocricetus; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D013654:Taurine / Q000008:administration & dosage / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D001761:Bleomycin; D013654:Taurine; D009525:Niacin; D008249:Protein-Lysine 6-Oxidase; D006909:Hydroxyproline