Effects of niacin on bleomycin-induced increases in myeloperoxidase, prolyl hydroxylase, and superoxide dismutase activities and collagen accumulation in the lungs of hamsters.
It has been shown that lung nicotinamide adenine dinucleotide (NAD) depletion accompanies bleomycin (BL)-induced lung fibrosis in the hamster and that treatment with niacin (NA), a precursor of NAD, was found to attenuate lung fibrosis caused by this agent. Niacin was used in the present study to investigate changes in some biochemical parameters and enzymes involved in the development of BL-induced lung fibrosis in the hamster. Niacin (500 mg/kg, IP), or an equivalent volume of saline (SA, IP), was given daily 2 days prior to intratracheal instillation of BL (7.5 U/5 mL/kg) or SA and everyday thereafter throughout the study. Hamsters were killed at 1, 4, 7, 10, and 14 days after the BL or SA instillation and their lungs processed for various biochemical assays. Hydroxyproline content and superoxide dismutase (SOD) activity in SABL treated animals were significantly (P < or = 0.05) elevated at 7 and 10 days, peaking at 14 days to 161 +/- 11% and 159 +/- 11% of the SASA treated animals, respectively. Although the hydroxyproline level of NABL treated animals was significantly elevated at 7 and 10 days and peaked at 14 days to 123 +/- 8% of the NASA control, these values were significantly lower than the SABL treated animals at the corresponding times. The lung SOD activity of NABL groups was significantly higher at 4 days but significantly lower at 10 and 14 days than the SABL groups at the corresponding times. Prolyl hydroxylase (PH) activity and total lung calcium in SABL treated groups were significantly elevated compared to SASA treated groups starting at 4 days, with PH peaking at 10 days to 163 +/- 13% and calcium peaking at 7 days to 148 +/- 8% of SASA treated groups. The NABL treated animals displayed a significant elevation in PH activity at 4 days only (132 +/- 15%), while the calcium content in this group was significantly increased at 4 and 14 days compared to NASA treated animals. However, the activity of PH in the NABL treated animals was significantly lower than the SABL treated animals at 7, 10, and 14 days. The calcium content of the NABL group was significantly lower than the SABL group at 7 and 10 days. The thiobarbituric acid reactive substance equivalents (TBARS) content and myeloperoxidase (MPO) activity were significantly elevated at all time points in SABL groups as compared to SASA groups, with peak elevation of TBARS to 160 +/- 9% at 4 days and MPO to 268 +/- 40% at 1 day.(ABSTRACT TRUNCATED AT 400 WORDS)
O'Neill
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Department of Veterinary Pharmacology and Toxicology, University of California, Davis 95616.
Giri
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D000818:Animals; D001761:Bleomycin / Q000037:antagonists & inhibitors*; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000187:drug effects; D006224:Cricetinae; D006909:Hydroxyproline / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009525:Niacin / Q000494:pharmacology*; D009195:Peroxidase / Q000187:drug effects; D011393:Procollagen-Proline Dioxygenase / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances
D017392:Thiobarbituric Acid Reactive Substances; D001761:Bleomycin; D009525:Niacin; D003094:Collagen; D009195:Peroxidase; D011393:Procollagen-Proline Dioxygenase; D013482:Superoxide Dismutase; D006909:Hydroxyproline; D002118:Calcium