Biomaterial Database

Amelioration of bleomycin-induced lung fibrosis by treatment with the platelet activating factor receptor antagonist WEB 2086 in hamsters. 1995

S N Giri, and A K Sharma, and D M Hyde, and J S Wild

Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis 95616, USA.

Therapeutic use of bleomycin, an antineoplastic drug, is complicated by the development of a dose-dependent lung toxicity leading to fibrosis. This study tested the effectiveness of a platelet activating factor (PAF) receptor antagonist, WEB 2086, against bleomycin (BLEO)-induced lung fibrosis in hamsters. The animals were assigned to four groups: (1) saline (SA) + SA, (2) WEB 2086 (WEB) + SA, (3) SA + BLEO, and (4) WEB + BLEO. Sterile isotonic saline or WEB 2086 (10 mg/kg IP) was administered daily for the duration of the study starting 2 days prior to intratracheal (IT) instillation of saline or bleomycin (2.5, 2.0, and 1.5 units/kg 5 mL-1) in three consecutive doses at weekly intervals. The animals were killed at 21 days after the last IT instillation and their lungs were processed for various studies. The lung hydroxyproline levels in SA + SA, WEB + SA, SA + BLEO, and WEB + BLEO groups were 932 +/- 31, 943 +/- 48, 1302 +/- 72, and 964 +/- 63 micrograms/lung, respectively. The lung myeloperoxidase (MPO) activity and malondialdehyde equivalent, an index of lipid peroxidation, in the corresponding groups were 10 +/- 2, 8 +/- 2, 14 +/- 3, and 5 +/- 1 units/lung and 93 +/- 7, 77 +/- 5, 102 +/- 8, and 75 +/- 6 nmol/lung, respectively. The lung prolyl hydroxylase activity in the WEB + SA, SA + BLEO, and WEB + BLEO groups was 130.1 +/- 7.7, 236.2 +/- 12.8, and 138.1 +/- 7.0% of the SA + SA control group (8.3 x 10(4) dpm/lung 30 min-1), respectively. Daily treatment with WEB 2086 caused significant (p < or = .05) reductions in the BLEO-induced increases in the lung hydroxyproline content, prolyl hydroxylase and MPO activities, lipid peroxidation, and acid phosphatase activity of the BALF supernatant. Although daily treatment with WEB 2086 reduced the bleomycin-induced increases in the BALF total and neutrophil cell counts, BALF supernatant protein, and morphometric estimates of the lesions, these parameters were not significantly different from those of the SA-BLEO group. Histopathologic studies revealed that there were no lesions of alveolar consolidation and fibrosis in the lungs of WEB + BLEO group as compared with the SA + BLEO group. The results suggest that PAF is involved in the BLEO-induced lung fibrosis and that PAF-receptor antagonist may therefore be potentially useful in the attenuation of lung fibrosis caused by bleomycin.

UI	MeSH Term	Description	Entries
D008054	Lipid Peroxides	Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.	Fatty Acid Hydroperoxide,Lipid Peroxide,Lipoperoxide,Fatty Acid Hydroperoxides,Lipid Hydroperoxide,Lipoperoxides,Acid Hydroperoxide, Fatty,Acid Hydroperoxides, Fatty,Hydroperoxide, Fatty Acid,Hydroperoxide, Lipid,Hydroperoxides, Fatty Acid,Peroxide, Lipid,Peroxides, Lipid
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008297	Male		Males
D008647	Mesocricetus	A genus in the order Rodentia and family Cricetidae. One species, Mesocricetus auratus or golden hamster is widely used in biomedical research.	Hamsters, Golden,Hamsters, Golden Syrian,Hamsters, Syrian,Mesocricetus auratus,Syrian Golden Hamster,Syrian Hamster,Golden Hamster,Golden Hamster, Syrian,Golden Hamsters,Golden Syrian Hamsters,Hamster, Golden,Hamster, Syrian,Hamster, Syrian Golden,Syrian Hamsters
D010972	Platelet Activating Factor	A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.	AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D011393	Procollagen-Proline Dioxygenase	A mixed-function oxygenase that catalyzes the hydroxylation of a prolyl-glycyl containing peptide, usually in PROTOCOLLAGEN, to a hydroxyprolylglycyl-containing-peptide. The enzyme utilizes molecular OXYGEN with a concomitant oxidative decarboxylation of 2-oxoglutarate to SUCCINATE. The enzyme occurs as a tetramer of two alpha and two beta subunits. The beta subunit of procollagen-proline dioxygenase is identical to the enzyme PROTEIN DISULFIDE-ISOMERASES.	Protocollagen Prolyl Hydroxylase,Procollagen Prolyl 4-Hydroxylase,4-Hydroxylase, Procollagen Prolyl,Dioxygenase, Procollagen-Proline,Hydroxylase, Protocollagen Prolyl,Procollagen Proline Dioxygenase,Procollagen Prolyl 4 Hydroxylase,Prolyl 4-Hydroxylase, Procollagen,Prolyl Hydroxylase, Protocollagen
D011658	Pulmonary Fibrosis	A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death.	Alveolitis, Fibrosing,Idiopathic Diffuse Interstitial Pulmonary Fibrosis,Fibroses, Pulmonary,Fibrosis, Pulmonary,Pulmonary Fibroses,Alveolitides, Fibrosing,Fibrosing Alveolitides,Fibrosing Alveolitis
D001761	Bleomycin	A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.	BLEO-cell,Blanoxan,Blenoxane,Bleolem,Bleomicina,Bleomycin A(2),Bleomycin A2,Bleomycin B(2),Bleomycin B2,Bleomycin Sulfate,Bleomycins,Bleomycinum Mack,Bléomycine Bellon,BLEO cell,BLEOcell,Bellon, Bléomycine,Mack, Bleomycinum,Sulfate, Bleomycin
D006224	Cricetinae	A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.	Cricetus,Hamsters,Hamster
D006909	Hydroxyproline	A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.	Oxyproline,4-Hydroxyproline,cis-4-Hydroxyproline,4 Hydroxyproline,cis 4 Hydroxyproline