Protective effect of aminoguanidine in a murine model of pulmonary fibrosis induced by bleomycin.
Aminoguanidine is a drug known for more than a century, which has been attracting increasing interest in recent years due to the discovery of new pharmacological properties. This study investigated the effects of aminoguanidine on the fibrotic response induced by intratracheal administration of bleomycin to rats. Three groups of animals were studied: Group A (n = 19) corresponded to the control group. Group B (n = 20) received 10 IU/kg bleomycin intratracheal, and Group C (n = 12) received the same amount of bleomycin as Group B followed by 50 mg/kg/day aminoguanidine bicarbonate for 4 weeks. Aminoguanidine led to significant reductions in total hydroxyproline content of the lungs in Group C compared to Group B (Group A: 1.83+/-0.14 mg x Group B: 3.46+/-0.36 mg x Group C: 2.09+/-0.22 mg). Morphometric collagen studies carried out on histological sections stained with Sirius red F3BA showed that aminoguanidine promoted a significant reduction of the area occupied by collagen in the axial and septal zones of the lungs (Axial region = Group A: 4.29+/-1.31% x Group B: 19.30+/-4.86% x Group C: 8.52+/-1.96%; Septal region = Group A: 0.15+/-0.06% x Group B: 0.61+/-0.21% x Group C: 0.15+/-0.06%). These results suggest that aminoguanidine is a potential therapeutic agent for the treatment and prevention of pulmonary fibrosis which is associated with different clinical conditions.
de Rezende
M C
MC
Pulmonary Division, Universidade Federal de São Paulo (UNIFESP), Brazil.
Martinez
J A
JA
Capelozzi
V L
VL
Simões
M J
MJ
Beppu
O S
OS
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D006909:Hydroxyproline / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D006146:Guanidines; D001761:Bleomycin; D003094:Collagen; D019001:Nitric Oxide Synthase; D006909:Hydroxyproline; C004479:pimagedine