Attenuation of bleomycin-induced lung fibrosis in rats by mesna.
Lung fibrosis is a common side effect of the chemotherapeutic agent, bleomycin. Current evidence suggests that reactive oxygen species may play a key role in the development of lung fibrosis. The present study examined the effect of mesna on bleomycin-induced lung fibrosis in rats. Animals were divided into three groups: (1) saline control group; (2) Bleomycin group in which rats were injected with bleomycin (15 mg/kg, i.p.) three times a week for four weeks; (3) Bleomycin and mesna group, in which mesna was given to rats (180 mg/kg/day, i.p.) a week prior to bleomycin and daily during bleomycin injections for 4 weeks until the end of the treatment. Bleomycin treatment resulted in a pronounced fall in the average body weight of animals. Bleomycin-induced pulmonary injury and lung fibrosis was indicated by increased lung hydroxyproline content, and elevated nitric oxide synthase, myeoloperoxidase, platelet activating factor, and tumor necrosis factor-alpha in lung tissues. On the other hand, bleomycin induced a reduction in reduced glutathione concentration and angiotensin converting enzyme activity in lung tissues. Moreover, bleomycin-induced severe histological changes in lung tissues revealed as lymphocytes and neutrophils infiltration, increased collagen deposition and fibrosis. Co-administration of bleomycin and mesna reduced bleomycin-induced weight loss and attenuated lung injury as evaluated by the significant reduction in hydroxyproline content, nitric oxide synthase activity, and concentrations of myeoloperoxidase, platelet activating factor, and tumor necrosis factor-alpha in lung tissues. Furthermore, mesna ameliorated bleomycin-induced reduction in reduced glutathione concentration and angiotensin activity in lung tissues. Finally, histological evidence supported the ability of mesna to attenuate bleomycin-induced lung fibrosis and consolidation. Thus, the findings of the present study provide evidence that mesna may serve as a novel target for potential therapeutic treatment of lung fibrosis.
El-Medany
Azza
A
Department of Pharmacology, College of Medicine and KHUH, King Saud University, P.O. BOX 2925, Riyadh 11461, Saudi Arabia.
Hagar
Hanan H
HH
Moursi
Mahmoud
M
At Muhammed
Raeesa
R
El-Rakhawy
Fatma I
FI
El-Medany
Gamila
G
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D006909:Hydroxyproline / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D015080:Mesna / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D019001:Nitric Oxide Synthase / Q000737:chemistry / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D010972:Platelet Activating Factor / Q000187:drug effects / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A; D005978:Glutathione; D015080:Mesna; D006909:Hydroxyproline