The effect of melatonin on bleomycin-induced pulmonary fibrosis in rats.
The present investigation was designed to determine the protective effects of melatonin against bleomycin (BLM)-induced oxidant lung toxicity. Wistar-albino rats were divided into four groups: saline (SA, 0.4 mL/animal), 1% ethanol-saline (ALC, 0.4 mL/animal), bleomycin sulphate (BLM, 10 mg/kg), or bleomycin sulphate + melatonin (BLM, 10 mg/kg + MLT, 10 mg/kg). All injections were given intraperitoneally (i.p.), twice weekly for a period of 3 wk (a total of seven injections for each group). Twenty-five days after BLM treatment, pulmonary fibrosis was assessed as hydroxyproline content in lung homogenates. Findings show that BLM-induced pulmonary injury resulted in increases in bronchoalveolar lavage fluid (BALF) biomarkers including total protein, lactate dehydrogenase (LDH), glutathione-peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT). Additionally, the levels of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation (LPO), were also increased in BALF. Conversely, the level of glutathione (GSH) was reduced in BALF of BLM-treated rats. Melatonin provided protection against BLM-induced pulmonary fibrosis by suppressing oxidative stress. It abolished BLM-stimulated LPO and reversed the imbalance between oxidants and antioxidants in the BALFs. Results thus indicate that melatonin inhibits BLM-induced lung toxicity associated with oxidative damage.
Arslan
Seyfullah O
SO
Department of Pharmacology, Faculty of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey. soarslan@lycos.com
Zerin
Mustafa
M
Vural
Huseyin
H
Coskun
Ali
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism; D001761:Bleomycin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D001761:Bleomycin; D008550:Melatonin