Inhibitory effect of caffeic acid phenethyl ester on bleomycine-induced lung fibrosis in rats.
BACKGROUND
Pulmonary fibrosis (PF) induced by anticancerogenic bleomycin (BLM) is one of the more common side effects encountered during cancer treatment. It has been suggested in the last decades that the main responsible agent in PF is reactive oxygen species which were generated also in normal physiological conditions in the human body. In this experimental study, we investigated the preventive or attenuating effects of caffeic acid phenethyl ester (CAPE) that has been demonstrated to have anti-inflammatory, cytocytatic, anticancerogenic, antiprolipherative and antioxidant effects on BLM-induced PF.


METHODS
Thirty-six Sprague-Dawley rats were divided randomly into four groups as sham operation, BLM, BLM + vitamin E (vit E), and BLM + CAPE groups. BLM (7.5 mg/kg, single dose) was applied intratracheally, and CAPE and vit E intraperitoneally in the appropriate groups. At the end of the fibrosis processes, lung tissues were removed and the levels of tissues hydroxyproline (OH-proline), malondialdehyde (MDA) and NO as well as the activities of superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) were determined. Also, the weights of the rats were recorded at 7th and 14th days of the experiments.


RESULTS
BLM application to the rats resulted in a significant increase in the OH-proline level as compared to the controls. Administration of CAPE and vit E led to the remarkable reduction of total lung OH-proline levels compared to the rats treated with BLM alone (p < 0.0001). There were a decreases in antioxidant enzyme (SOD and CAT) activities while an increase in MPO activity in BLM group was found vs. the control group (p < 0.0001). CAPE had a regulator effect on these parameters: the increase in CAT and SOD activities and the decrease in MPO activity were seen after CAPE application. NO, MDA and OH-proline levels were increased in BLM group vs. the control group. CAPE was more effective in decreasing the tissue levels of NO, MDA and OH-proline than vit E. MPO activity, as a good marker of neutrophil sequestration to the tissues, in the BLM group was decreased by CAPE approximately to the control group.


CONCLUSIONS
We suggest that CAPE is more effective on the prevention of BLM-induced fibrosis via antioxidant and free radical scavenger properties than vit E at the doses used in the present study. CAPE has some attenuating effects on BLM-induced PF affecting both oxidant and antioxidant systems as well as neutrophils sequestration.
Ozyurt
Hüseyin
H
Department of Biochemistry, Gaziosmanpasa University, Medical School, Arastirma Hastanesi, 60100 Tokat, Turkey. huseyinozyurt@hotmail.com
Söğüt
Sadik
S
Yildirim
Zeki
Z
Kart
Levent
L
Iraz
Mustafa
M
Armutçu
Ferah
F
Temel
Ismail
I
Ozen
Süleyman
S
Uzun
Ahmet
A
Akyol
Omer
O
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001761:Bleomycin / Q000009:adverse effects*; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology
D000975:Antioxidants; D002109:Caffeic Acids; D001761:Bleomycin; D014810:Vitamin E; D009569:Nitric Oxide; D008315:Malondialdehyde; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D006909:Hydroxyproline