Protective Effects of Alpha-Lipoic Acid on Methotrexate-Induced Oxidative Lung Injury in Rats.
OBJECTIVE
Oxidative stress is one of the major causes of methotrexate induced lung injury (MILI). Alpha-lipoic acid (ALA), which occurs naturally in human food, has antioxidative and anti-inflammatory activities. The aim of this study was to research the potential protective role of ALA on MILI in rats.


METHODS
Twenty one rats were randomly subdivided into three groups: control (group I), methotrexate (MTX) treated (group II), and MTX+ALA treated (group III). Lung injury was performed with a single dose of MTX (20 mg/kg) to groups 2 and 3. On the sixth day, animals in all groups were sacrificed by decapitation and lung tissue and blood samples were removed for histological examination and also measurement the levels of interleukin-1-beta (IL-1β), malondialdehyde (MDA), glutathione (GSH), tumour necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and sodium potassium-adenosine triphosphatase (Na+/K+ATPase).


RESULTS
In MTX group tissue GSH, Na+/K+ATPase activities were lower, tissue MDA, MPO and plasma IL-1?, TNF-? were significantly higher than the other groups. Histopathological examination showed that lung injury was less severe in group 2 according to group 3.


CONCLUSIONS
Oxidative damage of MTX in rat lung is partially reduced when combined with ALA.
a Department of Chest Disease , Kahramanmaras Sutcu Imam University Medical Faculty , Kahramanmaras , Turkey.
Huseyin
H
Arpag
b Department of Histology , Malatya Inonu University Medical Faculty , Malatya , Turkey.
Mehmet
M
Gül
c Department of Chest Diseases , Sakarya University Medical Faculty , Sakarya , Turkey.
Yusuf
Y
Aydemir
a Department of Chest Disease , Kahramanmaras Sutcu Imam University Medical Faculty , Kahramanmaras , Turkey.
Nurhan
N
Atilla
b Department of Histology , Malatya Inonu University Medical Faculty , Malatya , Turkey.
Birgül
B
Yiğitcan
d Department of General Surgery , Antalya Education and Research Hospital , Antalya , Turkey.
Tugrul
T
Cakir
e Department of Biochemistry , Public Health Laboratuary , Kütahya , Turkey.
Cemal
C
Polat
f Department of Pharmacology , Marmara University Medicine Faculty, Istanbul, Turkey and Near East University Faculty of Denstry , Nicosia , North Cyprus.
Özer
Ö
Þehirli
g Department of Thoracic Surgery , Kahramanmaras Sutcu Imam University , Kahramanmaras , Turkey.
Muhammet
M
Sayan
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008727:Methotrexate / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
D000975:Antioxidants; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D008063:Thioctic Acid; D009195:Peroxidase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D008727:Methotrexate
alpha-lipoic acid; injury; lung; methotrexate; oxidative stress; rat