The impact of methotrexate on lung inflammatory and apoptotic pathway biomarkers—The role of gallic acid

• Published in: Biomedicine & pharmacotherapy 2016-12, Vol.84, p.1689-1696
• Main Authors: Saygin, Mustafa, Ozturk, Onder, Ozmen, Ozlem, Ilhan, Ilter, Gonca, Taner, Gumral, Nurhan, Orhan, Hikmet, Aslankoc, Rahime
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Biomarkers - metabolism; C-Reactive Protein - metabolism; Caspases - metabolism; Comet Assay; Dinoprostone - metabolism; Gallic acid; Gallic Acid - pharmacology; Gallic Acid - therapeutic use; Immunohistochemistry; Inflammation; Internal Medicine; Lung; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; Medical Education; Methotrexate; Methotrexate - adverse effects; Oxidative stress; Oxidative Stress - drug effects; Pneumonia - blood; Pneumonia - chemically induced; Pneumonia - drug therapy; Pneumonia - pathology; Rats, Wistar; Serum Amyloid A Protein - metabolism; Signal Transduction - drug effects; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2016.10.077

Abstract Backgrounds The aim of this study was to investigate the effects of methotrexate (MTX) on the lung via inflammatory and apoptotic pathway biomarkers and the role of gallic acid (GA). Methods In this study, twenty four male Wistar-Albino rats weighing 300–350 g were divided into 3 groups as follows; Control group (0.1 ml/oral saline, for 7 days + 2nd day i.p.). MTX group (20 mg/kg, single dose, on 2nd day). MTX + GA group (15 mg/kg, orally, for 7 days). Comet analysis, oxidant-antioxidant status, IMA were conducted. Histopathological analyses were evaluated. Results Comet assay on the blood, TOS and OSI values in the lung were increased in the group II compared with the control group (p < 0.05). GA significantly reduced the comet score and IMA levels in the blood, TOS and OSI values in the lung tissue in group III compared with group II (p < 0.05). Immunohistochemically PGE2 , TNF-α, CRP, serum SAA, Caspase 3 and Caspase 9 expressions significantly increased in group II compared with the control group (p < 0.001) and GA treatment ameliorated these parameters significantly in group III compared with group II (p < 0.001). Conclusions MTX caused oxidative stress and DNA damage in the blood tissue and caused oxidative damage, inflammation and apoptosis in the lung tissue.