Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats.
The aim of the current study was to investigate the probable protective effects of Pentoxifylline (PTX) and Alpha Lipoic Acid (ALA), which display anti-oxidative efficacy against hepatotoxicity and nephrotoxicity, those being the major side effects of Methotrexate (MTX). Rats were divided into four groups: a control group; MTX (20mg/kg/day) group; MTX+PTX (20mg/kg/day+50mg/kg/day) group; and an MTX+ALA (20mg/kg/day+100mg/kg/day) group. At the end of the experiment, biochemical, histochemical and immunohistochemical analyses were performed on liver and kidney tissues of rats. We determined Glutathione Peroxidase (GSH-Px), Superoxide Dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA), Nitric Oxide (NO) and Xanthine Oxidase (XO) levels in the liver and kidney. Moreover, Gamma Glutamyl Transferase (GGT), Direct Bilirubin (DBil), Blood Urea Nitrogen (BUN), and urea levels were measured in the serum. The histochemical evaluation revealed a significant decrease in MTX caused damage in the PTX- and ALA-treated groups (especially in ALA group). On the other hand, the immune staining of iNOS and TNF-α were observed most densely in the MTX group, while the density decreased in the PTX- and ALA-administered groups. We determined increased GGT, BUN, urea and levels of CAT, MDA, NO, and XO values in both groups, while GSH-Px (an increase in liver tissue) and DBil levels were decreased in the group that received MTX. However, we determined decreased SOD levels in liver tissue. In the PTX and ALA groups, the levels of GGT, BUN and urea as well as the levels of CAT, MDA, NO and XO decreased (SOD increased in the liver tissue), and the levels of GSH-Px and DBil increased. In conclusion, it can be stated that, although ALA is more effective in preventing the toxic effects of MTX on the liver and kidney, PTX also has a preventive effect. As a result, we can readily suggest that ALA and PTX can have protective effects by decreasing MDA, NO, BUN and urea values as antioxidants against MTX-induced damage in liver and kidney of rats.
Department of Histology and Embryology, School of Medicine, Süleyman Demirel University, Isparta, Turkey. Electronic address: ilkayarmagan@sdu.edu.tr.
Ilkay
I
Armagan
Department of Histology and Embryology, School of Medicine, Süleyman Demirel University, Isparta, Turkey.
Dilek
D
Bayram
Department of Histology and Embryology, School of Medicine, Süleyman Demirel University, Isparta, Turkey.
Ibrahim Aydin
IA
Candan
Department of Medical Genetics, School of Medicine, Süleyman Demirel University, Isparta, Turkey.
Ayse
A
Yigit
Biochemistry Division, Isparta State Hospital, Isparta, Turkey.
Erdal
E
Celik
Department of Emergency Medicine, School of Medicine, Süleyman Demirel University, Isparta, Turkey.
Hamit Hakan
HH
Armagan
Department of Biophysics, School of Medicine, Süleyman Demirel University, Isparta, Turkey.
Abdülhadi Cihangir
AC
Uğuz
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000008:administration & dosage* / Q000494:pharmacology
D000975:Antioxidants; D015415:Biomarkers; D008063:Thioctic Acid; D010431:Pentoxifylline; D008727:Methotrexate
Alpha lipoic acid; Kidney; Liver; Methotrexate; Oxidative stress; Pentoxifylline