Department of Histology and Embryology, School of Medicine, Süleyman Demirel University, Isparta, Turkey.
Department of Histology and Embryology, School of Medicine, Süleyman Demirel University, Isparta, Turkey.
Environ Toxicol Pharmacol. 2015 May;39(3):1122-31. doi: 10.1016/j.etap.2015.04.003. Epub 2015 Apr 13.
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.
本研究旨在探讨己酮可可碱（PTX）和硫辛酸（ALA）的可能保护作用，这两种药物具有抗氧化功效，可对抗甲氨蝶呤（MTX）的肝毒性和肾毒性，这是 MTX 的主要副作用。大鼠分为四组：对照组；MTX（20mg/kg/天）组；MTX+PTX（20mg/kg/天+50mg/kg/天）组；和 MTX+ALA（20mg/kg/天+100mg/kg/天）组。实验结束时，对大鼠肝、肾组织进行生化、组织化学和免疫组织化学分析。我们测定了肝、肾组织中的谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、丙二醛（MDA）、一氧化氮（NO）和黄嘌呤氧化酶（XO）水平。此外，还测定了血清中γ-谷氨酰转肽酶（GGT）、直接胆红素（DBil）、血尿素氮（BUN）和尿素水平。组织化学评价显示，PTX 和 ALA 处理组明显减轻了 MTX 引起的损伤（尤其是 ALA 组）。另一方面，iNOS 和 TNF-α 的免疫染色在 MTX 组中最为密集，而在 PTX 和 ALA 给药组中则减少。我们发现，两组 GGT、BUN、尿素和 CAT、MDA、NO、XO 值均升高，而 MTX 组 GSH-Px（肝组织升高）和 DBil 水平降低。然而，我们发现肝组织 SOD 水平降低。在 PTX 和 ALA 组中，GGT、BUN 和尿素水平以及 CAT、MDA、NO 和 XO 水平降低（肝组织 SOD 升高），GSH-Px 和 DBil 水平升高。综上所述，可以说，虽然 ALA 在预防 MTX 对肝、肾毒性方面更有效，但 PTX 也具有预防作用。因此，我们可以轻易地假设，ALA 和 PTX 通过降低 MDA、NO、BUN 和尿素值作为抗氧化剂，对 MTX 诱导的大鼠肝、肾损伤具有保护作用。
