Sakalli Çetin Esin, Tetiker Hasan, İlhan Çelik Özgür, Yılmaz Nigar, Ciğerci İbrahim Hakkı
Complement Med Res. 2017;24(6):364-370. doi: 10.1159/000468984. Epub 2017 May 4.
The protective effect of mistletoe extract (Helixor®, HLX) against methotrexate (MTX)-induced acute oxidative stress and nephrotoxicity in rats was evaluated by histological and biochemical methods as well as the comet assay.
32 female Wistar albino rats were divided into 4 groups: control group, HLX group (5 mg/kg body weight (bw), days 1-10, intraperitoneally (i.p.)), MTX group (10 mg/kg bw, days 7, 8, and 9, i.p.), and MTX + HLX group (10 mg/kg bw, days 7, 8, and 9, i.p. + 5 mg/kg bw, days 1-10, i.p.). At the end of the experiment, the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), nitric oxide (NO), and myeloperoxidase (MPO) levels were measured, and a histopathological analysis and comet assay were carried out.
MTX induced renal oxidative stress and nephrotoxicity in the rats. Pretreatment with HLX significantly improved the renal GSH-Px and SOD activities in the MTX + HLX group compared to the MTX group. The decrease in the NO and MPO levels in the rat groups pretreated with HLX was not significant. The histochemical evaluation revealed that HLX provided significant improvement in the MTX-induced renal degenerative changes, including tubule distension, interstitial inflammation, perirenal inflammation, glomerular congestion, glomerular degeneration, and parenchymal hemorrhage, in the MTX + HLX group compared to the MTX-administered group. According to the comet assay, pretreatment with HLX lowered the MTX-induced DNA damage in endogenous lymphocytes, although not significantly.
This study demonstrated that HLX administration markedly reduced the MTX-induced acute oxidative stress and nephrotoxicity in rats through its antioxidant and anti-inflammatory properties.
通过组织学、生物化学方法以及彗星试验评估了槲寄生提取物（Helixor®，HLX）对甲氨蝶呤（MTX）诱导的大鼠急性氧化应激和肾毒性的保护作用。
32只雌性Wistar白化大鼠分为4组：对照组、HLX组（5毫克/千克体重（bw），第1 - 10天，腹腔注射（i.p.））、MTX组（10毫克/千克bw，第7、8和9天，i.p.）以及MTX + HLX组（10毫克/千克bw，第7、8和9天，i.p. + 5毫克/千克bw，第1 - 10天，i.p.）。实验结束时，测量谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）、一氧化氮（NO）和髓过氧化物酶（MPO）水平，并进行组织病理学分析和彗星试验。
MTX诱导大鼠肾氧化应激和肾毒性。与MTX组相比，HLX预处理显著提高了MTX + HLX组大鼠肾GSH-Px和SOD活性。HLX预处理组大鼠中NO和MPO水平的降低不显著。组织化学评估显示，与MTX给药组相比，HLX使MTX + HLX组中MTX诱导的肾退行性变化得到显著改善，包括肾小管扩张、间质炎症、肾周炎症、肾小球充血、肾小球变性和实质出血。根据彗星试验，HLX预处理降低了MTX诱导的内源性淋巴细胞DNA损伤，尽管不显著。
本研究表明，HLX给药通过其抗氧化和抗炎特性显著降低了MTX诱导的大鼠急性氧化应激和肾毒性。
