Ahmed Amal A M, Selim Manar A A, El-Sayed Norhan M
Department of Cytology & Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.
Department of Oral biology, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt.
Life Sci. 2017 Feb 15;171:51-59. doi: 10.1016/j.lfs.2017.01.001. Epub 2017 Jan 3.
Oral mucositis is a common adverse effect of Methotrexate (MTX) that may limit its clinical use. Oxidative stress and apoptosis have been proposed to mediate MTX toxicity. The current study was conducted to assess the conceivable protective effect of α-lipoic acid (LA) against MTX induced toxicity on both buccal and lingual mucosae.
Thirty male Wistar rats were allocated into three groups; control, MTX-treated group subjected to single intraperitoneal injection of MTX (20mg/kg, i.p.) and LA- treated group treated with daily intraperitoneal injection of LA (10mg/kg, i.p.) for 5weeks before MTX injection (20mg/kg, i.p.). Rats were then sacrificed under anesthesia then their buccal and lingual mucosae were dissected out and processed for biochemical and histopathological studies. Biomarkers of oxidative stress and integrity of nuclear DNA (nDNA) were estimated. Immunostaining was used to determine Bax and PCNA localization.
MTX-treated rats showed increased levels of MDA and fragmentation of DNA in addition to reduction of GSH levels and activities of catalase and SOD. Histological examination of MTX-treated rats demonstrated degenerative changes that involved the surface epithelium and lamina propria of their buccal and lingual mucosae. Immunohistochemical results of MTX-treated rats revealed strongly positive Bax and weakly positive PCNA staining reactivity of the nuclei of the basal and parabasal cells of the surface epithelium. However, LA significantly attenuated MTX-evoked alterations in the previous-stated parameters highlighting its antioxidant and anti-apoptotic potential.
LA may be suggested to be a prospective candidate to ameliorate MTX-induced oral mucositis.
口腔黏膜炎是甲氨蝶呤（MTX）常见的不良反应，可能会限制其临床应用。氧化应激和细胞凋亡被认为介导了MTX的毒性作用。本研究旨在评估α-硫辛酸（LA）对MTX诱导的颊黏膜和舌黏膜毒性可能具有的保护作用。
将30只雄性Wistar大鼠分为三组；对照组、单次腹腔注射MTX（20mg/kg，腹腔注射）的MTX治疗组和在注射MTX（20mg/kg，腹腔注射）前5周每日腹腔注射LA（10mg/kg，腹腔注射）的LA治疗组。然后在麻醉下处死大鼠，取出其颊黏膜和舌黏膜，进行生化和组织病理学研究。评估氧化应激生物标志物和核DNA（nDNA）的完整性。采用免疫染色法确定Bax和PCNA的定位。
MTX治疗的大鼠除了谷胱甘肽（GSH）水平降低以及过氧化氢酶和超氧化物歧化酶（SOD）活性降低外，还表现出丙二醛（MDA）水平升高和DNA片段化。MTX治疗大鼠的组织学检查显示其颊黏膜和舌黏膜的表面上皮和固有层出现退行性变化。MTX治疗大鼠的免疫组织化学结果显示，表面上皮基底细胞和副基底细胞核的Bax染色反应呈强阳性，PCNA染色反应呈弱阳性。然而，LA显著减轻了MTX引起的上述参数变化，突出了其抗氧化和抗凋亡潜力。
LA可能是改善MTX诱导的口腔黏膜炎的潜在候选药物。
