Department of Medical Pharmacology, School of Medicine, Mustafa Kemal University, Hatay, Turkey.
Department of Medical Pharmacology, School of Medicine, Cukurova University, Adana, Turkey.
Biomed Pharmacother. 2018 Jun;102:758-764. doi: 10.1016/j.biopha.2018.03.147. Epub 2018 Apr 5.
Methotrexate (MTX) is used in the treatment of certain types of cancers and chronic inflammatory illnesses, although the clinical use of MTX is limited due to its adverse effects, the most common of which are hepatotoxicity and nephrotoxicity. In the present study, we demonstrate the protecting influence of tempol related to oxidative stress in MTX-induced liver toxicity in rats using histopathological and biochemical parameters. The rats were divided into four groups: control group (group 1), tempol group (group 2), MTX group (group 3) and MTX + tempol group (group 4). The control group (group 1) received physiological saline for 10 days; the tempol group (group 2) received 30 mg/kg i.p. for 10 days, the MTX group (group 3) received a single dose of 20 mg/kg intraperitoneal (i.p.) on the fourth day of the study, and the MTX + tempol group (group 4) received a single dose of 20 mg/kg i.p. on the fourth day, followed by tempol 30 mg/kg i.p. for 10 days. Malondialdehyde (MDA), myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were found to be significantly lower in the MTX + tempol group then in the MTX group; while superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were found to be higher in the MTX + tempol group than in the MTX group. Tempol ameliorates vacuolic degeneration, inflammation and necrosis in MTX-treated rats. Our study demonstrates that tempol treatment after MTX administration ameliorates oxidative damage in liver tissue in rats.
甲氨蝶呤（MTX）用于治疗某些类型的癌症和慢性炎症性疾病，尽管由于其副作用，MTX 的临床应用受到限制，最常见的是肝毒性和肾毒性。在本研究中，我们使用组织病理学和生化参数证明了在 MTX 诱导的大鼠肝毒性中，tempo 与氧化应激相关的保护作用。将大鼠分为四组：对照组（第 1 组）、tempo 组（第 2 组）、MTX 组（第 3 组）和 MTX+tempo 组（第 4 组）。对照组（第 1 组）连续 10 天接受生理盐水；tempo 组（第 2 组）连续 10 天接受 30mg/kg 腹腔注射；MTX 组（第 3 组）在研究的第 4 天接受单次 20mg/kg 腹腔注射，MTX+tempo 组（第 4 组）在第 4 天接受单次 20mg/kg 腹腔注射，随后连续 10 天接受 30mg/kg 腹腔注射。MTX+tempo 组的丙二醛（MDA）、髓过氧化物酶（MPO）、天门冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）水平明显低于 MTX 组；而超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）水平在 MTX+tempo 组中高于 MTX 组。tempo 改善了 MTX 治疗大鼠的空泡变性、炎症和坏死。我们的研究表明，MTX 给药后 tempo 治疗可改善大鼠肝组织的氧化损伤。
