Department of Medical Oncology, 64177Firat University Faculty of Medicine, Elazığ, Turkey.
Department of Internal Medicine, 64177Firat University Faculty of Medicine, Elazıg, Turkey.
Hum Exp Toxicol. 2020 Dec;39(12):1737-1746. doi: 10.1177/0960327120940365. Epub 2020 Jul 17.
Cutaneous side effects associated with sunitinib use are a major problem in patients receiving cancer treatment. The aim of this study was to investigate the protective effect of adenosine triphosphate (ATP) against possible skin damage resulting from sunitinib use in rats. Thirty Albino Winstar rats were divided into the following three groups: healthy controls (HCs, = 10), sunitinib (SUN, = 10), and sunitinib + ATP (SAT, = 10). ATP was injected intraperitoneally at a dose of 2 mg/kg. One hour subsequent to the administration of ATP and 0.9% NaCl, the SAT and SUN groups were orally administered a dose of 25 mg/kg sunitinib to the stomach. Macroscopic evaluation of the skin indicated lower levels of skin damage in the SAT group than in the SUN group. As an indicator of oxidative stress, malondialdehyde (MDA), total oxidant status (TOS), and oxidative stress index (OSI) levels were significantly higher in the SUN group than in the HC group, while total glutathione (tGSH) and total antioxidant status (TAS) levels were significantly lower. However, MDA, TOS, and OSI levels were significantly lower in the SAT group than in the SUN group, while tGSH and TAS levels were significantly higher. Histopathological examination revealed keratin plugs with edema, vasopathology, and inflammatory cell infiltration in the SUN group. The SAT group showed less necrotic epithelium, keratin plugs, edema, and vasopathology than the SUN group. ATP can be effective in preventing skin damage caused by sunitinib use by reducing oxidative stress.
舒尼替尼相关的皮肤副作用是接受癌症治疗患者的一个主要问题。本研究旨在探讨三磷酸腺苷(ATP)对舒尼替尼应用于大鼠后可能导致的皮肤损伤的保护作用。将 30 只白化 Winstar 大鼠分为以下三组:健康对照组(HCs,n = 10)、舒尼替尼组(SUN,n = 10)和舒尼替尼+ATP 组(SAT,n = 10)。ATP 以 2mg/kg 的剂量腹腔注射。在给予 ATP 和 0.9%生理盐水 1 小时后,SAT 和 SUN 组分别给予 25mg/kg 的舒尼替尼灌胃。皮肤的宏观评估表明,SAT 组的皮肤损伤程度低于 SUN 组。作为氧化应激的指标,丙二醛(MDA)、总氧化态(TOS)和氧化应激指数(OSI)水平在 SUN 组明显高于 HCs 组,而总谷胱甘肽(tGSH)和总抗氧化状态(TAS)水平明显降低。然而,SAT 组的 MDA、TOS 和 OSI 水平明显低于 SUN 组,而 tGSH 和 TAS 水平明显高于 SUN 组。组织病理学检查显示,SUN 组有角化栓、水肿、血管病变和炎症细胞浸润。与 SUN 组相比,SAT 组的坏死上皮、角化栓、水肿和血管病变更少。ATP 通过降低氧化应激,可有效预防舒尼替尼引起的皮肤损伤。