Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, 12622, Egypt.
Cardiovasc Toxicol. 2023 Jan;23(1):46-60. doi: 10.1007/s12012-022-09776-0. Epub 2023 Jan 17.
Cuprizone (CPZ) is a neurotoxic agent that is used to induce demyelination and neurotoxicity in rats. This study aimed to investigate the protective potential of sulforaphane (SF), nuclear factor E2 related factor (Nrf-2) activator, against CPZ-induced cardiotoxicity and hepatotoxicity. Male adult Wistar rats (n = 18) were fed with a regular diet or a CPZ-contained diet (0.2%) for four weeks. The rats were divided into three groups (n = 6): negative control rats, CPZ-exposed rats, and CPZ + SF treated rats. SF was intraperitoneally administrated (2 mg/kg/day) for two weeks. The anti-inflammatory and anti-oxidative functions of SF were investigated biochemically, histologically, and immunohistochemically. CPZ increased serum levels of cardiac troponin 1 (CTn1), aspartate amino transaminase (AST), alanine amino transaminase (ALT), and alkaline phosphatase (ALP). In addition, serum levels of inflammatory interferon-gamma (IFN-γ), and pro-inflammatory interleukin 1β (IL-1β) were significantly elevated. Moreover, CPZ administration provoked oxidative stress as manifested by declined serum levels of total antioxidant capacity (TAC), as well as, stimulated lipid peroxidation and decreased catalase activities in both cardiac and hepatic tissues. SF treatment reversed all these biochemical alterations through exerting anti-oxidative and anti-inflammatory activities, and this was supported by histopathological investigations in both cardiac and hepatic tissues. This SF-triggered modulation of oxidative stress and inflammation is strongly associated with Nrf-2 activation, as evidenced by activated immunoexpression in both cardiac and hepatic tissues. This highlights the cardioprotective and hepatoprotective activities of SF via Nrf-2 activation and enhancing catalase function.
杯铂（CPZ）是一种神经毒性剂，用于诱导大鼠脱髓鞘和神经毒性。本研究旨在探讨萝卜硫素（SF），核因子 E2 相关因子（Nrf-2）激活剂对 CPZ 诱导的心脏毒性和肝毒性的保护潜力。雄性成年 Wistar 大鼠（n = 18）喂食常规饮食或 CPZ 含量为 0.2%的饮食 4 周。将大鼠分为三组（n = 6）：阴性对照组大鼠、CPZ 暴露组大鼠和 CPZ + SF 治疗组大鼠。SF 经腹腔注射（2 mg/kg/天）2 周。通过生化、组织学和免疫组织化学研究 SF 的抗炎和抗氧化功能。CPZ 增加了血清中心肌肌钙蛋白 1（CTn1）、天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）和碱性磷酸酶（ALP）的水平。此外，血清中炎症性干扰素-γ（IFN-γ）和促炎白细胞介素 1β（IL-1β）的水平显著升高。此外，CPZ 给药引起氧化应激，表现为血清总抗氧化能力（TAC）水平下降，以及心脏和肝脏组织中的脂质过氧化和过氧化氢酶活性降低。SF 通过发挥抗氧化和抗炎作用逆转了所有这些生化变化，这在心脏和肝脏组织的组织病理学研究中得到了支持。SF 对氧化应激和炎症的这种调节作用与 Nrf-2 激活密切相关，这一点在心脏和肝脏组织中的免疫表达激活得到了证明。这突出了 SF 通过 Nrf-2 激活和增强过氧化氢酶功能对心脏和肝脏的保护作用。
