College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin 150030, China.
College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, 59 Mucai Street, Harbin 150030, China.
J Nutr Biochem. 2018 Feb;52:115-123. doi: 10.1016/j.jnutbio.2017.09.025. Epub 2017 Oct 12.
Lead-induced hepatotoxicity is characterized by an extensive oxidative stress. Grape seed procyanidin extract (GSPE) possesses abundant biological activities. Herein, we investigated the protective role of GSPE against lead-induced liver injury and determined the potential molecular mechanisms. In vivo, rats were treated with/without lead acetate (PbAc) (0.05%, w/v) in the presence/absence of GSPE (200 mg/kg). In vitro, hepatocytes were pretreated with/without GSPE (100 μg/ml) in the presence/absence of PbAc (100 μM). PbAc administration to rats resulted in anemia, liver dysfunction, lead accumulation in the bone and liver, oxidative stress, DNA damage and apoptosis. GSPE significantly attenuated these adverse effects, except lead accumulation in liver. GSPE also decreased the expression of miRNA153 and increased the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and levels of its downstream protein, and protein kinase B (AKT) phosphorylation in PbAc-induced liver injury. In primary hepatocytes treated with PbAc, GSPE increased hepatocyte viability and decreased lactate dehydrogenase release and reactive oxygen species levels. Dietary GSPE attenuated PbAc-induced liver injury in rats via an integrated mechanism associated with the miRNA153 and AKT/glycogen synthase kinase 3 beta/Fyn-mediated Nrf2 activation.
铅诱导的肝毒性的特征是广泛的氧化应激。葡萄籽原花青素提取物（GSPE）具有丰富的生物活性。在此，我们研究了 GSPE 对铅诱导的肝损伤的保护作用，并确定了其潜在的分子机制。在体内，大鼠用/不用醋酸铅（PbAc）（0.05%，w/v）处理，同时用/不用 GSPE（200mg/kg）处理。在体外，用/不用 GSPE（100μg/ml）预处理肝细胞，同时用/不用 PbAc（100μM）处理。PbAc 给药导致大鼠贫血、肝功能障碍、骨和肝中铅积累、氧化应激、DNA 损伤和细胞凋亡。GSPE 显著减轻了这些不良反应，除了肝中铅的积累。GSPE 还降低了 miRNA153 的表达，增加了核因子红细胞 2 相关因子 2（Nrf2）的核易位及其下游蛋白、蛋白激酶 B（AKT）磷酸化水平，在 PbAc 诱导的肝损伤中。在 PbAc 处理的原代肝细胞中，GSPE 增加了肝细胞活力，降低了乳酸脱氢酶释放和活性氧水平。膳食 GSPE 通过与 miRNA153 和 AKT/糖原合成酶激酶 3β/Fyn 介导的 Nrf2 激活相关的综合机制减轻了大鼠的 PbAc 诱导的肝损伤。
