Secoisolariciresinol diglucoside mitigates benzo [a] pyrene-induced liver and kidney toxicity in mice via miR-101a/MKP-1-mediated p38 and ERK pathway
Secoisolariciresinol diglucoside mitigates benzo [a] pyrene-induced liver and kidney toxicity in mice via miR-101a/MKP-1-mediated p38 and ERK pathway
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DOI：
10.1016/j.fct.2021.112733
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发表时间：
2021-12-27
影响因子：
4.3
通讯作者：
Li, Dapeng
中科院分区：
文献类型：
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作者：
Ge, Junlin;Hao, Rili;Li, Dapeng
苯并[a]芘（BaP）可引起肝肾毒性。亚麻籽中的开环异落叶松树脂酚二葡萄糖苷（secoisolaricirestinoldiglucoside，SDG）具有抗氧化、抗炎、抗凋亡等多种生物活性。本研究旨在探讨SDG对苯并（a）芘（BaP）所致肝肾损伤的保护作用及其机制。40只雄性小鼠每天（通过胃管饲法; 4周）给予0.9%盐水（对照）、BaP（75 mg/kg体重（b.w.））、SDG（100 mg/kg体重），SDG（100 mg/kg体重）+ BaP（75 mg/kg体重）。结果表明，与BaP单用组相比，SDG + BaP组小鼠体重显著增加（P < 0.05），脏器重量比、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）活性显著降低（P <0.05），血清肌酐（CRE）和血尿素氮（BUN）水平显著降低（P < 0.05）。SDG给药减轻BaP诱导的氧化损伤、炎症和细胞凋亡。与BaP单独给药组相比，BaP能显著下调磷酸化蛋白激酶38（pp 38）和磷酸化细胞外调节蛋白激酶（p-ERK）水平，上调丝裂原活化蛋白激酶磷酸酶-1（MKP-1）水平，抑制miR-101 a表达（P < 0.05）。总而言之，这些结果首次表明SDG通过miR-101 a/MKP 1介导的p38和ERK途径调节氧化应激、炎症和细胞凋亡，对BaP诱导的小鼠肝肾毒性具有保护作用。
Benzo[a]pyrene (BaP) can cause hepatorenal toxicity. Secoisolariciresinol diglucoside (SDG), a polyphenolic compound present in flaxseed, has shown a variety of biological activities including antioxidant, anti-inflammatory, anti-apoptotic effects. This study aimed to investigate the protective effects and working mechanisms of SDG against BaP-induced hepatorenal injury. Forty male mice were administrated daily (via gastric gavage; 4 weeks) with 0.9% saline (control), BaP (75 mg/kg body weight (b.w.)), SDG (100 mg/kg b.w.), SDG (100 mg/kg b.w.)+BaP (75 mg/kg b.w.). Results showed that the mice treated with SDG + BaP had significantly (P < 0.05) higher body weight, lower organ-to-body weight ratio, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) activities, and less levels of serum creatinine (CRE) and blood urea nitrogen (BUN) than those treated with BaP alone. SDG administration alleviated BaP-induced oxidative damages, inflammation and apoptosis. Furthermore, it significantly (P < 0.05) downregulated phosphor-p-38 (pp38) and phosphor-extracellular regulated protein kinases (p-ERK) levels, upregulated mitogen-activated protein kinase phosphatase-1 (MKP-1) level, and suppressed miR-101a expression compared with BaP alone group. Taken together, these results showed for the first time that SDG has protective effects against BaP-induced liver and kidney toxicity in mice through regulating oxidative stress, inflammation and apoptosis via miR-101a/MKP1-mediated p38 and ERK pathway.