Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway
Protective Effect of Low Molecular Weight Peptides from Solenocera crassicornis Head against Cyclophosphamide-Induced Nephrotoxicity in Mice via the Keap1/Nrf2 Pathway
复制标题
巨角茄头低分子量肽通过 Keap1/Nrf2 途径对环磷酰胺诱导的小鼠肾毒性的保护作用
DOI：
10.3390/antiox9080745
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发表时间：
2020-08-01
期刊：
影响因子：
7
通讯作者：
Ding, Guofang
中科院分区：
文献类型：
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作者：
Jiang, Shuoqi;Zhang, Zhuangwei;Ding, Guofang
茄角虫粗角头蛋白水解物-组分1(SCHPS-F1)的主要成分是小分子多肽(MW<；1 kDa)。在这项研究中，我们研究了SCHPS-F1在环磷酰胺(CTX)中毒小鼠模型中潜在的肾脏保护作用。将40只雄性小鼠随机分为5组，分别给予生理盐水或80 mg/kg体重的环磷酰胺(CTX)，连续5天，然后分别给予生理盐水或SCHPS-F1(100,200,400 mg/kg体重)灌胃，连续15天。SCHPS-F1治疗可明显逆转CTX所致小鼠血尿素氮(BUN)、肌酐(Cre)和细胞色素P450(CyP450)水平的下降，并明显减轻肾组织学损害。此外，结果表明，SCHPS-F1可能通过减轻炎症反应、氧化应激和肾脏的细胞凋亡状态而减轻CTX所致的肾毒性，表现为降低丙二醛(MDA)、白介素1β(IL-1β)、白介素6(IL-6)、肿瘤坏死因子(TNF)-α和干扰素(干扰素)-γ的水平，提高总抗氧化能力(T-AOC)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)的水平。此外，SCHPS-F1还可抑制肾组织中促凋亡蛋白对B细胞淋巴瘤-2(Bcl2)相关的X(Bax)/Bcl2、半胱氨酸天冬氨酸特异性蛋白酶(Caspase)-3和caspase-9的过度表达。此外，在环磷酰胺所致的肾损伤模型中，SCHPS-F1还能刺激抗氧化因子核因子红系相关因子2(NRF2)的蛋白水平及其下游靶基因血红素加氧酶(HO-1)、谷氨酸半胱氨酸连接酶修饰亚基(GCLM)和NAD(P)H脱氢酶(QO-1)的表达。综上所述，我们的数据提示SCHPS-F1可能为减轻CTX引起的肾毒性提供一种新的潜在策略。
The major component of theSolenocera crassicornishead protein hydrolysates-fraction 1 (SCHPs-F1) are low molecular weight peptides (MW < 1 kDa). In this study, we investigated the potential renoprotective effects of SCHPs-F1 in a cyclophosphamide (CTX) toxicity mouse model. In brief, 40 male mice were randomly divided into 5 groups and received either saline or 80 mg/kg body weight (BW) CTX by intraperitoneal injection for 5 days, followed by either saline or SCHPs-F1 (100, 200, and 400 mg/kg BW) by intragastric administration for 15 days. SCHPs-F1 treatment significantly reversed the CTX-induced decreases in the levels of blood urea nitrogen (BUN), creatinine (CRE), and cytochrome P450 (CYP450), as well as the renal histological lesions. Furthermore, the results indicated that SCHPs-F1 potentially alleviated CTX-induced nephrotoxicity through mitigating inflammatory responses, oxidative stress, and apoptosis status of the kidneys, as evidenced by decreased levels of malondialdehyde (MDA), interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma and increased levels of total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, overexpression of pro-apoptotic proteins pair B-cell lymphoma-2 (Bcl-2)-associated X (Bax)/Bcl-2, cysteinyl aspartate specific proteinase (caspase)-3 and caspase-9 in renal tissues were suppressed by treatment with SCHPs-F1. In addition, the protein levels of the antioxidant factor nuclear factor erythroid-2 related factor 2 (Nrf2) and the expression levels of its downstream target genes heme-oxygenase (HO-1), glutamate-cysteine ligase modifier subunit (GCLM) and NAD(P)H dehydrogenase (quinone) 1 (NQO-1) were stimulated by treatment with SCHPs-F1 in the CTX-induced renal injury model. Taken together, our data suggested that SCHPs-F1 could provide a novel potential strategy in mitigating the nephrotoxicity caused by CTX.