Lycopene alleviates zearalenone-induced oxidative stress, apoptosis, and NLRP3 inflammasome activation in mice kidneys

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
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Abstract

The aim of this study was to investigate the protective effects of lycopene on renal damage caused by zearalenone (ZEN). Male Kunming mice were treated daily for 4 weeks by intragastric administration with 40 mg/kg ZEN in the presence or absence of lycopene (2.5 or 5 mg/kg). The results showed that lycopene markedly alleviated the damage of renal structure and function in mice induced by ZEN, as indicated by the reduced degree of pathological damage and the decreased levels of urea nitrogen and creatinine. Meanwhile, results of dihydroethidine (DHE) staining and biochemical markers revealed that ZEN exposure notably increased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), decreased the level of GSH, and reduced the activities of catalase (CAT) and superoxide dismutase (SOD). Administration of lycopene alleviated the increased oxidative stress induced by ZEN. Moreover, ZEN ingestion notably resulted in apoptosis, increased the protein levels of BCL2 associated X protein (Bax) and cleaved caspase-3, and decreased the protein levels of apoptosis regulator Bcl-2 (Bcl-2), which were reversed by lycopene intervention. Results of immunofluorescence demonstrated that lycopene reversed ZEN-induced the upregulation of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), Caspase-1, and interleukin-1 beta (IL-1β) in mice kidneys. Lycopene supplementation could alleviate ZEN-induced renal toxicity by inhibiting oxidative stress, apoptosis, and NLRP3 inflammasome activation.

Abstract Image

番茄红素可减轻玉米赤霉烯酮诱导的小鼠肾脏氧化应激、细胞凋亡和 NLRP3 炎性体激活。
本研究旨在探讨番茄红素对玉米赤霉烯酮(ZEN)引起的肾损伤的保护作用。雄性昆明小鼠在番茄红素(2.5 或 5 毫克/千克)存在或不存在的情况下,每天胃内注射 40 毫克/千克玉米赤霉烯酮,连续治疗 4 周。结果表明,番茄红素明显减轻了 ZEN 对小鼠肾脏结构和功能的损伤,表现为病理损伤程度减轻,尿素氮和肌酐水平降低。同时,双氢乙脒(DHE)染色和生化指标结果显示,ZEN 暴露显著增加了活性氧(ROS)和丙二醛(MDA)的水平,降低了 GSH 的水平,降低了过氧化氢酶(CAT)和超氧化物歧化酶(SOD)的活性。番茄红素能缓解 ZEN 引起的氧化应激增加。此外,摄入 ZEN 会显著导致细胞凋亡,增加 BCL2 相关 X 蛋白(Bax)和裂解的 Caspase-3 的蛋白水平,降低凋亡调节因子 Bcl-2 (Bcl-2)的蛋白水平。免疫荧光结果表明,番茄红素可逆转 ZEN 诱导的小鼠肾脏中 NOD 样受体 pyrin 结构域含蛋白 3(NLRP3)、Caspase-1 和白细胞介素-1β(IL-1β)的上调。补充番茄红素可抑制氧化应激、细胞凋亡和 NLRP3 炎性体的激活,从而减轻 ZEN 引起的肾毒性。
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来源期刊
Toxicon
Toxicon 医学-毒理学
CiteScore
4.80
自引率
10.70%
发文量
358
审稿时长
68 days
期刊介绍: Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee. Toxicon''s "aims and scope" are to publish: -articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms -papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins -molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins -clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained. -material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems. -articles on the translational application of toxins, for example as drugs and insecticides -epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged. -articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon. -review articles on problems related to toxinology. To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.
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