Rutin attenuates oxidative damage-induced renal injury in rats experimentally infected with Cryptococcus neoformans by improving antioxidant capacity and reducing fungal burden

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis Pub Date : 2025-04-03 DOI:10.1016/j.micpath.2025.107540

Rafaela da Silva Rangel , Raquel Tusi Tamiosso , Rúbia Schallenberger da Silva , Laís Suarez da Silva de Oliveira , Maria Fernanda Biscarra Bortolotto Paz , Teodoro Trevisan De Paula Martins , Alice Mazaro , Alana Bianca de Moraes Chitolina , Marina Machado Maurente , Cinthia Melazzo de Andrade , Jandora Lima Ortiz , Isabela Maraschin Vieira , Marcelo Leite da Veiga , Matheus Dellaméa Baldissera

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引用次数: 0

Abstract

Oxidative stress plays a pivotal role in the pathophysiology of infectious diseases, contributing to pathogenesis and the appearance of clinical symptoms. However, the involvement of oxidative stress in renal cryptococcosis remains unknown, as do the potential protective effects of rutin. Cryptococcus neoformans is considered the main agent of cryptococcosis, a systemic life-threatening opportunistic fungal disease that affects internal organs. In 2022, the World Health Organization classified it as a critical-priority group on its Fungal Priority Pathogens List. Rutin, a flavonoid with potent antioxidant and antifungal properties, has been proposed as a protective agent. Thus, this study aimed to evaluate whether 50 mg rutin/kg body weight prevents or reduces C. neoformans var. grubii-induced renal oxidative stress. Renal fungal burden was significantly lower in rats that were treated with rutin and experimentally infected with C. neoformans, compared to those treated with saline solution and experimentally infected. Renal reactive oxygen species (ROS) and protein carbonylation levels were significantly higher in experimentally infected rats compared to uninfected controls, whereas catalase (CAT) and glutathione S-transferase (GST) activities were significantly lower. Treatment with rutin prevented the increase in renal ROS levels and the inhibition of CAT activity elicited by C. neoformans var. grubii. However, no significant differences were observed in lipid damage or superoxide dismutase activity. This study is the first to demonstrate that C. neoformans var. grubii infection induces renal oxidative damage in rats by promoting oxidative stress, increasing ROS levels, and impairing antioxidant defenses. Rutin treatment restored redox status in experimental rats through mechanisms involving oxidative stress. The protective effects of rutin against C. neoformans-induced kidney damage may result from its combined ability to scavenge ROS, inhibit protein damage, and enhance the antioxidant system.

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氧化应激在感染性疾病的病理生理学中起着关键作用，是发病机制和临床症状出现的诱因。然而，氧化应激在肾脏隐球菌病中的参与程度以及芦丁的潜在保护作用仍然未知。新型隐球菌被认为是隐球菌病的主要病原体，隐球菌病是一种影响内脏器官、危及生命的全身性机会真菌疾病。2022 年，世界卫生组织将其列为真菌性优先病原体名单中的关键优先群体。芦丁是一种具有强效抗氧化和抗真菌特性的类黄酮，被认为是一种保护剂。因此，本研究旨在评估 50 毫克芦丁/千克体重是否能预防或减轻 C. neoformans var.与接受生理盐水治疗和实验性感染的大鼠相比，接受芦丁治疗和实验性感染的大鼠的肾脏真菌负担明显降低。与未感染的对照组相比，实验感染大鼠的肾脏活性氧（ROS）和蛋白质羰基化水平明显升高，而过氧化氢酶（CAT）和谷胱甘肽 S-转移酶（GST）的活性则明显降低。用芦丁治疗可防止新酵母菌变种 grubii 引起的肾脏 ROS 水平升高和 CAT 活性受抑制。然而，在脂质损伤或超氧化物歧化酶活性方面没有观察到明显差异。这项研究首次证明，C. neoformans var. grubii感染会通过促进氧化应激、增加ROS水平和损害抗氧化防御功能来诱导大鼠肾脏氧化损伤。芦丁治疗可通过氧化应激机制恢复实验鼠的氧化还原状态。芦丁对新变形杆菌诱发的肾损伤具有保护作用，这可能是由于芦丁具有清除 ROS、抑制蛋白质损伤和增强抗氧化系统的综合能力。

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来源期刊

Microbial pathogenesis 医学-免疫学

CiteScore

7.40

自引率

2.60%

发文量

472

审稿时长

56 days

期刊介绍： Microbial Pathogenesis publishes original contributions and reviews about the molecular and cellular mechanisms of infectious diseases. It covers microbiology, host-pathogen interaction and immunology related to infectious agents, including bacteria, fungi, viruses and protozoa. It also accepts papers in the field of clinical microbiology, with the exception of case reports. Research Areas Include: -Pathogenesis -Virulence factors -Host susceptibility or resistance -Immune mechanisms -Identification, cloning and sequencing of relevant genes -Genetic studies -Viruses, prokaryotic organisms and protozoa -Microbiota -Systems biology related to infectious diseases -Targets for vaccine design (pre-clinical studies)