Eucalyptol regulates Nrf2 and NF-kB signaling and alleviates gentamicin-induced kidney injury in rats by downregulating oxidative stress, oxidative DNA damage, inflammation, and apoptosis.

IF 3.2 4区医学 Q1 Pharmacology, Toxicology and Pharmaceutics Toxicology Mechanisms and Methods Pub Date : 2024-05-01 Epub Date: 2023-12-26 DOI:10.1080/15376516.2023.2297234

Gokhan Akcakavak, Filiz Kazak, Ozhan Karatas, Halil Alakus, Ibrahim Alakus, Omer Kirgiz, Zeynep Celik, Mehmet Zeki Yilmaz Deveci, Ozgur Ozdemir, Mehmet Tuzcu

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Abstract

Gentamicin, an aminoglycoside antibiotic, is nowadays widely used in the treatment of gram-negative microorganisms. The antimicrobial, anti-inflammatory, and antioxidant activities of eucalyptol, a type of saturated monoterpene, have been reported in many studies. The aim of this study was to examine the possible effects of eucalyptol on gentamicin-induced renal toxicity. A total of 32 rats were divided into 4 groups; Control (C), Eucalyptol (EUC), Gentamicin (GEN), and Gentamicin + Eucalyptol (GEN + EUC). In order to induce renal toxicity, 100 mg/kg gentamicin was administered intraperitoneally (i.p.) for 10 consecutive days in the GEN and GEN + EUC groups. EUC and GEN + EUC groups were given 100 mg/kg orally of eucalyptol for 10 consecutive days. Afterwards, rats were euthanized and samples were taken and subjected to histopathological, biochemical, immunohistochemical, and real-time PCR examinations. The blood urea nitrogen (BUN) and creatinine (CRE) levels were significantly decreased in the GEN + EUC group (0.76 and 0.69-fold, respectively) compared to the GEN group. The glutathione peroxidase (GPx) and catalase (CAT) activities were significantly increased in the GEN + EUC group (1.35 and 2.67-fold, respectively) compared to the GEN group. In GEN group, Nuclear factor kappa B (NF-kB), Interleukin 1-beta (IL-1β), Inducible nitric oxide synthase (iNOS), Tumor necrosis factor-α (TNF-α), Caspase-3, 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and Nuclear factor erythroid 2-related factor (Nrf2) expression levels were found to be quite irregular. GEN + EUC group decreased the expressions of NF-kB, IL-1β, iNOS, TNF-α, Caspase-3, and 8-OHdG (0.55, 0.67, 0.54, 0.54, 0.63 and 0.67-fold, respectively), while it caused increased expression of Nrf2 (3.1 fold). In addition, eucalyptol treatment ameliorated the histopathological changes that occurred with gentamicin. The results of our study show that eucalyptol has anti-inflammatory, antioxidative, antiapoptotic, nephroprotective, and curative effects on gentamicin-induced nephrotoxicity.

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桉叶油醇通过下调氧化应激、氧化 DNA 损伤、炎症和细胞凋亡，调节 Nrf2 和 NF-kB 信号，减轻庆大霉素诱导的大鼠肾损伤。

庆大霉素是一种氨基糖苷类抗生素，如今被广泛用于治疗革兰氏阴性微生物。桉叶油醇是一种饱和单萜，其抗菌、消炎和抗氧化活性已被许多研究报道。本研究旨在探讨桉叶油醇对庆大霉素引起的肾毒性可能产生的影响。共有 32 只大鼠被分为 4 组：对照组（C）、桉叶油醇组（EUC）、庆大霉素组（GEN）和庆大霉素+桉叶油醇组（GEN + EUC）。为了诱发肾毒性，GEN 组和 GEN + EUC 组连续 10 天腹腔注射 100 毫克/千克庆大霉素。EUC组和GEN + EUC组连续10天口服100毫克/千克桉叶油醇。之后，对大鼠实施安乐死，并采集样本进行组织病理学、生物化学、免疫组织化学和实时 PCR 检测。与 GEN 组相比，GEN + EUC 组的血尿素氮（BUN）和肌酐（CRE）水平明显下降（分别为 0.76 倍和 0.69 倍）。与 GEN 组相比，GEN + EUC 组的谷胱甘肽过氧化物酶（GPx）和过氧化氢酶（CAT）活性明显提高（分别为 1.35 倍和 2.67 倍）。在 GEN 组中，核因子卡巴 B（NF-kB）、白细胞介素 1-β（IL-1β）、诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子-α（TNF-α）、Caspase-3、8-羟基-2'-脱氧鸟苷（8-OHdG）和核因子红细胞 2 相关因子（Nrf2）的表达水平相当不规则。GEN + EUC 组降低了 NF-kB、IL-1β、iNOS、TNF-α、Caspase-3 和 8-OHdG 的表达量（分别为 0.55、0.67、0.54、0.54、0.63 和 0.67 倍），而增加了 Nrf2 的表达量（3.1 倍）。此外，桉叶油醇还能改善庆大霉素引起的组织病理学变化。我们的研究结果表明，桉叶醇对庆大霉素诱导的肾毒性具有抗炎、抗氧化、抗凋亡、肾保护和治疗作用。

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来源期刊

Toxicology Mechanisms and Methods 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.