The prophylactic and therapeutic effects of cannabidiol on lung injury secondary to cardiac ischemia model in rats via PERK/NRF2/CHOP/BCL2 pathway.

IF 2.9 4区 医学 Q3 IMMUNOLOGY Immunopharmacology and Immunotoxicology Pub Date : 2024-10-01 Epub Date: 2024-07-29 DOI:10.1080/08923973.2024.2384904
Ozlem Ozmen, Halil Asci, Dincer Uysal, Ilter Ilhan, Rumeysa Taner, Melih Arlıoglu, Adem Milletsever, Serife Tasan
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Abstract

Background: Inflammation and oxidative stress are key players in lung injury stemming from cardiac ischemia (LISCI). Cannabidiol (CBD) demonstrates tissue-protective properties through its antioxidant, anti-inflammatory, and anti-apoptotic characteristics. This study aims to assess the preventive (p-CBD) and therapeutic (t-CBD) effects of CBD on LISCI.

Methods: Forty male Wistar Albino rats were divided into four groups: control (CON), LISCI, p-CBD, and t-CBD. The left anterior descending coronary artery was ligated for 30 min of ischemia followed by 30 min of reperfusion. Lung tissues were then extracted for histopathological, immunohistochemical, genetic, and biochemical analyses.

Results: Histopathologically, marked hyperemia, increased septal tissue thickness, and inflammatory cell infiltrations were observed in the lung tissues of the LISCI group. Spectrophotometrically, total oxidant status and oxidative stress index levels were elevated, while total antioxidant status levels were decreased. Immunohistochemically, expressions of cyclooxygenase-1 (COX1), granulocyte colony-stimulating factor (GCSF), interleukin-6 (IL6) were increased. In genetic analyses, PERK and CHOP expressions were increased, whereas Nuclear factor erythroid 2-related factor 2 (NRF2) and B-cell leukemia/lymphoma 2 protein (BCL2) expressions were decreased. These parameters were alleviated by both prophylactic and therapeutic CBD treatment protocols.

Conclusion: In LISCI-induced damage, both endoplasmic reticulum and mitochondrial stress, along with oxidative and inflammatory markers, were triggered, resulting in lung cell damage. However, both p-CBD and t-CBD treatments effectively reversed these mechanisms, normalizing all histopathological, biochemical, and PCR parameters.

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大麻二酚通过 PERK/NRF2/CHOP/BCL2 通路对心脏缺血模型大鼠肺损伤的预防和治疗作用
背景:炎症和氧化应激是心脏缺血导致肺损伤(LISCI)的关键因素。大麻二酚(CBD)具有抗氧化、抗炎和抗细胞凋亡的特性,因而具有保护组织的作用。本研究旨在评估大麻二酚对 LISCI 的预防(p-CBD)和治疗(t-CBD)作用:方法:将 40 只雄性 Wistar Albino 大鼠分为四组:对照组(CON)、LISCI 组、p-CBD 组和 t-CBD 组。结扎左前降支冠状动脉,缺血 30 分钟,然后再灌注 30 分钟。然后提取肺组织进行组织病理学、免疫组化、遗传和生化分析:从组织病理学角度看,LISCI 组的肺组织中出现了明显的充血、间隔组织厚度增加和炎性细胞浸润。分光光度法显示,总氧化状态和氧化应激指数水平升高,而总抗氧化状态水平下降。免疫组化方面,环氧化酶-1(COX1)、粒细胞集落刺激因子(GCSF)和白细胞介素-6(IL6)的表达均有所增加。在基因分析中,PERK 和 CHOP 表达增加,而核因子红细胞 2 相关因子 2(NRF2)和 B 细胞白血病/淋巴瘤 2 蛋白(BCL2)表达减少。这些参数在预防性和治疗性 CBD 治疗方案中都得到了缓解:结论:在LISCI诱导的损伤中,内质网和线粒体应激以及氧化和炎症标志物都被触发,导致肺细胞损伤。然而,p-CBD 和 t-CBD 治疗都能有效逆转这些机制,使所有组织病理学、生化和 PCR 参数恢复正常。
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来源期刊
CiteScore
5.40
自引率
0.00%
发文量
133
审稿时长
4-8 weeks
期刊介绍: The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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