Arshad Hadiqa, Doğan Muhammed Fatih, Zengin Münevver Nazlıcan, Özmen Özlem, Çiftçi Osman
Department of Pharmacology, Faculty of Medicine, Pamukkale University, Kinikli, Denizli, Turkey.
Department of Veterinary Pathology, Faculty of Veterinary Medicine, Mehmet Akif Ersoy University, Burdur, Turkey.
J Biochem Mol Toxicol. 2025 Aug;39(8):e70419. doi: 10.1002/jbt.70419.
This study aimed to demonstrate the protective effect of 1,8-cineole against Aroclor 1254 (A1254)-induced liver toxicity in male rats and to elucidate the underlying mechanisms. A1254 is among the persistent organic pollutants and is a toxic substance that can cause serious damage to various organs such as the liver, brain, and lungs. 1,8-cineole, a monoterpene, possesses significant pharmacological activities such as antioxidant, anti-inflammatory, and anticancer effects. Thirty-two healthy young (4-6 weeks) male Wistar albino rats (200-300 g) were used. The animals were randomly divided into four equal groups: Control, Aroclor, Cineole, and Aroclor+Cineole (n = 8). Rats were daily administered A1254 (1 mg/kg, intraperitoneally) either alone or in combination with 1,8-cineole (100 mg/kg orally in corn oil) for 30 days. The liver tissues and serum were collected from the rats under anesthesia. The protective effect of 1,8-cineole against A1254-induced liver damage was demonstrated using ELISA, RT-PCR, histopathological analysis, and immunohistochemical evaluation methods. A1254 administration increased the total oxidant status (TOS) level and triggered oxidative stress by decreasing the total antioxidant status (TAS). However, 1,8-cineole significantly reduced TOS levels and increased TAS levels in serum and liver tissues (p < 0.05). A1254 increased the pro-apoptotic Bax gene expression in liver tissues, while 1,8-cineole significantly decreased (p < 0.05). Similarly, A1254 increased the gene expressions of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1-beta (IL-1β), inducible nitric oxide synthase (iNOS), and interferon-gamma (INF-γ) in liver tissues, whereas 1,8-cineole decreased the expression of these genes (p < 0.05). Moreover, 1,8-cineole reduced the histopathological changes associated with A1254-induced oxidative stress and inflammation in liver tissues. In conclusion, 1,8-cineole may be a protective agent due to its anti-apoptotic effect, reduction of oxidative damage, anti-inflammatory efficacy, and amelioration of histopathological changes in liver toxicity.
本研究旨在证明1,8-桉叶素对雄性大鼠中Aroclor 1254（A1254）诱导的肝毒性的保护作用，并阐明其潜在机制。A1254属于持久性有机污染物，是一种能对肝脏、大脑和肺等各种器官造成严重损害的有毒物质。1,8-桉叶素是一种单萜，具有抗氧化、抗炎和抗癌等显著药理活性。使用了32只健康的年轻（4 - 6周）雄性Wistar白化大鼠（体重200 - 300克）。动物被随机分为四组，每组数量相等：对照组、Aroclor组、桉叶素组和Aroclor + 桉叶素组（n = 8）。大鼠每天单独或与1,8-桉叶素（100毫克/千克，溶于玉米油中口服）联合腹腔注射A1254（1毫克/千克），持续30天。在麻醉状态下从大鼠采集肝脏组织和血清。使用酶联免疫吸附测定（ELISA）、逆转录-聚合酶链反应（RT-PCR）、组织病理学分析和免疫组织化学评估方法证明了1,8-桉叶素对A1254诱导的肝损伤的保护作用。给予A1254会增加总氧化剂状态（TOS）水平，并通过降低总抗氧化剂状态（TAS）引发氧化应激。然而，1,8-桉叶素显著降低了血清和肝脏组织中的TOS水平，并提高了TAS水平（p < 0.05）。A1254增加了肝脏组织中促凋亡的Bax基因表达，而1,8-桉叶素显著降低了该表达（P < 0.05）。同样，A1254增加了肝脏组织中促炎细胞因子肿瘤坏死因子α（TNF-α）、白细胞介素-1β（IL-1β）、诱导型一氧化氮合酶（iNOS）和干扰素-γ（INF-γ）的基因表达，而1,8-桉叶素降低了这些基因的表达（p < 0.05）。此外，1,8-桉叶素减轻了与A1254诱导的肝脏组织氧化应激和炎症相关的组织病理学变化。总之，由于其抗凋亡作用、减少氧化损伤、抗炎功效以及改善肝毒性中的组织病理学变化，1,8-桉叶素可能是一种保护剂。
