Ijaz Muhammad Umar, Ahmed Aqsa, Al-Ghanim Khalid Abdullah, Al-Misned Fahad, Riaz Mian Nadeem, Kaimkhani Zahid Ali, Mahboob Shahid
Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad 38040, Pakistan.
Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Toxics. 2023 Jan 24;11(2):110. doi: 10.3390/toxics11020110.
Arsenic (As) is a toxic contaminant present in organic and inorganic forms in the environment. Nobiletin (NOB) is a polymethoxy flavone that has recently gained substantial consideration due to its curative impacts. The present experiment was conducted to assess the hepatoprotective efficiency of NOB on As-generated hepatotoxicity. Twenty-four adult rats were equally distributed into four groups and designated as control, As (50 mg/kg)-treated, As + NOB (50 mg/kg and 25 mg/kg, respectively), and NOB (25 mg/kg)-treated groups. After 30 days, experimental animals were decapitated, then blood and tissue samples were collected for further analysis. The group treated with As showed a significant decrease in the activity of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione (GSH), glutathione reductase (GSR), and total antioxidant status (TAS), and a substantial increase in the accumulation of As in liver tissues, levels of total oxidant status (TOS), hydrogen peroxide (HO), and lipid peroxidation (TBARS). Significant increases in alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) levels were observed in As-treated rats. Moreover, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interleukin (IL)-6, and cyclo-oxygenase (COX)-2 activity, as well as the levels of pro-apoptotic markers (Bax, Caspase-3, and Caspase-9) were increased on exposure to As. In contrast, the anti-apoptotic marker (Bcl-2) level was significantly decreased. As administration showed a significant disturbance in hepatic tissue histology. However, cotreatment of NOB with As considerably increased the antioxidant enzyme activity, with a noteworthy reduction in the deposition of As in hepatic tissues, TBARS, and HO levels. NOB-administrated rats showed considerable recovery in terms of inflammation, apoptosis, and histological damage. Hence, NOB can be considered a useful curative compound due to its medicinal properties against As-prompted hepatotoxicity.
砷（As）是环境中以有机和无机形式存在的有毒污染物。川陈皮素（NOB）是一种多甲氧基黄酮，因其治疗作用最近受到了广泛关注。本实验旨在评估NOB对砷所致肝毒性的肝保护效果。将24只成年大鼠平均分为四组，分别命名为对照组、砷（50mg/kg）处理组、砷+NOB（分别为50mg/kg和25mg/kg）处理组和NOB（25mg/kg）处理组。30天后，将实验动物断头处死，然后采集血液和组织样本进行进一步分析。砷处理组的抗氧化酶活性显著降低，包括过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、过氧化物酶（POD）、谷胱甘肽（GSH）、谷胱甘肽还原酶（GSR）和总抗氧化状态（TAS），同时肝组织中砷的积累、总氧化状态（TOS）、过氧化氢（HO）和脂质过氧化（TBARS）水平显著升高。砷处理的大鼠中丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）和天冬氨酸转氨酶（AST）水平显著升高。此外，暴露于砷后，核因子（NF）-κB、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、白细胞介素（IL）-6和环氧化酶（COX）-2活性以及促凋亡标志物（Bax、Caspase-3和Caspase-9）水平均升高。相反，抗凋亡标志物（Bcl-2）水平显著降低。砷给药显示肝组织组织学有明显紊乱。然而，NOB与砷联合处理显著提高了抗氧化酶活性，肝组织中砷的沉积、TBARS和HO水平显著降低。给予NOB的大鼠在炎症、凋亡和组织学损伤方面有明显恢复。因此，由于NOB对砷诱导的肝毒性具有药用特性，可被认为是一种有用的治疗化合物。
