Benayad Salma, Es-Sai Basma, Laaziouez Yassir, Rabbaa Soufiane, Wahnou Hicham, Bouchab Habiba, El Attar Hicham, Benabdelkhalek Bouchra, Amahdar Loubna, Abboussi Oualid, Duval Raphaël Emmanuel, El Kebbaj Riad, Limami Youness
Sciences and Engineering of Biomedicals, Biophysics and Health Laboratory, Higher Institute of Health Sciences, Hassan First University, Settat 26000, Morocco.
Laboratory of Integrative Biology, Faculty of Sciences Ain Chock, Hassan II University, B.P 2693, Maarif, Casablanca 20100, Morocco.
Molecules. 2025 Aug 1;30(15):3231. doi: 10.3390/molecules30153231.
Barium chloride (BaCl), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination.
氯化钡（BaCl）是一种已知的环境污染物，它通过破坏氧化还原稳态诱导器官特异性氧化应激。本研究采用两阶段实验方案，评估了叶绿酸铜钠（SCC）和抗坏血酸（ASC）对BaCl诱导的小鼠肝脏和脑氧化损伤的保护作用及安全性。在暴露于BaCl（饮用水中150 mg/L，持续7天）之前，动物接受SCC（40 mg/kg）、ASC（160 mg/kg）或它们的组合，为期14天，以便评估预防和治疗效果。毒理学和行为学评估证实，补充后不存在全身毒性或神经行为改变。体重、肝脏和肾脏指数以及生化标志物（天冬氨酸转氨酶（ASAT）、丙氨酸转氨酶（ALAT）、肌酐）保持在生理范围内，未观察到焦虑或运动效应。在脑中，与对照组相比，BaCl暴露显著增加了超氧化物歧化酶（SOD）（+49%）、过氧化氢酶（CAT）（+66%）、谷胱甘肽过氧化物酶（GPx）（+24%）和谷胱甘肽（GSH）（+26%），反映出强大的代偿性抗氧化反应。尽管脂质过氧化（MDA）显示出非显著性增加，但SCC、ASC及其组合分别使MDA水平降低了42%、37%和55%。这些处理使抗氧化酶活性和GSH恢复正常，表明具有有效的神经保护作用。相比之下，肝脏表现出不同的氧化特征。BaCl暴露使MDA水平增加了80%，GSH增加了34%，SOD、CAT或GPx未被激活。组织学分析显示广泛的肝细胞坏死、空泡化和炎症浸润。SCC使肝脏MDA显著降低39%，并保留了组织结构，而单独使用ASC或与SCC联合使用时，相对于BaCl暴露的对照组分别使炎症加剧，肝脏GSH耗竭71%和78%。总体而言，这些结果突出了对BaCl诱导的氧化应激的差异、器官特异性反应以及SCC和ASC的治疗潜力。SCC是一种更安全、更有效的药物，特别是在肝脏保护方面，而两种抗氧化剂单独使用或联合使用时均表现出神经保护作用。
