Muthuraman Arunachalam, Sayem Abu Sadat Md, Meenakshisundaram Sakthiganapathi, Ali Nemat, Ahmad Sheikh F, AlAsmari Abdullah F, Nishat Shamama, Lim Khian Giap, Paramaswaran Yamunna
Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, Bedong 08100, Kedah, Malaysia.
School of Pharmacy, Sri Balaji Vidyapeeth, Pillaiyarkuppam, Pondicherry 607402, India.
Biomedicines. 2023 Sep 27;11(10):2654. doi: 10.3390/biomedicines11102654.
Indoxyl sulfate (IS) is a metabolic byproduct of indole metabolism. IS readily interacts with the mitochondrial redox metabolism, leading to altered renal function. The β-carotene oxygenase-2 (BCO2) enzyme converts carotenoids to intermediate products. However, the role of β-carotene (BC) in IS-induced renal dysfunction in zebrafish and their modulatory action on BCO2 and mitochondrial inflammations have not been explored yet. Hence, the present study is designed to investigate the role of BC in the attenuation of IS-induced renal dysfunction via regulations of mitochondrial redox balance by BCO2 actions. Renal dysfunction was induced by exposure to IS (10 mg/L/hour/day) for 4 weeks. BC (50 and 100 mg/L/hour/day) and coenzyme Q10 (CoQ10; 20 mg/L/hour/day) were added before IS exposure. BC attenuated the IS-induced increase in blood urea nitrogen (BUN) and creatinine concentrations, adenosine triphosphate (ATP), and complex I activity levels, and the reduction of renal mitochondrial biomarkers, i.e., BCO2, superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (GPX1), reduced and oxidized glutathione (GSH/GSSG) ratio, and carbonylated proteins. Moreover, renal histopathological changes were analyzed by the eosin and hematoxylin staining method. As a result, the administration of BC attenuated the IS-induced renal damage via the regulation of mitochondrial function.
硫酸吲哚酚（IS）是吲哚代谢的一种代谢副产物。IS很容易与线粒体氧化还原代谢相互作用，导致肾功能改变。β-胡萝卜素加氧酶-2（BCO2）可将类胡萝卜素转化为中间产物。然而，β-胡萝卜素（BC）在斑马鱼IS诱导的肾功能障碍中的作用及其对BCO2和线粒体炎症的调节作用尚未得到研究。因此，本研究旨在通过BCO2作用调节线粒体氧化还原平衡，探讨BC在减轻IS诱导的肾功能障碍中的作用。通过暴露于IS（10 mg/L/小时/天）4周诱导肾功能障碍。在暴露于IS之前添加BC（50和100 mg/L/小时/天）和辅酶Q10（CoQ10；20 mg/L/小时/天）。BC减轻了IS诱导的血尿素氮（BUN）和肌酐浓度、三磷酸腺苷（ATP）以及复合体I活性水平的升高，以及肾线粒体生物标志物的降低，即BCO2、超氧化物歧化酶-2（SOD2）、谷胱甘肽过氧化物酶-1（GPX1）、还原型和氧化型谷胱甘肽（GSH/GSSG）比值以及羰基化蛋白。此外，通过伊红和苏木精染色法分析肾脏组织病理学变化。结果，BC的给药通过调节线粒体功能减轻了IS诱导的肾损伤。
