Preventive Action of Beta-Carotene against the Indoxyl Sulfate-Induced Renal Dysfunction in Male Adult Zebrafish via Regulations of Mitochondrial Inflammatory and β-Carotene Oxygenase-2 Actions.

Abstract

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.