Spherical Carbon Adsorbent (AST-120) Protects Deterioration of Renal Function in Chronic Kidney Disease Rats through Inhibition of Reactive Oxygen Species Production from Mitochondria and Reduction of Serum Lipid Peroxidation

Abstract

Background/Aim: An imbalance in renal redox status contributes to progression of renal dysfunction. We investigated the effects of an oral charcoal adsorbent (AST-120) on renal redox status, superoxide production from renal mitochondria, and serum lipid peroxidation using chronic kidney disease (CKD) model rats. Methods: CKD was induced by 5/6 nephrectomy. CKD rats were divided into 2 groups: controls, and those treated with AST-120 for 20 weeks. We evaluated: (1) renal redox status by in vivo low-frequency electron spin resonance imaging (EPRI); (2) renal superoxide scavenging activity (SSA); (3) superoxide production from renal mitochondria; (4) immunostaining for Cu-Zn superoxide dismutase (SOD), and (5) oxidative stress markers including LDL-negative charge (LDL-CMF), serum lipid peroxide (LPO) and urinary hexanoyl-lysine (HEL). The effect of indoxyl sulfate, a uremic toxin, on mitochondrial superoxide production was also investigated. Results: AST-120 treatment improved renal function, renal SSA, renal mitochondrial superoxide production, renal SOD expression, renal redox status by EPRI, and oxidative stress profiles by LDL-CMF, LPO and urinary HEL. Addition of indoxyl sulfate increased mitochondrial superoxide production and AST-120 also decreased this. Conclusions: Improvements in the redox status and lipid peroxidation induced by AST-120 may delay the progression of CKD.

Effects of AST-120 on Blood Concentrations of Protein-Bound Uremic Toxins and Biomarkers of Cardiovascular Risk in Chronic Dialysis Patients

“…Furthermore, oxidative stress is one of the major mechanisms responsible for the toxic effects of protein-bound uremic toxins [7,15]. Therapy with AST-120 in both clinical and animal studies can suppress oxidative stress in renal failure [23,32]. Our study for the first time presents that AST-120 can decrease the MDA level in dialysis patients.…”

The Kidney and Uremic Toxin Removal: Glomerulus or Tubule?

“…104 Indoleacetic acid in particular had a pronounced negative impact on 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide reduction, and high-resolution respirometry showed that this solute diminished the maximum capacity of the electron transport system, signifying a reduction in the reserve capacity of the oxidative phosphorylation system. 104 In addition, Owada et al 105 showed that indoxyl sulfate increased the production of superoxide and hydroxyl radicals in rat kidney mitochondria, and Dzurik et al 106 reported that hippuric acid reduced ammonia production by P-dependent mitochondrial glutaminase in kidney homogenates from rats, thereby shifting ammonia production from mitochondria to the lumen of proximal tubules. In addition, reduced functioning of hepatic mitochondria after exposure to dialysate and p-cresol have been reported previously.…”

Oral activated charcoal suppresses hyperphosphataemia in haemodialysis patients

“…In addition, oAC has extensive effects on immune and inflammatory processes. It can absorb endotoxin‐induced cytokines and reduce the production of tumour necrosis factor (TNF) and interferon c (IFNc), 20 it was proved to improve renal function 22 …”