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Oral adsorbent AST-120 ameliorates gut environment and protects against the progression of renal impairment in CKD rats
- Source :
- Clinical and Experimental Nephrology
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Background Oral charcoal adsorbent AST-120 (AST) is reported to ameliorate renal dysfunction by the absorption of toxic substance in the gut. Recent study revealed that, in CKD, gut environment is disturbed including the decrease in tight junctions and Lactobacillus (Lact). In this study, we examined whether AST improves the renal dysfunction through gut environment. Method Six-week-old spontaneously hypertensive rats (SHR) were rendered CKD by 5/6th nephrectomy (Nx). SHRs were divided into SHR (Sham), SHR with Nx (Nx), and Nx given AST (Nx + AST) (n = 10, each). After 12 weeks, rats were killed and biochemical parameters were explored. The gut flora was analyzed. Furthermore, gut molecular changes in tight junctions and toll-like receptors were examined. We also investigated the effects of the combination therapy with AST and Lact. Results The increase in serum urea nitrogen and urinary protein excretion in Nx was restored in Nx + AST. The increased renal glomerulosclerosis in Nx was ameliorated in Nx + AST. Increases in serum uremic toxins and IL-6 in Nx were ameliorated in Nx + AST. The gut flora analysis revealed that the decrease in Lact in Nx was restored in Nx + AST. The downregulation in the tight junction and TLR2 in Nx was mitigated by AST. However, combination therapy failed to exhibit additional effects. Conclusion AST ameliorated renal function with the restoration of Lact and tight junction through TLR pathway, which would mitigate systemic inflammation and contributed to their renoprotective effects. Our study provides a novel mechanism of the renoprotective effects by AST.
- Subjects :
- 0301 basic medicine
Nephrology
medicine.medical_specialty
Physiology
030232 urology & nephrology
Renal function
Gut flora
Systemic inflammation
Nephrectomy
digestive system
Excretion
03 medical and health sciences
fluids and secretions
0302 clinical medicine
Toll-like receptor
Rats, Inbred SHR
Physiology (medical)
Internal medicine
CKD
polycyclic compounds
Animals
Medicine
Renal Insufficiency, Chronic
Tokyo
Tight junction
biology
business.industry
Microbiota
virus diseases
Glomerulosclerosis
Oxides
medicine.disease
biology.organism_classification
Carbon
digestive system diseases
Rats
TLR2
030104 developmental biology
Endocrinology
Intestinal Absorption
Uremic toxin
Original Article
medicine.symptom
business
Subjects
Details
- ISSN :
- 14377799 and 13421751
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Clinical and Experimental Nephrology
- Accession number :
- edsair.doi.dedup.....2762f71d15481027dea87c253f9e1246
- Full Text :
- https://doi.org/10.1007/s10157-018-1577-z