TY - JOUR
T1 - Antioxidant and renoprotective activity of 2-hydroxypropyl-β-cyclodextrin in nephrectomized rats
AU - Anraku, Makoto
AU - Iohara, Daisuke
AU - Wada, Koki
AU - Taguchi, Kazuaki
AU - Maruyama, Toru
AU - Otagiri, Masaki
AU - Uekama, Kaneto
AU - Hirayama, Fumitoshi
N1 - Funding Information:
This work was partly supported by JSPS KAKENHI Grant Number 26460248.
Publisher Copyright:
© 2015 Royal Pharmaceutical Society.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Objectives Oxidative stress is known to be involved in the pathogenesis of chronic renal failure (CRF). In this study, the effect of cyclodextrins (CDs) on oxidative stress and CRF was investigated using 5/6 nephrectomized rats as model animals. Methods CRF model rats were divided into five groups and treated for 8 weeks as follows: control, α-CD, β-CD, γ-CD and 2-hydroxypropyl-β-CD (HP-β-CD). Blood was collected from the rats after 4 and 8 weeks for an analysis of renal function and oxidative stress tests were carried out. Key findings An oral administration of HP-β-CD over an 8-week period resulted in a significant decrease in serum indoxyl sulphate, creatinine and urea nitrogen levels, compared with the other CDs. The ingestion of HP-β-CD also resulted in an increase in antioxidant potential, compared with the other CDs. In in vitro studies, the interaction of HP-β-CD with a uremic toxin, indole molecule, was much higher than that for the other CDs, as evidenced by Proton nuclear magnetic resonance (1H NMR) measurements. Conclusions These results suggest that the ingestion of HP-β-CD might result in a significant reduction in the levels of pro-oxidants in the gastrointestinal tract, such as uremic toxins, thereby inhibiting the subsequent development of oxidative stress in the systemic circulation.
AB - Objectives Oxidative stress is known to be involved in the pathogenesis of chronic renal failure (CRF). In this study, the effect of cyclodextrins (CDs) on oxidative stress and CRF was investigated using 5/6 nephrectomized rats as model animals. Methods CRF model rats were divided into five groups and treated for 8 weeks as follows: control, α-CD, β-CD, γ-CD and 2-hydroxypropyl-β-CD (HP-β-CD). Blood was collected from the rats after 4 and 8 weeks for an analysis of renal function and oxidative stress tests were carried out. Key findings An oral administration of HP-β-CD over an 8-week period resulted in a significant decrease in serum indoxyl sulphate, creatinine and urea nitrogen levels, compared with the other CDs. The ingestion of HP-β-CD also resulted in an increase in antioxidant potential, compared with the other CDs. In in vitro studies, the interaction of HP-β-CD with a uremic toxin, indole molecule, was much higher than that for the other CDs, as evidenced by Proton nuclear magnetic resonance (1H NMR) measurements. Conclusions These results suggest that the ingestion of HP-β-CD might result in a significant reduction in the levels of pro-oxidants in the gastrointestinal tract, such as uremic toxins, thereby inhibiting the subsequent development of oxidative stress in the systemic circulation.
KW - 2-hydroxypropyl-β-cyclodextrin
KW - chronic renal failure
KW - oxidative stress
KW - uremic toxins
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U2 - 10.1111/jphp.12446
DO - 10.1111/jphp.12446
M3 - Article
C2 - 26058311
AN - SCOPUS:84930707364
SN - 0022-3573
VL - 68
SP - 608
EP - 614
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
IS - 5
ER -