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- Title
D-Pinitol alleviates cyclosporine A-induced renal tubulointerstitial fibrosis via activating Sirt1 and Nrf2 antioxidant pathways.
- Authors
Koh, Eun Sil; Kim, Soojeong; Kim, Minyoung; Hong, Yu Ah; Shin, Seok Joon; Park, Cheol Whee; Chang, Yoon Sik; Chung, Sungjin; Kim, Ho-Shik
- Abstract
Although the mechanism of cyclosporine A (CsA)-induced renal injury remains to be fully elucidated, accumulating evidence suggests that oxidative stress is critical in producing CsA-induced structural and functional renal impairment. The present study investigated the effect of D-pinitol, a cyclitol present in soybean, on chronic CsA nephropathy. Male ICR mice were treated with vehicle, CsA (30 mg/kg/day), D-pinitol (50 mg/kg/day) or a combination of CsA and D-pinitol for 28 days. To assess which pathway responding to oxidative stress is augmented by D-pinitol, the expression levels of several antioxidant enzymes and their possible regulators were measured. Treatment with D-pinitol significantly suppressed the increase of serum creatinine and decrease of urine osmolality, compared with the CsA control group. Histological examination of Masson's trichrome- and α-smooth muscle actin-stained renal tissue demonstrated that the CsA-induced tubulointerstitial fibrosis and inflammation were attenuated by D-pinitol. Following the administration of D-pinitol, there were increased expression levels of heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, superoxide dismutase 1 and catalase in CsA-treated kidneys. In addition, D-pinitol increased the level of sirtuin 1 (Sirt1), and the total and nuclear expression levels of nuclear erythroid factor 2-related factor 2 (Nrf2), suggesting that activation of the Sirt1 and Nrf2 pathways may induce the cellular antioxi dant system against CsA-induced nephropathy. Collectively, these data suggested that D-pinitol may protect the kidney from CsA-induced fibrosis, and that this renoprotective effect of D-pinitol was due to the inhibition of oxidative stress through the activation of Sirt1 and Nrf2, and the subsequent enhancement of antioxidant enzymes.
- Publication
International Journal of Molecular Medicine, 2018, Vol 41, Issue 4, p1826
- ISSN
1107-3756
- Publication type
Article
- DOI
10.3892/ijmm.2018.3408