Telluric Acid Ameliorates Endotoxemic Kidney Injury in Mice: Involvement of TLR4, Nrf2, and PI3K/Akt Signaling Pathways

Document Type

Article

Publication Date

10-1-2017

Abstract

© 2017, Springer Science+Business Media, LLC. Being one of the most abundant trace elements in the human body, the therapeutic potential of tellurium-based compounds has been a target of interest. Recent reports denoted their redox-modulating and anti-inflammatory activities in experimental endotoxemia. However, their potential nephroprotective effect against endotoxemic kidney injury is yet to be elucidated. This study investigated the possible renoprotective effect of telluric acid (TEL) against lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice, targeting toll-like receptor 4 (TLR4), phosphoinositide 3-kinase (PI3K)/Akt, and nuclear factor-erythroid 2-related factor-2 (Nrf2) pathways as possible mechanistic contributors to TEL’s effect. AKI was induced by LPS (2 mg/kg). TEL (60 μg/kg; i.p.) was administered once daily for seven consecutive days before LPS injection. Pretreatment with TEL alleviated LPS-induced AKI as evidenced by the hampered serum levels of creatinine and cystatin C. TEL also opposed LPS-induced elevation in renal kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, nuclear factor-kappa B p65, interleukin-1β, and thiobarbituric acid-reactive substance contents. This was accompanied by a replenishment of renal glutathione, transcriptional upregulation of Nrf2, enhancement of heme oxygenase-1 activity, and a marked upregulation of phospho-PI3K and phospho-Akt protein expressions. Histopathological findings corroborated with the amendment of biochemical parameters. In view of these findings, we may conclude that TEL pretreatment purveyed novel nephroprotective effects against endotoxemic kidney injury, which might be partly attributed to the modulation of TLR4, PI3K/Akt, and Nrf2 signaling pathways and may hence provide a valuable asset for the management of endotoxemic renal complications.

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