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

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Abstract

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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  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt

    Ahmed F. Mohamed, Marwa M. Safar, Hala F. Zaki & Helmy M. Sayed

  2. Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt, Suez Desert Road, P.O. Box 43, El Sherouk City, Cairo, 11837, Egypt

    Marwa M. Safar

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All animal experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996).

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Mohamed, A.F., Safar, M.M., Zaki, H.F. et al. Telluric Acid Ameliorates Endotoxemic Kidney Injury in Mice: Involvement of TLR4, Nrf2, and PI3K/Akt Signaling Pathways. Inflammation 40, 1742–1752 (2017). https://doi.org/10.1007/s10753-017-0617-2

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