Mohamed, A. F., M. M. Safar, H. F. Zaki, and H. M. Sayed, "Telluric Acid Ameliorates Endotoxemic Kidney Injury in Mice: Involvement of TLR4, Nrf2, and PI3K/Akt Signaling Pathways.", Inflammation, vol. 40, issue 5, pp. 1742-1752, 2017 Oct. 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.

Mohamed, A. F., M. F. El-Yamany, F. A. El-Batrawy, and M. T. Abdel-Aziz, "JNJ7777120 Ameliorates Inflammatory and Oxidative Manifestations in a Murine Model of Contact Hypersensitivity via Modulation of TLR and Nrf2 Signaling.", Inflammation, vol. 41, issue 2, pp. 378-389, 2018 Mar. Abstract

JNJ7777120, a histamine H4 receptor antagonist, was shown to be effective in different experimental settings of allergic inflammation, including contact hypersensitivity. Toll-like receptors (TLRs) are thought to function as a link between innate and adaptive immune responses to various haptens. Here, we studied the suppression of TLR signaling as a possible mechanism by which JNJ7777120 exerts its anti-inflammatory effects against the chemical hapten, fluorescein isothiocyanate (FITC). The potential anti-oxidant effect of JNJ7777120 in this model was also examined. Mice subjected to FITC sensitization and challenge showed significantly elevated plasma immunoglobulin E (IgE) level, ear interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid reactive substance (TBARS) contents as well as increased myeloid differentiation factor 88 (MyD88) gene expression, nuclear factor-kappa B p65 (NF-κB p65), and phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) protein expression. This was accompanied by enhanced ear myeloperoxidase (MPO) and eosinophil peroxidase (EPO) activities as well as diminished glutathione (GSH) content and superoxide dismutase (SOD) activity. JNJ7777120 treatment perceivably reversed these effects, denoting profound anti-inflammatory and anti-oxidant character of JNJ7777120 which was confirmed by its mitigation of FITC-induced pathological changes in mouse ear. JNJ7777120 additionally enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), providing a novel mechanism by which JNJ7777120 functions as an anti-oxidant in this model. To conclude, JNJ7777120 afforded a remarkable amendment of FITC skin insult by virtue of its anti-inflammatory and anti-oxidant effects; the mechanistic basis of these effects may include modulation of TLR and Nrf2 pathways.

aziz, M. A. T., F. A. El-Batrawy, M. F. El-yamany, and A. F. Mohamed, A study of the anti-inflammatory effect of histamine H1 and H4 receptor antagonists on dermatitis in mice, , 2015.