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Issue 5, 2018
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Camel milk attenuates methotrexate-induced kidney injury via activation of PI3K/Akt/eNOS signaling and intervention with oxidative aberrations

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Abstract

Methotrexate (MTX) is a classical chemotherapeutic agent with nephrotoxicity as the most disturbing adverse effect. So far, its underlying molecular mechanisms, particularly PI3K/Akt/eNOS transduction, are inadequately explored. Several antioxidant modalities have been characterized to ameliorate MTX-induced renal injury. In this regard, Camel milk (CM) is a natural product with recognized antioxidant and anti-inflammatory features. Thus, the current study aimed to investigate the potential ameliorating effects of CM in MTX-induced kidney injury in rats. Renal tissues were studied in terms of renal injury markers, histopathology, oxidative stress, apoptosis and PI3K/Akt/eNOS signaling. CM was orally administered (10 ml kg−1) and the renal injury was induced by a single i.p. injection of MTX (20 mg kg−1). Interestingly, CM dose-dependently attenuated MTX-triggered increase of BUN and serum creatinine and renal Kim-1 expression and mitigated the renal histopathological changes. CM counteracted renal oxidative stress as manifested by lowering of lipid peroxides, restoration of NOX-1 levels and augmentation of the antioxidant defenses e.g., GSH, SOD, GPx and total antioxidant capacity. With respect to apoptosis, CM curbed the cleavage of PARP and caspase-3, downregulated p53, Bax and Cyt C proapoptotic signals and enhanced Bcl-2 and PCNA levels. In the same context, CM activated the prosurvival PI3K/Akt/eNOS pathway via enhancing PI3K p110, phospho-Akt and phospho-eNOS levels. Equally important, CM preconditioning did not interfere with MTX cytotoxicity in TK-10 or PC-3 cancer cells. Together, the current findings demonstrate, for the first time, the renoprotective effects of CM in MTX-induced kidney injury via activation of PI3K/Akt/eNOS signaling and combating oxidative stress and apoptosis.

Graphical abstract: Camel milk attenuates methotrexate-induced kidney injury via activation of PI3K/Akt/eNOS signaling and intervention with oxidative aberrations

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Article information


Submitted
21 Jan 2018
Accepted
06 Apr 2018
First published
18 Apr 2018

Food Funct., 2018,9, 2661-2672
Article type
Paper

Camel milk attenuates methotrexate-induced kidney injury via activation of PI3K/Akt/eNOS signaling and intervention with oxidative aberrations

H. H. Arab, S. A. Salama and I. A. Maghrabi, Food Funct., 2018, 9, 2661
DOI: 10.1039/C8FO00131F

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