Sexual dimorphism of acute doxorubicin-induced nephrotoxicity in C57Bl/6 mice

PloS One
Marianne K O GrantBeshay N M Zordoky

Abstract

Doxorubicin (DOX) is a chemotherapeutic agent that has been reported to cause nephrotoxicity in rodent models and to a lesser degree in cancer patients. Female rodents have been shown to be protected against several features of DOX-induced nephrotoxicity. Nevertheless, the underlying mechanisms of this sexual dimorphism are not fully elucidated. Therefore, in the current study, we investigated the sex and time-dependent changes in pathological lesions as well as apoptotic and fibrotic markers in response to acute DOX-induced nephrotoxicity. We also determined the effect of acute DOX treatment on the renal expression of the sexually dimorphic enzyme, soluble epoxide hydrolase (sEH), since inhibition of sEH has been shown to protect against DOX-induced nephrotoxicity. Acute DOX-induced nephrotoxicity was induced by a single intra-peritoneal injection of 20 mg/kg DOX to male and female adult C57Bl/6 mice. The kidneys were isolated 1, 3 and 6 days after DOX administration. Histopathology assessment, gene expression of the apoptotic marker, BAX, protein expression of the fibrotic marker, transforming growth factor-β (TGF-β), and gene and protein expression of sEH were assessed. DOX administration caused more severe pathological lesi...Continue Reading

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Citations

Feb 23, 2020·International Journal of Molecular Sciences·Marianne K O GrantBeshay N Zordoky
Feb 7, 2021·Basic & Clinical Pharmacology & Toxicology·Ali A Shati, Attalla F El-Kott
Aug 10, 2021·Tissue & Cell·Ghadha Ibrahim Fouad, Kawkab A Ahmed

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Methods Mentioned

BETA
Assay
protein assay
electrophoresis
PCR

Software Mentioned

GraphPad Prism
ImageJ

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