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Ginkgo Biloba Extract Alleviates Methotrexate-Induced Renal Injury: New Impact on PI3K/Akt/mTOR Signaling and MALAT1 Expression

1
Emergency Hospital, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
2
Chemistry Department, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia
3
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 691; https://doi.org/10.3390/biom9110691
Received: 27 September 2019 / Revised: 28 October 2019 / Accepted: 2 November 2019 / Published: 3 November 2019
Renal injury induced by the chemotherapeutic agent methotrexate (MTX) is a serious adverse effect that has limited its use in the treatment of various clinical conditions. The antioxidant activity of Ginkgo biloba extract (GB) was reported to mitigate renal injury induced by MTX. Our research was conducted to examine the nephroprotective role of GB versus MTX-induced renal injury for the first time through its impact on the regulation of phosphatidylinositol 3-kinase/protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling together with the renal level of TGF-β mRNA and long non-coding RNA-metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) expression. A group of adult rats was intraperitoneally (ip) injected with MTX 20 mg/kg as a single dose to induce kidney injury (MTX group). The other group of rats was orally administered with GB 60 mg/kg every day for 10 days (GB+ MTX group). The MTX increased the serum creatinine and urea levels, renal TGF-β mRNA and MALAT1 expression, in addition to dysregulation of the PI3K/Akt/mTOR signaling when compared with normal control rats that received saline only (NC group). Moreover, renal damage was reported histopathologically in the MTX group. The GB ameliorated the renal injury induced by MTX and reversed the changes of these biochemical analyses. The involvement of PI3K/Akt/mTOR signaling and downregulation of TGF-β mRNA and MALAT1 renal expressions were firstly reported in the nephroprotective molecular mechanism of GB versus MTX-induced renal injury.
Keywords: Methotrexate; nephrotoxicity; Ginkgo biloba extract; PI3K/Akt/mTOR Methotrexate; nephrotoxicity; Ginkgo biloba extract; PI3K/Akt/mTOR
MDPI and ACS Style

Sherif, I.O.; Al-Shaalan, N.H.; Sabry, D. Ginkgo Biloba Extract Alleviates Methotrexate-Induced Renal Injury: New Impact on PI3K/Akt/mTOR Signaling and MALAT1 Expression. Biomolecules 2019, 9, 691.

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