Abstract
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.
Highlights
Chemotherapeutic drugs are broadly used against various kinds of cancer and their clinical use is associated with the occurrence of unfavorable side effects including many organ toxicities [1].One of these drugs is methotrexate (MTX) which is a folate antagonist used to treat oncologic and non-oncologic conditions like psoriasis and rheumatoid [2]
Effect on Renal TGF-β mRNA Expression In Figure 2, a marked upregulation of TGF-β mRNA level in renal tissue by 1.8-fold was reported in the MTX group compared to the NC group
Administration of Ginkgo biloba extract (GB) resulted in a notable downregulation of renal TGF-β mRNA expression by 50.3% when compared with the MTX group (p < 0.05)
Summary
Chemotherapeutic drugs are broadly used against various kinds of cancer and their clinical use is associated with the occurrence of unfavorable side effects including many organ toxicities [1]. One of these drugs is methotrexate (MTX) which is a folate antagonist used to treat oncologic and non-oncologic conditions like psoriasis and rheumatoid [2]. The majority of MTX is excreted through the kidney, nephrotoxicity is considered a strong reason which limited its use [3]. The pathogenesis of MTX-induced toxicity involved oxidative stress which played a crucial task in triggering inflammation and apoptosis processes [2,4,5,6].
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