Cyclophosphamide Inhibits PI3K/AKT/mTOR Signaling Pathway in Mice Kidneys

Abstract

Cyclophosphamide (CTX), also known as cytophosphane among other, is a medication used as chemotherapy and to suppress the immune system. The PI3K/AKT/mTOR pathway is involved in the regulation of diverse cellular functions, including cell growth, protein synthesis, cell cycle regulation, glucose metabolism, and motility. In our study eight weeks old C57BL/6 female mice were divided into 3 groups as control (C), sham (S) and experimental group. The experimental group has been established with CTX treatment. No treatment was applied to the C group. The S group were given an equal amount of saline. CTX was administered intraperitoneally one every 2 days for 3 weeks; the first dose was 70 mg/kg, the ongoing doses were 30 mg/kg. At the end of 3 weeks mice were sacrificed and kidneys were taken for investigation. In order to show the effect of cyclophosphamide in kidney tissue, the tissues were stained via indirect immunohistochemistry with PI3K, AKT and mTOR primary antibodies. In our study, PI3K, AKT and mTOR expression levels were found to be significantly decreased in CTX-mediated mechanisms indicating that the mechanisms of CTX might involve in the inhibition of PI3K/AKT/mTOR signaling pathway.

Protective effect of alogliptin against cyclophosphamide-induced lung toxicity in rats: Impact on PI3K/Akt/FoxO1 pathway and downstream inflammatory cascades

“…Multiple vacuolations (V) can be observed FoxO1. In accordance with our results, the study of Albayrak et al reported the repression of PI3K, Akt expression in the renal tissues of mice cured with CP (Albayrak et al 2018). Moreover, earlier studies have clarified the repressive effect of the anticancer medications on the PI3K/Akt axis mediating oxidative stress occurring with these drugs (Zhu et al 2009;Sun et al 2014a, b).…”

<p>Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats</p>

“… 63 , 64 The current study showed the downregulation of PI3K, Akt and mTOR expression in the heart of rats administered with CP. In accordance, the study of Albayrak et al 65 demonstrated the downregulation of PI3K, Akt and mTOR expression in the kidney of mice received CP every 2 days for 3 consecutive weeks. Given the role of the PI3K/AKT/mTOR pathway in maintenance of the cardiac structure and function and its suppression by CP, it would be intriguing to know whether the modulation of this pathway is involved in the cardioprotective effects of AV and ED.…”

Acetovanillone prevents cyclophosphamide‐induced acute lung injury by modulating PI3K/Akt/mTOR and Nrf2 signaling in rats

“…This notion is supported by the studies showing the inhibitory effect of the anticancer drug doxorubicin on the PI3K/Akt/mTOR pathway in cardiomyocytes (Lee et al, 2015; Zhu et al, 2009). In addition, PI3K, Akt, and mTOR expression was downregulated in the kidney of mice received CP for three consecutive weeks (Albayrak, Sonmez, Akogullari, & Uluer, 2018). Oral supplementation of AV upregulated PI3K, Akt, and mTOR in the lung of CP‐intoxicated rats, pointing to the involvement of PI3K/Akt/mTOR signaling in the protective effect of AV against CP‐induced AKI.…”