Low concentration of rutin treatment might alleviate the cardiotoxicity effect of pirarubicin on cardiomyocytes via activation of PI3K/AKT/mTOR signaling pathway

Abstract

Cancer is the leading cause of deaths around the world, especially in low- and middle- income countries. Pirarubicin (THP) is an effective drug for treatment of cancer, however, there still exists cardiotoxic effects of THP. Rutin is a kind of antioxidative compound extracted from plants, and might be a protective compound for cardiomyocytes. Phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is critical for cellular survival, proliferation and metabolism, and thus we speculated rutin might perform a protective role in cardiomyocytes via PI3K/AKT/mTOR signaling pathway. And in this experiment, we first established a cardiotoxicity model of THP in mice model and cell models, and then found that rutin treatment could increase the proliferation of cells at low concentration. Then we explored the possible mechanism of the protective effect of rutin using Western blotting, quantitative polymerase chain reaction (qPCR) and ELISA methods, and found that the activation of PI3K/AKT/mTOR/nuclear factor-κB (NF-κB) signaling pathway was increased, and expression of downstream molecules involved in antioxidative stress were also increased. We further noticed that concentration of angiogenesis promoting factors were also increased in medium of cultured cells. Thus, we speculated that rutin could increase the activation of PI3K/AKT/mTOR signaling pathway, further decrease the oxidative stress level via increasing the expression of antioxidative stress enzymes with the increasing concentration of angiogenesis promoting factors, resulting in the protective role in cardiomyocytes and cardiac function.

Rutin trihydrate attenuated cisplatin- induced cardiac toxicity in isolated perfused rat’s hearts

“…Cisplatin causes cardio-toxic effects by oxidative stress and decrease in antioxidant enzymes [11]. Rutin has been previously reported for bene cial protective effects against variety of drug induced toxicities including doxorubicin and cisplatin induced cardiac toxicity [12][13][14]. The protective effects of rutin trihydrate observed in our current study mostly likely occurred due to its profound anti-oxidant properties.…”

“…Increase in oxidative stress and decrease in antioxidant enzymes are linked with cardio-toxic effects of cisplatin [11]. Rutin has been reported for bene cial protective effects against variety of drug induced toxicities including doxorubicin and cisplatin induced cardiac toxicity and memory de cits [12][13][14].…”

Natural compounds against cytotoxic drug‐induced cardiotoxicity: A review on the involvement of PI3K/Akt signaling pathway

“…It has been reported that rutin can increase PI3K, Akt, and mTOR, and decrease NF‐κB expression. The involvement of rutin in cardiac function may be through activation of PI3K/Akt/mTOR and inhibition of the NF‐κB pathway [ 22 ] (Figure 3).…”

MicroRNA‐129‐1‐3p protects cardiomyocytes from pirarubicin‐induced apoptosis by down‐regulating the GRIN2D‐mediated Ca2+ signalling pathway

“…6,7 Thus, novel therapeutic agents that help combat THP-induced cardiotoxicity are required. 6,7 Thus, novel therapeutic agents that help combat THP-induced cardiotoxicity are required.…”

“…However, patients who receive THP treatment can still suffer significant cardiac injuries. 6,7 Thus, novel therapeutic agents that help combat THP-induced cardiotoxicity are required.…”