Rapamycin and 3-methyladenine modulated autophagy markers and endocrine function in cisplatin-induced experimental cardiotoxicity, suggesting potential to mitigate cisplatin toxicity.
Does Rapamycin or 3-methyladenine modulate cisplatin-induced cardiotoxicity and autophagy in an experimental model?
Autophagy modulators such as rapamycin and 3-methyladenine can alter the endocrine and autophagic disruptions caused by cisplatin-induced cardiotoxicity.
In this study, we evaluated how cisplatin cardiotoxicity affects the histological and endocrine functions of the heart and autophagy while using Rapamycin(Rapa) and 3-methyladenine(3-MA) as autophagy activators and inhibitors. Control, Cisplatin (Cis), 3-methyladenine + Cisplatin (3-MA + Cis) and Rapamycin + Cisplatin (Rapa + Cis). Rapa and 3-MA were administered for 15 days, while a single dose of cisplatin was administered on the 7th day. Natriuretic peptide receptor-A(NPR-A), receptor-B(NPR-B) and biochemically atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP) levels were evaluated in heart tissue. Cis caused a statistically significant increase in NPR-A and NPR-B expression, as well as ANP and BNP levels. However, the levels of Beclin-1 and LC3B were not statistically significant. Rapa was more effective than 3-MA + Cis on NPR-A and NPR-B expressions, but did not show the same effect on ANP and NT-proBNP levels. Cis caused an increase in Beclin-1 and LC3B levels, while a decrease was observed in both 3-MA + Cis and Rapa + Cis groups. Our results revealed that Cis cardiotoxicity disrupts autophagy and endocrine function of the heart. It was concluded that by continuing the activator and inhibitor substances after Cis application, more effective results can be obtained in Beclin-1 expression than LC3B expression and that they can be effective in eliminating the toxicity of Cis.
Karabulut et al. (Fri,) conducted a other in Cisplatin-induced experimental cardiotoxicity. Rapamycin and 3-methyladenine vs. Control and Cisplatin alone was evaluated on Histological and endocrine functions of the heart and autophagy markers (NPR-A, NPR-B, ANP, BNP, Beclin-1, LC3B). Rapamycin and 3-methyladenine modulated autophagy markers and endocrine function in cisplatin-induced experimental cardiotoxicity, suggesting potential to mitigate cisplatin toxicity.