Rifaximin, a pregnane X receptor (PXR) activator regulates apoptosis in a murine model of breast cancer

利福昔明是一种孕烷 X 受体 (PXR) 激活剂,可调节小鼠乳腺癌模型中的细胞凋亡

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作者:Swetlana Gautam, Priyanka Singh, Manjari Singh, Subhadeep Roy, Jitendra K Rawat, Rajnish K Yadav, Uma Devi, Pushpraj S Gupta, Shubhini A Saraf, Gaurav Kaithwas

Abstract

The present study was proposed to investigate the effect of rifaximin (RFX) on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. Animals were randomized and divided among four groups of six animals each. Group I (control 0.9% normal saline, 3 ml kg-1, p.o.); Group II (toxic control, MNU 47 mg kg-1, i.v.); Group III (RFX, 25 mg kg-1, p.o.); Group IV (RFX, 50 mg kg-1, p.o.). Toxicity was induced by single i.v. injection of MNU. MNU treatment was evident with increased alveolar bud count, differentiation score, up-regulated inflammatory enzyme markers (COX, LOX, NO and H2S) and oxidative stress markers (TBAR's, protein carbonyl, SOD, catalase and Ach). The mammary gland surface architecture was studied using SEM, carmine staining and H&E staining. The treatment with RFX elicited noticeable restoration of the overall histological architecture in the experimental animals similar to the control. In the MNU treated toxic group, the levels of oxidative stress markers significantly increased in comparison to the control, which was subsequently restored after RFX treatment. Furthermore, RFX up regulated the levels of caspase 3 and caspase 8, when compared to the MNU treated animals. MNU associated toxicity was also ascertained, when determined for UCHL-1, COX, NF-κBp65, BAD, and BCL-xl expression, while RFX demonstrated modulation of the same.

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