Doxorubicin and Doxorubicin-loaded Nanoliposome Triggers Hepatocyte Cells Senescence through Accumulation of Inflammatory Factors and Activation of P53
نویسندگان
چکیده مقاله:
Background and purpose: Induction of cellular senescence is indicative of new strategy to prevent abnormal proliferation of cancer cells. Doxorubicin (DOX) is gaining attention for its neoplasia suppressive and inhibitory properties, but its clinical utility is limited due to irreversible effects on non-target cells/tissues. In this way, nanoliposomal structures were developed in drug delivery systems with minimal systemic side effects. The biological role of doxorubicin-loaded nanoliposome (NLDX) in inflammation, a prerequisite for the onset of senescence, is unclear. This study was designed to evaluate the function of P53 and senescence-associated inflammatory markers during NLDX clearance in normal tissue of the liver. Materials and methods: This experimental study included three groups of Wistar rats; DOX (0.75, 0.5, and 0.1 mg/kg/BW) and LDOX (0.1, 0.05, 0.025 mg/kg/BW) groups, and a control group. Liver tissues were studied for inflammatory markers evaluation and Real-Time PCR was performed to investigate the level of P53 expression. Results: Data showed that NLDX at 0.1 mg/kg/BW could significantly induce senescence in rat liver tissue by remarkable increase in expression level of P53 (P<0.05) and senescence-related inflammatory markers, including TNF-α, NF-κB, interleukin -1, and interleukin-6 compared with a similar dose of DX (P<0.01). Conclusion: This research provides sufficient evidence of increased senescence in rat liver tissue caused by NLDX compared with DOX during liver excretion.
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15 صفحه اولDoxorubicin pharmacokinetics in lymphoma patients treated with doxorubicin-loaded eythrocytes.
Doxorubicin-loaded erythrocytes (DLE) were administrated to 15 lymphoma patients. Antibiotic peak concentration in blood decreased by 55%, doxorubicin circulated several times longer, and the area under the concentration-time curve increased 5 times if compared with standard doxorubicin administration. The DLE was well tolerated by patients.
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عنوان ژورنال
دوره 31 شماره 205
صفحات 17- 28
تاریخ انتشار 2022-02
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